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.

Postictal serum creatine kinase in the diagnosis of seizure disorders.

We prospectively correlated daily serum creatine kinase (CK) levels with the occurrence of different types of epileptic and nonepileptic seizures documented by video EEG recording in 22 hospitalized patients. Prolonged postictal CK elevations, 8.0 to 19.2 times baseline, were seen following six (15%) of 41 generalized tonoclonic seizures. No CK elevations were seen following 147 complex partial, focal motor, absence, and tonic seizures or 55 psychogenic seizures, 89% of which involved vigorous muscular activity. Six of 12 patients with generalized tonoclonic seizures had postictal CK elevations compared with none of six patients with psychogenic seizures and none of 15 patients with complex partial, focal motor, absence, and tonic seizures. Thus, postictal CK determination can serve as an adjunctive test for differentiation between psychogenic and epileptic generalized tonoclonic seizures.

Complex partial seizures of childhood onset. A five-year follow-up study.

Few detailed studies have examined the long-term outcome of complex partial seizures (CPS) in children and adolescents. Previous studies have selected patients on clinical criteria only or have included those with benign focal epileptiform discharges of childhood, nonepileptiform sharp transients, and generalized epileptiform discharges. We have followed up 29 patients with clinically and electroencephalographically defined CPS of childhood onset for five years or more. Twelve patients are seizure free, eight of them after having epilepsy surgery. Of the remaining, eight patients have intractable seizures. Only one patient was able to discontinue anticonvulsant therapy after epilepsy surgery. No patient had spontaneous remission of seizures without anticonvulsant medications. School difficulties, behavior problems, and unemployment were seen in half the group. We believe CPS in this age group are difficult to control and need aggressive management. In selected patients, epilepsy surgery offers a good chance of seizure control and improvement of educational, social, and vocational potential.

Comparison of scalp electroencephalogram with subdural electrocorticogram recordings and functional mapping in frontal lobe epilepsy.

We compared the findings of scalp electroencephalogram with subdural electrode array (SEA) recordings in 19 patients with refractory frontal lobe epilepsy. Prolonged scalp interictal recordings localized the epileptogenic zone in 12 patients; seven had no interictal sharp waves. The SEAs showed multifocal interictal sharp waves in all patients. Seven patients with localized seizure onset on scalp recording showed extensive ictal onset on the SEA recording. Five patients with lateralized seizure onset to one hemisphere on scalp recording were found to have ictal onset on SEA restricted to a smaller area. Because of the large epileptogenic zone found on SEA recordings, a complete resection was possible in only five (33%) of the 15 patients who had resections. Eight (53%) of the 15 patients benefited from surgery (mean follow-up, 4.6 years). The SEAs also allowed functional localization in most patients. From these data, we suggest that a localizing scalp electroencephalogram in patients with frontal lobe epilepsy may be misleading because SEA recordings show larger epileptogenic zones than anticipated. Furthermore, we postulate that the larger extensive epileptogenic zone may account for the poorer surgical outcome in patients with frontal lobe epilepsy compared with patients with temporal lobe epilepsy.

Electrophysiologic pathologic correlations in patients with complex partial seizures.

We studied interictal activity and site of ictal onset in 26 patients with complex partial seizures of temporal lobe origin. All patients had prolonged electrocorticographic recordings from subdural electrode arrays placed both over the convexity and beneath the temporal lobe. We found a significant correlation between the epileptogenic focus and the type of pathologic lesion found at time of surgery. Macroscopic lesions strongly tended to have an epileptogenic focus on the lateral surface of the temporal lobe; patients with only microscopic abnormalities tended to have an epileptogenic focus in the mesial/basal region of the temporal lobe.

Ictal amaurosis: MRI, EEG, and clinical features.

We studied seven consecutive patients who experienced amaurosis as a prominent feature of their seizures. The mean age of seizure onset was 4 years. Six patients had MRI abnormalities including ischemic, traumatic, and space-occupying lesions, with five limited to the parietal-occipital region. Six patients had unilateral, posterior interictal spike and slow wave complexes. Four patients experienced severe postictal headache and nausea. Absence of a family history of seizures distinguished the patients with MRI lesions from previously presented series of benign occipital lobe epilepsy. We conclude that the constellation of ictal amaurosis, occipital paroxysms, and postictal migrainous symptoms does not necessarily signify a benign, nonlesional epilepsy; MRI is recommended for such patients without a family history of similar seizures.

Benign childhood epilepsy with centrotemporal spikes: is it always benign?

