Comparative study of interictal PET and ictal SPECT in complex partial seizures

Objective – To compare the sensitivity of ictal ^99mTc-HMPAO single photon emission computed tomography (SPECT) with interictal ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in localization of the epileptogenic focus in patients with medically intractable complex partial seizures (MI-CPS). Material and methods – Retrospective analysis was performed on patients with MI-CPS who underwent anterior temporal lobectomy from January 1993 onwards when PET became available to us for clinical studies at the Indiana University Medical Center. There were 38 female and 29 male patients (total=67) with MI-CPS, 10 to 55.5 years of age (mean 31) and duration of their epilepsy from 1-46 years (mean 21). Interictal PET was evaluated for evidence of focal hypometabolism and ictal SPECT for focal perfusion abnormality (hyperperfusion or hypoperfusion) by visual analysis. Results – Both Ictal SPECT and interictal FDG-PET studies were obtained in 36 patients with MI-CPS. PET showed definite hypometabolism in 30 and questionable hypometabolism in an additional two patients. Ictal SPECT correctly localized the seizure focus in 27 patients by demonstrating ictal hyperperfusion whereas in one the hyperperfusion was falsely localized. In an additional seven patients the ictal SPECT provided probable localization by demonstrating ictal hypoperfusion in the appropriate temporal lobe. The sensitivity of ictal SPECT and interictal PET was 34/36 and 32/36, respectively, the difference was not statistically significant (χ²_y=0.18, DF=1, P=0.67). In six of the 36 patients the two tests were complementary to each other in providing localizing information. Conclusion – Ictal SPECT and interictal PET are equally sensitive and reliable techniques in localizing the epileptogenic focus in patients with MI-CPS. They play a critical role in providing localization in MRI negative patients allowing surgical resection to be undertaken in many without additional invasive electrographic monitoring.     

HIPDM-SPECT in patients with medically intractable complex partial seizures. Ictal study

Both interictal and ictal N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3,propanediamine -single photon emission computed tomography (HIPDM-SPECT) were performed in 16 patients with medically intractable complex partial seizures. Ictal HIPDM-SPECT localized epileptic foci in 13 of 14 patients with unilateral temporal focus and provided confirmative evidence of epileptic focus in 11 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci that had shown decreased rCP in a previous interictal study. Ictal HIPDM-SPECT in two patients with bitemporal foci showed more complicated patterns consisting of slightly increased rCP in bilateral multifocal regions. Ictal HIPDM-SPECT was particularly useful for investigating epileptic foci, and correlation with simultaneously recorded ictal electroencephalograms provided further insight for localizing epileptic foci.     

Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures

The efficacy and safety of felbamate monotherapy were evaluated in 52 patients with refractory partial seizures with or without secondary generalization in a double-blind, randomized, placebo-controlled trial. Each patient completed a routine evaluation for epilepsy surgery and was randomized to receive either felbamate, titrated to a maximum daily dose of 3600 mg over 2 days, or placebo during the 10-day, inpatient, treatment phase. An intent-to-treat analysis was performed on the data of all 52 patients who received study medication, while a separate efficacy analysis also was performed on the data of 43 evaluable patients, which excluded protocol violators. The endpoint of the trial was completing 10 days of treatment or the occurrence of a fourth seizure. The primary efficacy variable was the average daily seizure frequency during the treatment phase for each patient. For the intent-to-treat analysis based on all 52 patients who received study medications, the mean rank of the daily seizure frequency for patients treated with felbamate was 21.6 compared to 29.6 for patients treated with placebo (P = 0.065). In the analysis based on the 43 evaluable patients, the mean rank of the daily seizure frequency for felbamate-treated patients was 17.0 compared to 25.4 for placebo-treated patients. This difference was statistically significant (P = 0.032) in favor of felbamate. Seizure frequency was decreased by 89.5% compared to baseline in nine patients who completed 10 days of felbamate therapy. This study permitted the rapid determination of the anticonvulsant activity of felbamate and demonstrated that felbamate is effective as monotherapy for the treatment of partial seizures.     

