Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

Circadian patterns of pediatric seizures.

OBJECTIVE: To evaluate the relationship of sleep/wake and day/night pattern to various seizure subtypes and epilepsy localizations. METHODS: Charts of 380 consecutive pediatric patients with epilepsy undergoing video-EEG (V-EEG) over 2 years were reviewed for seizure semiology, EEG localization, occurrence during the day (6 am-6 pm) or night, during wakefulness and sleep, 3-hour time blocks throughout 24 hours, and various epilepsy localizations, and etiology. RESULTS: A total of 1,008 seizures were analyzed in 225 children (mean age 8.5 ± 5.7 years). Sleep and wakefulness predicted seizure semiology and localization more reliably than daytime and nighttime. Auras, gelastic, dyscognitive, atonic, hypomotor, and myoclonic seizures, and epileptic spasms occurred more often in wakefulness, while tonic, tonic-clonic, automotor, and hypermotor seizures occurred more frequently in sleep (p < 0.05). Clonic, atonic, myoclonic, and hypomotor seizures occurred more frequently during daytime. Hypermotor and automotor seizures occurred more frequently at night (p < 0.05). Generalized seizures (6 am-12 pm), temporal lobe seizures (9 pm-9 am), frontal lobe seizures (12 am-6 am), parietal lobe seizures (6 am-9 am), and occipital lobe seizures (9 am-noon and 3-6 pm) revealed specific circadian patterns (p < 0.05). In addition, generalized and temporal lobe seizures occurred more frequently in wakefulness, while frontal and parietal seizures occurred more frequently in sleep, independent of day or night pattern (p < 0.05). CONCLUSION: Sleep and wakefulness, as well as time of day and night, are important considerations in proper characterization of seizure types and epilepsy localization. These findings may contribute to a better understanding of the mechanisms of nonrandom distribution of seizures, and may provide information for individualized treatment options.

Successful surgery for epilepsy due to early brain lesions despite generalized EEG findings.

OBJECTIVE: To understand the role of epilepsy surgery in children with generalized or bilateral findings on preoperative scalp EEG. METHODS: From our pediatric epilepsy surgery series, we identified 50 patients in whom 30 to 100% of preoperative epileptiform discharges (ictal, interictal, or both) were generalized or contralateral to the side of surgery. RESULTS: All patients had severe refractory epilepsy and an epileptogenic lesion on brain MRI. Ninety percent of the lesions were congenital, perinatal, or acquired during infancy, predominantly malformations of cortical development (44%) or cystic encephalomalacia (40%). Age at surgery was 0.2 to 24 (median 7.7) years. Surgeries were hemispherectomy (64%) or lobar or multilobar resection. At last follow-up (median 24.0 months), 72% of patients were seizure-free, 16% had marked improvement with only brief episodes of staring or tonic stiffening, and 12% were not improved. The rate of seizure-free outcome was not significantly associated with age at seizure onset or surgery, presence of hemiparesis or focal clinical features during seizures, type of lesion, or surgery type. Postoperative seizure-free rate did not differ from that in a comparison group of similar patients who matched the study group except for their high percentage (70 to 100%) of ipsilateral ictal and interictal epileptiform discharges on preoperative EEG. CONCLUSIONS: Epilepsy surgery may be successful for selected children and adolescents with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG. The diffuse EEG expression may be due to an interaction between the early lesion and the developing brain.

[Suggestion for a new, patient-oriented epilepsy classification]. / Vorschlag für eine neue patientenorientierte Epilepsieklassifikation.

The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Postoperative seizures after extratemporal resections and hemispherectomy in pediatric epilepsy.

OBJECTIVES: To estimate frequency and risk factors for acute postoperative seizures (APOS) within the first week after extratemporal cortical resection (ETR) and hemispherectomy (HS) in children and to assess the predictive value of APOS on long-term seizure outcome in this group. METHODS: The authors conducted a retrospective analysis of children (< 18 years), who underwent ETR or HS for intractable epilepsy between 1995 and 2002. APOS features and seizure outcome after ETR or HS were obtained at 6, 12, and 24 months. Univariate logistic regression was used for risk factors of APOS and life table analysis and log rank tests for seizure outcome at 0 to 6, 6 to 12, and 12 to 24 months. RESULTS: Of 132 patients, 34 (26%) had APOS. APOS were more frequent after ETR (26/71) than HS (8/61) (p < 0.01). APOS, irrespective of their timing, number, semiology, or other perioperative complications, were an independent predictor of poor postoperative seizure outcome at 2 years (p < 0.001). The estimated odds of postoperative Engel class I outcome in the APOS vs non-APOS categories was 0.27 (73% less likely) for 0- to 6-month, 0.22 (78% less likely) for 6- to 12-month, and 0.13 (87% less likely) for the 12- to 24-month intervals. CONCLUSIONS: Acute postoperative seizures (APOS) occur in 26% children, and the risk is higher after extratemporal cortical resection than hemispherectomy. APOS predict a poor postoperative seizure outcome at 6, 12, and 24 months. This study is useful for counseling families after epilepsy surgery. It also suggests that APOS may not be discounted as "benign" in research studies that evaluate seizure outcomes after epilepsy surgery.