Most children with benign childhood epilepsy with centrotemporal spikes have few seizures, and some have only one. We describe two children with interictal and ictal findings consistent with this epileptic syndrome but with severe intractable seizures and cognitive decline that resulted in consideration for epilepsy surgery. Spontaneous remission occured in one child; the other is still young. Despite the high seizure burden and cognitive decline, surgical consideration should be withheld, as these seizures are likely to remit.

Worsening seizures after surgery for focal epilepsy due to emergence of primary generalized epilepsy.

Our patient underwent right anteromesial temporal resection at 17 years of age for intractable complex partial seizures due to hippocampal sclerosis, and then developed juvenile myoclonic epilepsy after a change in medication. Postoperative seizures ceased after a change to valproate monotherapy. Our patient reminds us to remain aware that generalized and focal epilepsy may coexist as an unusual cause for surgical failure. We feel that these patients may still be favorable candidates for epileptic surgery, as long as the focal epileptogenic zone is amenable to resection and the generalized epilepsy appears to be readily controllable.

Epilepsy surgery in the setting of periventricular leukomalacia and focal cortical dysplasia.

We report an infant who had successful epilepsy surgery for intractable infantile spasms in the setting of bilateral periventricular leukomalacia and remote germinal matrix hemorrhage. Although MRI gave evidence of a diffuse cerebral insult and EEG showed hypsarrhythmia, focal epileptogenicity was suggested by previous partial seizures with onset over the right temporoparietal-occipital region and PET hypometabolism in that same area. Right temporoparietal and lateral occipital resection at 15 months resulted in seizure freedom and dramatic developmental progress at 1-year follow-up. Histopathologic examination of resected tissue showed cortical dysplasia, possibly due to the same insult that also resulted in the bilateral periventricular leukomalacia. From an etiologic perspective, this is one of very few reported cases strongly implicating acquired focal cortical dysplasia in response to a prenatal insult. From a clinical perspective, the case illustrates that the spectrum of potential surgical candidacy in infants may be broader than usually suspected.

Language dominance in patients with early childhood tumors near left hemisphere language areas.

RATIONALE: Language function often develops in the right hemisphere following an acute left hemispheric insult in early childhood. Little is known, however, about lateralization of language function in patients with early childhood tumors near potential left hemisphere language areas. Issues of language dominance are important in the strategy for resection of left temporal and frontal tumors. METHODS: We studied 12 patients who had determination of hemispheric language dominance by the intracarotid amobarbital procedure prior to resection of a left inferolateral frontal or left mid or posterior temporal tumor that (1) was near a classic language area and (2) first manifested with partial seizures by age 6 years (mean, 3.7). RESULTS: Hemispheric language dominance was left in 10 patients (83%), right in one patient, and bilateral in one patient. Six patients with left temporal tumors had localization of Wernicke's area with cortical stimulation, and in five the language area was posterior to the tumor. In one patient, the tumor infiltrated Wernicke's area. Eleven of the 12 patients had complete tumor resection (mean age at operation, 11.8 years) and were seizure-free at follow-up (mean, 3.1 years). Neuropsychological testing showed a tendency for improved language function after operation, and no patient had new overt language deficits. CONCLUSIONS: Early low-grade left frontal and temporal tumors usually did not result in transfer of language dominance to the contralateral hemisphere. Tumors may grow slowly along with the developing brain in young children, with continued left hemisphere language development in regions separate from the neoplasm. Successful tumor resection can be accomplished, but it may require cortical stimulation for localization and sparing of nearby language areas.

Serum prolactin levels after epileptic seizures.

We prospectively studied serum prolactin (PRL) elevation after different types of documented seizures in 17 patients. Marked PRL elevations above normal and above three times baseline were seen at 15 or 30 minutes after 20 of 25 (80%) generalized tonic-clonic, 13 of 30 (43%) complex partial, and 1 of 10 (10%) simple partial seizures. Although marked postictal PRL elevation is a sensitive indicator of recent epileptic seizures, a normal 15- or 30-minute postictal PRL level does not exclude an epileptic seizure.

The source of 'paradoxical lateralization' of cortical evoked potentials to posterior tibial nerve stimulation.

We report the potentials elicited by posterior tibial nerve stimulation and recorded simultaneously from the scalp and from electrodes within the interhemispheric fissure. The primary cortical potential was recorded from cortex contralateral but from scalp ipsilateral to the stimulated nerve. The scalp recordings thus demonstrated "paradoxical lateralization" as reported previously, and the similar morphology of the scalp and contralateral cortical recordings confirm that this "paradoxical lateralization" is most likely the result of a horizontal dipole located within the interhemispheric fissure.

