Multiple auras: clinical significance and pathophysiology.

BACKGROUND: Patients with partial epilepsy may report multiple types of aura during their seizures. The significance of the occurrence of multiple auras in the same patient is not known. METHODS: The clinical and electrophysiologic characteristics of patients with more than one aura type (abdominal, auditory, autonomic, gustatory, olfactory, psychic, somatosensory, and visual auras), evaluated in the Cleveland Clinic epilepsy monitoring unit between 1989 and 2005, were studied. RESULTS: Thirty-one patients experienced multiple aura types during a seizure. Ninety percent of patients with at least two aura types (n = 31) and 100% percent of patients with at least three aura types (n = 12) had seizures arising from the right/nondominant hemisphere. EEG seizures remained restricted in all patients during their auras. nineteen [corrected] patients had epilepsy surgery with seizure freedom in 53%. Subdural EEG recordings in six patients showed either a march of sequential auras, or in one case, several ictal onset zones resulting in separate isolated auras. Ictal SPECT in six patients with right-sided seizures showed a lack of activation in brainstem structures. CONCLUSIONS: Most patients who report multiple aura types have localized epilepsy in the nondominant hemisphere, and are good surgical candidates. A common mechanism for multiple auras may be a spreading but restricted EEG seizure activating sequential symptomatogenic zones, but without the ictal activation of deeper structures or contralateral spread to cause loss of awareness and amnesia for the auras.

Subdural electrode analysis in focal cortical dysplasia: predictors of surgical outcome.

OBJECTIVE: Patients undergoing epilepsy surgery for focal cortical dysplasia (FCD) guided by subdural EEG generally have a poor surgical outcome. Our objective was to identify predictors of postoperative seizure recurrence in this patient cohort. METHODS: We retrospectively reviewed 48 consecutive surgeries guided by subdural electrode recordings between 1990 and 2004 in patients with a pathologic diagnosis of isolated FCD. Using survival analysis, we analyzed results of the noninvasive evaluation, MRI, subdural interictal and ictal EEG patterns, extent of resection, proximity to eloquent cortex, and postoperative EEG. RESULTS: After a median follow-up of 2.7 years, 45% of patients were completely seizure-free. Most seizures recurred in the first 6 months or between years 2 and 3 after surgery. On univariate analysis, seizure recurrence was associated with bilateral EEG abnormalities, multiple semiologic seizure types, and incomplete resection of the ictal onset zone. The absence of an MRI lesion did not affect outcome, nor did proximity to eloquent cortex. Interictal paroxysmal fast and runs of repetitive spikes correlated with the ictal onset zone, whereas isolated spikes did not. The 6-month EEG predicted ultimate surgical failure in patients seizure-free at that stage. An ictal spread pattern from the edge of the subdural grids was an independent predictor of seizure recurrence on multivariate analysis. CONCLUSIONS: We have identified specific predictive factors that may guide the surgical evaluation of patients with focal cortical dysplasia and intractable epilepsy requiring subdural EEG monitoring. Successful surgical results can be obtained utilizing subdural EEG in carefully selected patients.

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.

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.

Complex partial seizures of frontal lobe onset statistical analysis of ictal semiology.

OBJECTIVE: To identify the ictal semiology of complex partial seizures originating from the frontal lobe (FLCPS) and mesial temporal lobe (MTLE) in patients who became seizure free after surgery. METHODS: We analysed 149 seizures from 42 patients, 28 with MTLE (75 seizures) and 14 with FLCPS (74 seizures) seizure free for at least 1 year after surgery. Fifty-eight symptoms and signs were looked for in every seizure and their time of onset and ending noted. Statistical analysis was then used to define the frequency, time of onset and cluster analysis of these symptoms/signs. RESULTS: Epigastric aura was more frequent in MTLE while an aura of a general body sensation or indescribable feeling occurred only in FLCPS. Alimentary automatisms were more common and occurred earlier in MTLE (P<0.001). Perseverative automatisms, retching and vomiting occurred exclusively in MTLE while bicycling movements occurred only in FLCPS. Abdominal, psychic or olfactory aura followed by behavioural arrest, alimentary automatisms, repetitive distal upper extremity movements, complete loss of consciousness, looking around and whole body movements were typical of MTLE. Repetitive coarse upper extremity movements, complete loss of consciousness, complex motor and hypermotor activity were typical of FLCPS. CONCLUSION: The earliest symptoms and signs as well as their order of appearance allow one to distinguish between complex partial seizures arising from the frontal lobe and mesial temporal lobe.