Identification of candidates for epilepsy surgery in patients with tuberous sclerosis.

The authors reviewed preoperative MRI and EEG findings in relation to postsurgical outcome in 17 patients with refractory epilepsy due to tuberous sclerosis complex (TSC). Resecting concordant MRI (main tuber) and EEG abnormalities offered seizure freedom (8/9, 89%; median follow-up 25 months) comparable to other focal etiologies. Patients with nonconcordant MRI and EEG findings did less well (3/8, 38%, seizure free; p = 0.027, OR = 13).

Seizure outcome after epilepsy surgery in patients with normal preoperative MRI.

OBJECTIVE: To determine outcome after epilepsy surgery in patients with normal preoperative magnetic resonance imaging (MRI). METHODS: 24 adult and paediatric patients with normal preoperative MRIs were studied. They underwent epilepsy surgery between 1994 and 2001 and had at least one year of follow up. RESULTS: At the most recent follow up, nine patients (37%) were seizure-free and 18 (75%) had at least a 90% reduction in seizure frequency with weekly or monthly seizures. Seizure freedom was not significantly different after resections in frontal (5/9) or temporal regions (4/13) (p = 0.24, Fisher's exact test), or among patients with or without localising features on EEG, PET, or ictal SPECT. Subdural grids, used in 15 of 24 patients, helped tailor resections but were not associated with differences in outcome. Histopathology showed cortical dysplasia in 10 patients (42%), non-specific findings in 13 (54%), and hippocampal sclerosis in one (4%). Cortical dysplasia was seen in seven patients with frontal resection (78%) and non-specific findings in nine (69%) with temporal resection. Seizure outcome did not differ on the basis of location of resection or histopathology. CONCLUSIONS: While these results were less favourable than expected for patients with focal epileptogenic lesions seen on MRI, they represented worthwhile improvement for this patient population with high preoperative seizure burden. In this highly selected group, no single test or combination of tests further predicted postoperative seizure outcome.

Resective surgery to treat refractory status epilepticus in children with focal epileptogenesis.

Prolonged high-dose suppressive therapy (HDST) is a mainstay in the management of refractory status epilepticus (RSE), albeit with high morbidity and mortality. The authors studied 10 patients who were carefully selected for epilepsy surgery after failing prolonged (>2 weeks) HDST. Status epilepticus was stopped acutely in all of them with no mortality and no substantial morbidity. At follow-up (median 7 months), 7 (70%) of 10 patients were seizure free, and 3 (30%) of 10 had significant improvement in their epilepsy.

Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society.

OBJECTIVE: To determine the current best practice for treatment of infantile spasms in children. METHODS: Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. RESULTS: Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. CONCLUSIONS: ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective.

Aphasia after hemispherectomy in an adult with early onset epilepsy and hemiplegia.

A 55 year old left handed man with left hemisphere subcortical encephalomalacia, seizures, language impairment, and right hemiparesis from a motor vehicle accident at age five was evaluated for epilepsy surgery. The patient continued to speak and followed commands during a left intracarotid amobarbital test (IAT). Left functional hemispherectomy resulted in expressive aphasia. Based on postoperative outcome, language was bilateral. The injury after primary development of language function, the predominantly subcortical lesion, and the late timing of surgical intervention well past development and plasticity may have been factors in the emergence of postoperative aphasia.

Intractable epilepsy in vascular congenital hemiparesis: clinical features and surgical options.

Forty-one patients with vascular congenital hemiplegia and intractable epilepsy were reviewed. Most had severe hemiparesis, mental retardation, porencephaly, and focal epilepsy. Thirty-three were considered surgical candidates and 25 underwent surgery. Seizure freedom and significant seizure reduction were achieved in 12 of 13 patients after functional hemispherectomy, 4 of 6 after temporal lobectomy, 2 of 2 with extratemporal focal resections, 1 of 3 with corpus callosotomy, and 1 with porencephalic cyst drainage.

Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX.

Subcortical band heterotopia (SBH) is seen predominantly in females, resulting from mutations in the X-linked doublecortin (DCX) gene, and can present with mild mental retardation and epilepsy. Males carrying DCX mutations usually demonstrate lissencephaly and are clinically much more severely affected. This article reports two cases of males with SBH indistinguishable from the female phenotype, both resulting from somatic mosaicism for DCX mutation.

Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

Efficacy of the ketogenic diet in focal versus generalized seizures.

Most reports of the ketogenic diet have focused on its efficacy for generalized seizures. Few data are available regarding its effect on focal seizures. We retrospectively studied patients (mean = 7.5 years of age) with medically intractable epilepsy treated by the ketogenic diet. The predominant seizure types in each patient were classified as generalized (100 patients) or focal (34 patients) based on ictal electroencephalograms (EEGs) or seizure semiology and interictal EEG. A seizure reduction of more than 50% compared with baseline was seen in nine patients (27%) with focal seizures and 46 patients (46%) with generalized seizures at 3 months, in 10 patients (30%) with focal seizures and 46 patients (46%) with generalized seizures at 6 months, and in eight patients (24%) with focal seizures and 42 patients (42%) with generalized seizures at 12 months. Differences were not significant. Outcome tended to be better in patients younger than 12 years of age compared with the older age group, but the difference was significant at 6 months only. Our results suggest that some patients with intractable focal epilepsy may respond favorably to the ketogenic diet and that this option should be considered if epilepsy surgery is not possible.