Versive eye movements elicited by cortical stimulation of the human brain.

We studied the eye movements (EM) elicited by electrical stimulation of the frontal lobe in 19 awake patients evaluated with subdural electrodes for epilepsy surgery. All patients had only contralateral conjugated EM. They were saccadic in 16 patients (84%). Head version, always following the eye deviation, occurred in 11 patients (58%). We also determined the eye field somatotopic distribution analyzing the responses obtained from the electrodes adjacent to the eye fields. All patients had motor cortex contiguous to the eye fields. In 17 patients (90%) the eye fields were located in front or at the level of the motor representation. There was no silent cortex between the motor strip and the eye fields.

Ipsilateral forced head and eye turning at the end of the generalized tonic-clonic phase of versive seizures.

We studied 61 spontaneous seizures in 27 epileptic patients with simultaneous EEG and video recording. Each seizure had an initial forced turning (versive) head and eye movement contralateral to the EEG location of seizure onset. Twelve of the 27 secondarily generalized versive seizures also had ipsilateral head and eye version at the end of the generalized convulsion. Initial contraversion and late ipsiversion both appeared to result from ictal activation of frontal contraversive areas in the hemisphere that, at the time, was predominantly involved in the seizure discharge. During initial contraversion, ictal activation was predominant in the hemisphere of seizure onset; during late ipsiversion, in the hemisphere involved by secondary generalization. Late version, unlike initial version, is frequently ipsilateral and cannot be assumed to indicate seizure onset in the contralateral hemisphere.

The lateralizing significance of versive head and eye movements during epileptic seizures.

We studied 37 patients who had head and eye turning during 74 spontaneous epileptic seizures. Videotapes and EEGs were analyzed independently. Turning movements were classified without knowledge of EEG or clinical data as either versive (unquestionably forced and involuntary, resulting in sustained unnatural positioning) or nonversive (mild, unsustained, wandering, or seemingly voluntary). Videotape observations were then correlated with the EEG location of seizure onset. Contralateral versive head and eye movements occurred during 61 seizures in 27 patients, but ipsilateral versive movements did not occur. Nonversive lateral head and eye movements occurred ipsilaterally and contralaterally with equal frequency and were nonlocalizing, but versive movement was a reliable lateralizing sign.

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.

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.

Supplementary motor seizures: clinical and electroencephalographic findings.

The clinical and EEG features of 11 patients with seizures arising in the supplementary motor area (SMA) were reviewed. All patients underwent prolonged EEG with simultaneous video recording. Three patients had recordings and electrical stimulation of the SMA using subdural electrode arrays. All patients had preservation of consciousness during the seizure unless it became secondarily generalized. Tonic posturing of the extremities was present in all patients, and in seven it was present bilaterally. Adversive movements were not seen unless the seizure became secondarily generalized. Interictal and/or ictal abnormalities were present at or adjacent to the midline in ten patients. Seizures arising from the supplementary motor region are clinically distinct, and the diagnosis can almost always be verified with prolonged EEG/video recording.

Outcome of psychogenic seizures in children and adolescents compared with adults.

We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention.

Seizure symptomatology in infants with localization-related epilepsy.

The clinical characteristics of seizures in adults and children with localization-related epilepsy have been clearly described and classified, but few data are available based on video EEG studies of postneonatal infants under 2 years of age. We analyzed 125 videotaped seizures from 23 infants aged 2 to 24 months with localization-related epilepsy defined by localized ictal EEG or localized lesion on neuroimaging with seizure-free surgical outcome. Seizure symptomatology was classified based on observable behavioral and motor manifestations and then correlated with location of the epileptogenic zone. Seizures characterized by decrease in behavioral motor activity with indeterminate level of consciousness and minimal or no automatisms ("hypomotor" seizures) arose from temporal, temporoparietal, or parieto-occipital regions (7 patients). Seizures with localized or bilateral clonic, tonic, or atonic motor phenomena arose predominantly from frontal, frontocentral, central, or frontoparietal areas (12 patients). One patient had versive seizures arising from the contralateral occipital lobe, 2 patients had infantile spasms (one with a frontal tumor, one with temporo-parieto-occipital dysplasia), and one patient had unclassifiable seizures. Disruption of temporal or temporoparietal function resulted primarily in diminution of behavioral activity, whereas ictal activation of motor areas during frontal or central onset seizures resulted mainly in localized or generalized motor phenomena. Infantile spasms occurred because of lesions in either location. Using an approach based on easily observable behavioral and motor phenomena, it was possible to classify the seizures in all but one infant.