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.

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.

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.

Symptomatic or cryptogenic partial epilepsy of childhood onset: fourteen-year follow-up.

This study reports on the seizure and psychosocial outcome of 29 patients with electroclinically well-defined childhood-onset symptomatogenic or cryptogenic partial epilepsy with complex partial seizures who were followed prospectively over 14 years. Many were refractory at the time of enrollment. At 14-year follow-up, we acquired information on seizure type and frequency, psychiatric history, substance abuse, criminal activity, in addition to educational, vocational, and marital status through chart reviews and/or structured telephone interviews. Sixteen patients were only treated medically. They were divided by their following responses to medications: eight patients with less than one seizure per month were in the medically responsive group and eight patients with at least one seizure per month constituted the medically refractory group. Thirteen patients underwent focal resection for medically refractory epilepsy. Medically refractory patients displayed worse educational, vocational, social, and behavioral outcomes than medically responsive patients. Behavioral abnormalities persisted or evolved in five medically refractory patients when they became seizure free. Other studies have indicated that patients with medically refractory complex partial seizures have poor psychosocial outcomes. Although behavioral problems can occur even when seizures are well controlled, their early detection and treatment may be essential to the improvement of psychosocial outcomes.

Benign myoclonus of early infancy: an imitator of West's syndrome.

Benign myoclonus of early infancy is a rare condition characterized by nonepileptic spasms that may resemble the epileptic spasms seen in West's syndrome. The spells in benign myoclonus of early infancy begin before age 1 year and are self-limited. The electroencephalogram (EEG) is invariably normal, and neurologic development is not affected. West's syndrome is characterized by infantile spasms that appear before 1 year of age, an abnormal EEG with hypsarrhythmia, and a poor prognosis. We describe six infants who presented for evaluation of clusters of head, trunk or extremity spasms, eye blinking, brief jerking of upper extremities or trunk, and head nodding episodes. In most, a presumptive diagnosis of West's syndrome was made prior to the referral. One infant had been placed on valproate. Routine EEG recordings or prolonged video EEG monitoring were normal both during and between episodes. After the negative evaluations, the diagnosis of benign myoclonus of early infancy was made in each infant. Subsequently, no infant was treated with anticonvulsants. Follow-up revealed complete resolution of the episodes in all children within 2 weeks to 8 months of onset. All had normal neurologic development. Based on our cases and review of the literature, the prognosis for this disorder is excellent. Care should be taken to recognize this rare entity and avoid unnecessary and potentially harmful antiepileptic therapy.

Mental retardation in pediatric candidates for epilepsy surgery: the role of early seizure onset.