Fluid-attenuated inversion recovery: correlations of hippocampal cell densities with signal abnormalities.

BACKGROUND: Hippocampal sclerosis (HS) is characterized by hippocampal atrophy and increased signal on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. OBJECTIVE: To quantitate cell loss and compare it with signal abnormalities on FLAIR images. METHODS: Thirty-one patients with temporal lobe resection, pathologically proven HS, and Engel class I and II outcome were included: 20 with HS only and 11 with HS associated with pathologically proven cortical dysplasia (dual pathology). The signal intensity on FLAIR was rated as present or absent in the hippocampus and correlated with the neuronal losses in the hippocampus. RESULTS: FLAIR signal increases were present in 77% (24/31) of all patients studied. In patients with isolated HS, 90% (18/20) had ipsilateral signal increases, but in patients with dual pathology, only 55% (6/11; p < 0.02) showed FLAIR signal increase. Hippocampal cell losses were significantly higher in the isolated HS group. The average cell loss in patients with FLAIR signal abnormalities was 64.8 +/- 8.0% as compared with only 32.7 +/- 5.1% in patients with no FLAIR signal abnormalities. There was a significant positive correlation between the presence of signal abnormality and average hippocampal cell loss in both pathologic groups. CONCLUSIONS: Ipsilateral FLAIR signal abnormalities occur in the majority of patients with isolated HS but are less frequent in those with dual pathology. The presence of increased FLAIR signal is correlated with higher hippocampal cell loss.

Seizure outcome after functional hemispherectomy for malformations of cortical development.

MRI features were correlated with postsurgical seizure outcome in patients with hemispheric malformations of cortical development (MCD). After functional hemispherectomy, 5 of 6 patients (83%) with hemimegalencephaly had persistent, although markedly improved, seizures; 5 of 6 patients (83%) with relative preservation of part of one lobe or atrophy were seizure free. Hemimegalencephaly and other types of hemispheric MCD appear to differ in prognosis for freedom from seizures after functional hemispherectomy.

Temporal lobe epilepsy due to hippocampal sclerosis in pediatric candidates for epilepsy surgery.

OBJECTIVE: To characterize the clinical, EEG, MRI, and histopathologic features and explore seizure outcome in pediatric candidates for epilepsy surgery who have temporal lobe epilepsy (TLE) caused by hippocampal sclerosis (HS). METHODS: The authors studied 17 children (4 to 12 years of age) and 17 adolescents (13 to 20 years of age) who had anteromesial temporal resection between 1990 and 1998. RESULTS: All patients had seizures characterized by decreased awareness and responsiveness. Automatisms were typically mild to moderate in children and moderate to marked in adolescents. Among adolescents, interictal spikes were almost exclusively unilateral anterior temporal, as opposed to children in whom anterior temporal spikes were associated with mid/posterior temporal, bilateral temporal, extratemporal, or generalized spikes in 60% of cases. MRI showed hippocampal sclerosis on the side of EEG seizure onset in all patients. Fifty-four percent of children and 56% of adolescents had significant asymmetry of total hippocampal volumes, whereas the remaining patients had only focal atrophy of the hippocampal head or body. Subtle MRI abnormalities of ipsilateral temporal neocortex were seen in all children and 60% of adolescents studied with FLAIR images. On histopathology, there was an unexpectedly high frequency of dual pathology with mild to moderate cortical dysplasia as well as HS, seen in 79% of children and adolescents. Seventy-eight percent of patients were free of seizures at follow-up (mean, 2.6 years). A tendency for lower seizure-free outcome was observed in patients with bilateral temporal interictal sharp waves or bilateral HS on MRI. The presence of dual pathology did not portend poor postsurgical outcome. CONCLUSIONS: TLE caused by HS similar to those in adults were seen in children as young as 4 years of age. Focal hippocampal atrophy seen on MRI often was not reflected in total hippocampal volumetry. Children may have an especially high frequency of dual pathology, with mild to moderate cortical dysplasia as well as HS, and MRI usually, but not always, predicts this finding. Postsurgical seizure outcome is similar to that in adult series.

Surgical treatment of epilepsy.

Approximately 30-40% of patients with focal epilepsy continue to have seizures despite appropriate medical therapy. Surgical treatments should be considered in this important subset of patients. Recent advances in neuroimaging technology have revolutionized the identification and evaluation of surgical candidates. The goal of the presurgical evaluation (video EEG monitoring, neuroimaging, and neuropsychological assessment) is to delineate the epileptogenic zone. Surgery is recommended when this has been adequately identified and the proposed procedure is expected to result in a high likelihood of seizure freedom and a low risk of neurologic and cognitive morbidity.