Chronic epilepsy with complex partial seizures is not always medically intractable--a long-term observational study

OBJECTIVE: To study the prognosis of patients with complex partial seizures (CPS) with or without simple partial (SPS) and secondarily generalized tonic-clonic seizures (GTCS) and to analyze the factors related to the degree of medical responsiveness. MATERIAL AND METHODS: A total of 266 adult patients with CPS were included in a hospital based observational survey with a follow-up of 2 to 25 years. Clinical characteristics, seizure frequency, electroencephalography (EEG), cerebral computed tomography (CCT) and magnetic resonance imaging (MRI) findings were analyzed. Patients were categorized according to their degree of medical responsiveness into one of three groups: seizure free, improved control (>50% seizure reduction) and poor control. RESULTS: Mean age at follow-up was 44.7 years (SD 14.7, range 19-93). Mean age at seizure onset was 18.1 years (SD 14.7, median 15, range 1-79). Complete seizure control was achieved in 40%, improved seizure control in 36% and poor seizure control in 24%. Patients entered remission after a mean period of 15.7 years (SD 12.6, median 13, range 1-54) of active epilepsy. A third of all seizure-free patients were still in remission 6.1 years (SD 5.3, median 3.5, range 1-18) after discontinuation of antiepileptic drugs (AED). Patients with poor seizure control had a significantly younger age at onset (P<0.01), a higher initial seizure frequency (more than 3 per month) (P<0.01), abnormal neurological examination (P<0.01), and were more often mentally handicapped (P<0.01). Multiple logistic regression analysis revealed a high initial seizure frequency, mental handicap and an abnormal neurological examination as independent risk factors for poor seizure control. A positive family history, a history of febrile convulsions and/or psychosis, an abnormal EEG or MRI was not predictive of poor outcome. CONCLUSIONS: Not all patients with CPS were medically intractable. Seizure remission can be achieved after a long time of active epilepsy. Poor seizure control was associated with a high initial seizure frequency, mental handicap and abnormal neurological examination.     

Febrile seizures in patients with complex partial seizures

Febrile seizures occurred in 14 of 155 (9%) out-patients with complex partial seizures. Twelve patients had prolonged or recurrent febrile seizures, convulsive status epilepticus or a transient postictal neurological deficit. Febrile seizures were associated with perinatal abnormalities, an earlier onset of epilepsy and with a poor seizure control. Recurrent febrile seizures or those with complicating features are associated with an unfavourable therapeutic outcome in adult patients with complex partial seizures.     

Lorazepam: a controlled trial in patients with intractable partial complex seizures

Lorazepam was studied in a double-blind, placebo-controlled, crossover trial in eight patients with frequent partial complex seizures refractory to therapy with a combination of standard anticonvulsant drugs. Concomitant antiepileptic drugs were maintained at therapeutic serum levels throughout the study, and concentrations of lorazepam were monitored. Following an 8-week baseline observation, patients were randomly assigned to placebo or lorazepam (1 mg BID). The dose was increased biweekly until seizures stopped or unacceptable side effects occurred. Eight weeks later, patients were crossed over, and the same escalating dose paradigm was followed. When seizure frequency during the last 2 weeks of each treatment was compared, seven of eight patients had fewer seizures on lorazepam, and the eighth had decreased seizure duration (a significant difference: p less than 0.01, two-tailed sign test). Blood level data suggest a narrow therapeutic window, with seizure improvement occurring at concentrations of 20-30 ng/ml and side effects at greater than 33 ng/ml. Lorazepam appears to be a useful adjunct in refractory partial complex seizure therapy. It should not be stopped abruptly, as an increase in seizure frequency may result.     

Double-blind placebo-controlled evaluation of flunarizine as adjunct therapy in epilepsy with complex partial seizures

Flunarizine was compared to placebo in a double-blind cross-over trial of 2 16-week treatment periods separated by a 4-week wash-out period. The patients had epilepsy with complex partial seizures with or without secondary generalised seizures. Twenty-nine patients entered the trial, but 7 dropped out. Of the 22 patients completing the trial, 13 were women; the median was 39 years (range 15-58) and the median duration of epilepsy 23 years (range 4-55). There was no statistically significant difference between flunarizine 15 mg daily and placebo as adjunct therapy in total seizure frequency, neuropsychological tests, and patient's preferences. No interactions with concomitant antiepileptic drugs and no laboratory abnormalities were registered.     

Epileptiform EEG activities of the centromedian thalamic nuclei in patients with intractable partial motor, complex partial, and generalized seizures