PURPOSE: We sought to determine whether early age at seizure onset is a risk factor for mental retardation, independent of etiology. Assessment of risk for mental retardation with continued uncontrolled seizures plays a role in considerations of timing for epilepsy surgery. Previous studies have indicated that onset of seizures in the first years of life may be a risk factor for mental retardation, but the etiologies of the epilepsies were not included in the analyses. METHODS: Intellectual function was assessed at ages 2-20 years during presurgical evaluation in 100 patients with intractable epilepsy due to focal lesions limited to part of one lobe of the brain. Mental retardation (MR) was defined as Full-Scale Intelligence Quotient (FSIQ) < or =70. The age at seizure onset and the seizure frequency were obtained retrospectively. RESULTS: Younger ages at seizure onset were associated with lower FSIQ scores, and mean FSIQ was also significantly lower for patients with onset of epilepsy at < or =24 months of age (74.0 +/- 21.5) versus that in patients with onset of epilepsy later in life (87.8 +/- 18.8; p = 0.005). The frequency of patients with MR was significantly higher for patients with seizure onset at < or =24 months of age (15 of 33, 46%) than for patients with seizure onset later in life (eight of 67, 12%; p < 0.001). This difference persisted within etiologic subgroups. For patients with focal malformation of cortical development, MR was seen in eight (50%) of 16 patients with seizure onset at < or =24 months versus two (10%) of 20 patients with seizure onset at >24 months (p < 0.001); for patients with tumor, MR was seen in four (50%) of eight patients with seizure onset at < or =24 months versus four (13%) of 30 patients with seizure onset at >24 months (p = 0.003); and for patients with hippocampal sclerosis, MR was seen in two (28%) of seven patients with seizure onset at < or =24 months versus none of 30 patients with seizure onset at >24 months (NS). Within the subgroup with daily seizures, MR was present in 13 (65%) of 20 patients with seizure onset at < or =24 months versus five (17%) of 29 patients with seizure onset later in life (p = 0.001). CONCLUSIONS: These results indicate that onset of intractable epilepsy within the first 24 months of life is a significant risk factor for MR, especially if seizures occur daily. The risk based on early age at seizure onset appeared independent of etiology and persisted within subgroups of patients with focal malformation of cortical development, tumor, or hippocampal sclerosis. Prospective studies will be important to clarify whether early surgical intervention may reduce the risk for subsequent MR in carefully selected infants.

Vagus nerve stimulation for children and adolescents with intractable epilepsies.

BACKGROUND: Vagus nerve stimulation (VNS) has been shown to be efficacious in the treatment of patients > 12 years of age with refractory partial epilepsies and it is suggested that VNS should be considered as one of the treatment options for these patients. METHODS: Four patients had partial epilepsies and one had symptomatic generalized epilepsy. After observation of the baseline seizure frequency and the average seizure frequency for 3 months, the VNS system was implanted. Thereafter, seizure frequency, average seizure frequency of each seizure type during the month just before the evaluation, seizure severity, side effects and quality of life were recorded. RESULTS: In four of five patients, overall seizure frequency was reduced > 50% after VNS treatment. The seizure types that showed a > 50% reduction in frequency were auras, focal clonic, generalized tonic clonic seizures, astatic, versive, hypomotor, generalized tonic and generalized clonic seizures according to Lüders' classification. In two patients, as major convulsive seizures were reduced in number after VNS treatment, dialeptic seizures (non-convulsive seizure with lapse of consciousness) gradually appeared. In one patient without significant seizure reduction, quick recovery from postictal periods after generalized tonic seizure was seen after treatment. In one patient with generalized epilepsy, improvement of cognitive function was reported by his guardians. After VNS, the number of antiepileptic drugs was reduced from three to one in one patient. No significant adverse effects were noted in any patients. CONCLUSIONS: Our results suggest that VNS is well tolerated in young patients with intractable epilepsies and it may be an important non-pharmacologic treatment option for children with severe epilepsies who cannot tolerate medical therapy and/or are not candidates for epilepsy surgery.

The relationship between sleep and epilepsy.

Seizures occur extensively during sleep or on awakening in a substantial proportion of patients with epilepsy. Interictal epileptiform discharges are also influenced by sleep and sleep deprivation. Continuous spike-waves in slow-wave sleep are the hallmark of Landau-Kleffner syndrome and ESES (Electrical Status in Slow Sleep). Sleep deprivation is known to influence not only the occurrence but also the symptomatology of epileptic seizures. Sleep architecture and daytime alertness are influenced by seizures and antiepileptic medications. This review examines the clinical and basic science aspects of this relationship between sleep and epilepsy.