Centromedian thalamic nuclei (CM) epileptiform EEG activities were recorded in patients with intractable partial motor, complex partial, and generalized seizures through implanted recording-stimulating electrodes, used for seizure control. CM epileptiform activities showed either little or no correlation to focal surface cortical and amygdaloid activities in patients with partial motor and complex partial seizures: CM paroxysmal discharges were correlated to focal epileptiform ictal activities only during the contraversive movements of partial motor and complex partial seizures. In contrast, CM epileptiform activities were consistently correlated to widespread surface cortical activities and clinical symptoms of fully developed nonconvulsive and convulsive tonic-clonic generalized seizures; i.e., unilateral CM double spike-wave complex discharges significantly preceded (p less than 0.001) the contralateral CM and bilateral surface cortical discharges and symptoms of nonconvulsive generalized seizures. Unilateral CM fast-slow-fast paroxysmal discharges significantly preceded (p less than 0.005) those of the contralateral CM and bilateral surface cortical regions and symptoms of the convulsive tonic-clonic generalized seizures. Individual spike-wave complexes from the frontal region preceded (p less than 0.001 and p less than 0.005) those at CM and other cortical regions during the nonconvulsive and clonic generalized attacks. No correlations between CM and cortical epileptiform activities were found, however, in the case of abortive, subclinical thalamocortical EEG discharges.     

The evaluation of patients with intractable complex partial seizures

Conceptual advantages, together with advances in both technique and technology, have considerably altered the approach to intractable epilepsy over the past two decades. Appropriate utilization of these advances allows our evaluation of patients with intractable seizures to be much more precise and specific than was once the case and allows us to improve considerably our ability to treat patients with intractable epilepsy. We propose an algorithm for the evaluation and treatment of patients with intractable complex partial seizures. Other forms of intractable epilepsy may benefit from similar diagnostic and therapeutic approaches.     

First Alfred Meyer Memorial Lecture. Epileptic brain damage: a consequence and a cause of seizures

Alfred Meyer and his colleagues were the first to report (1954–1956) that the most frequent pathology in tissue from patients with complex partial seizures successfully treated by anterior temporal lobectomy is mesial temporal sclerosis, and that the majority of patients with this lesion give a history of a prolonged seizure early in life. These observations have been repeatedly confirmed. Experimental data from animal models strongly supports the hypothesis that a prolonged generalized or limbic seizure in early life damages the hippocampus and other limbic structures, facilitating an epileptogenic process that, after a latent period, gives rise to spontaneous limbic seizures. Some mechanisms potentially contributing to this process have been identified.     

Surgical treatment of patients with low-grade astrocytomas and medically intractable seizures

OBJECTIVE: Low-grade astrocytomas can present with seizures that respond poorly to antiseizure medications, with a consequent reduction in the quality of life, because of both seizures and the medication's side-effects. We report our experience with operative treatment of such patients. SUBJECTS AND METHODS: Five patients (two children and three adults) with supratentorial low-grade astrocytomas associated with severe seizures were operated on. We followed the effects of the operation on post-operative neurological deficit, seizure frequency and the quality of life. RESULTS: No serious neurological complications followed the operations. The patients were followed for a median period of 12 months (6-46). Post-operatively, three of the patients became seizure-free, one experiences only auras, and one had a great reduction in seizure frequency and severity. All patients reported great improvement in their quality of life. CONCLUSION: Resections of low-grade astrocytomas in patients with medically intractable seizures are safe procedures that effectively control seizures in the majority of patients, resulting in significant improvement in the patients' quality of life.     

The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures

PURPOSE: We examined the association between seizure clustering and convulsive status epilepticus (SE) in patients with intractable complex partial seizures, to identify whether patients whose seizures typically cluster are at high risk for convulsive SE (CSE). METHODS: Seventy-six patients with intractable complex partial epilepsy who underwent presurgical evaluation in the Montefiore Epilepsy Management Unit from 1993 to 1997 were contacted and interviewed about typical seizure frequency and distribution and history of CSE. Seizure clustering was defined as three or more complex partial seizures within a 24-h period, with return to baseline between seizures. RESULTS: Of the 76 patients contacted, 21 (28%) had experienced at least one episode of CSE, and 36 (47%) typically experienced clustered seizures. SE occurred in 16 (44%) of 36 patients with clustered seizures, and in five (12.5%) of 40 patients with nonclustered seizures (p < 0.002). Of 53 patients with temporal lobe epilepsy, CSE occurred in 13 (50%) of 26 patients with clustered seizures, and four (14.8%) of 27 patients with nonclustered seizures (p < 0.006). CONCLUSIONS: Patients with intractable complex partial or localization-related epilepsy who typically experience seizure clustering are at a significantly higher risk for CSE than are patients with nonclustered seizures.     

发作期录像脑电监测在15例难治性颞叶癫痫患者术前定位中的价值

目的 探讨发作期录像脑电监测（IVEEG）在难治性非病变性颞叶癫痫（TLE）致痫源术前定位中的价值。方法 对15例药物难治性TLE患者术前定位资料及术后随诊情况进行分析。结果 所有患者在行长时间IVEEG监测中均捕获到临床发作。在15例患者中，有13例IVEEG显示出一侧起源的局灶爆发性节律性电活动，该放电侧均与最终切除侧相一致，且有11例患者术后效果较好。结论 IVEEG监测不仅有助于明确诊断及发作类型，更为重要的是对于大多数难治性非病变性TLE患者可提供较可靠的致痫源定侧信息。     

Ictus expectoratus: a sign of complex partial seizures usually of non-dominant temporal lobe origin

Spitting (or expectoration) is rarely seen with seizures. In Western society, spitting is a striking behavioral aberration. A 13-year-old child had intermittent agitated behavior, episodes of rage, spitting and confusion lasting up to 2 minutes. He stood up in church and told the preacher to 'shut up and sit down'. Epilepsy monitoring revealed spitting with polysharp and spike seizures resolved over the right temporal lobe. Magnetic resonance imaging revealed a right temporal lobe ganglioglioma. Spitting seizures resolved after resection. Ictal expectoration is rare. It may occur with epigastric aura, nausea, chewing, swallowing and fumbling. Literature review disclosed 17 cases, 12 of which arose from the non-dominant hemisphere. Most regressed with surgery and anticonvulsants.     

Interictal HM-PAO SPECT: a routine investigation in patients with medically intractable complex partial seizures?

Single photon emission computed tomography (SPECT) is increasingly being used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. As yet, few studies have been undertaken to establish the clinical associations of areas of reduced cerebral perfusion. Sixty-three consecutive patients (15 male, 48 female; median age 30 years, range 14-57 years) with medically intractable complex partial seizures (median/month 8, range 1-36) were investigated as outpatients. All had normal high resolution computerised X-ray tomography (CT) of brain. Twenty-seven (47%) exhibited significant perfusion defects on SPECT scanning with a rotating gamma camera system using Tc-99 HM-PAO. There were no significant differences between patients with normal and abnormal scans in terms of age at scanning or at onset of epilepsy or number of seizures. Patients with perfusion defects did, however, have longer median histories of epilepsy than those with normal scans (normal: 10 years, abnormal: 22 years; P = 0.01). Patients with abnormal scans were no more likely to have suffered febrile convulsions in early childhood. The correlation of abnormal SPECT scans with routine surface EEG recordings was poor with only 41% of cases showing clear agreement between the site of hypoperfusion and focal epileptic activity. It is not yet possible to predict clinically those patients who will exhibit perfusion defects on interictal TC-99 HM-PAO SPECT scanning.     

Epileptic seizures in a patient by immersing his right hand into hot water

We report on a 22-year-old assistant cook, presenting with seizures evoked by immersing his right hand into hot water of 40-46 degrees C. His seizure pattern consisted of either simple partial seizures of a tingling sensation arising in the right hand and marching to the right shoulder or a similar attack evolving to a complex partial seizure. Video-EEG monitoring recorded habitual seizures originating from the left centro-temporo-parietal region, compatible with lesions seen on brain magnetic resonance imaging. He responded well to antiepileptic drug treatment and wearing gloves while working in the kitchen. In this patient, hot water of 40-46 degrees C could maximally stimulate skin warm thermoreceptors in the right hand whereby afferent impulses subsequently activated the epileptogenic focus, adjacent to or in the sensory cortex, and elicited seizures.     

表现有立毛运动的复杂部分性癫痫(附3例报告及文献复习)

目的了解立毛运动性发作的病理生理、病因及临床特点。方法结合3例立毛运动性发作病例及文献复习(已报过21例)，探讨立毛运动性发作的特点。结果立毛运动性发作的最重要临床表现是反复的立毛运动，可能与右颞叶额叶(眶面皮层，运动前区)下丘脑和边缘系统学结构有关，脑电图(EEG)表现为非特异性异常，但是大多数病例有发作期发放或癫痫样波，视频监测脑电图(Video—EEG)对于评价其分型及发作期、发作间期变化有帮助。结论立毛运动性发作极罕见。但是注意结合病史，体检和EEG检查还是可以发现的。     

Memory for objects presented soon after intracarotid amobarbital sodium injections in patients with medically intractable complex partial seizures

We evaluated the abilities of 36 patients with intractable temporal lobe epilepsy and left hemisphere dominance for language to later recognize objects presented in the confusional phase after left intracarotid amobarbital injection. Eighteen of 24 patients with left, but only 4/12 with right, temporal lobe epilepsy recognized at least two-thirds of objects during a post-test. These results demonstrate that the initial muteness and apparent confusion after amobarbital injection do not prohibit the formation of new memories; this gives further support to the idea that consciousness can be retained despite transient disruption of function of the language-dominant hemisphere.