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.

Presurgical evaluation of temporal lobe epilepsy using interictal temporal spikes and positron emission tomography.

OBJECTIVE: Our goal was to determine the role of fludeoxyglucose F 18-positron emission tomography (18FDG-PET) and interictal temporal spikes in lateralizing the epileptogenic region in patients who (1) were diagnosed as having temporal lobe epilepsy based on clinical symptoms and exclusively temporal interictal spikes and (2) did not have a structural lesion on magnetic resonance imaging. DESIGN: This was a retrospective study of 40 consecutive patients fulfilling the above criteria who underwent 18FDG-PET scanning. A firm electrophysiologic diagnosis and 1 complete year of postsurgical follow-up, where applicable, were required. Outcome measures included surgical outcome and final electrophysiologic diagnosis. RESULTS: Unilateral, interictal temporal spikes (ITS) were present in 33 (82.5%) of 40 patients. Seven patients (17.5%) had bitemporal, independent spikes. Thirty-one (77.5%) of 40 patients had unilateral temporal hypometabolism (TH). Twenty-eight (70%) patients had concordant TH and ITS. One year after surgery, 31 of 33 patients with unilateral ITS were greatly improved; two of five who had bitemporal ITS showed similar improvement. In 28 patients, unilateral TH and unilateral ITS were concordant. The paired result always concurred with the final neurophysiologic assessment. Surgical outcome between patients with 18FDG-PET showing unilateral TH (26 of 30 greatly improved) and those not showing unilateral TH (six of eight greatly improved) was not significantly different. CONCLUSION: In temporal lobe epilepsy not associated with a mass lesion, unilateral ITS are reliable lateralizing features and suggest a good surgical outcome. Use of 18FDG-PET provides corroborative lateralizing information but 18FDG-PET that fails to show unilateral TH does not preclude a good surgical outcome.

Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults.

BACKGROUND: There is controversy regarding the precise mechanism by which epilepsy results after traumatic brain injury (TBI). Previous reports have suggested that mesial temporal lobe epilepsy may result from TBI only in young children, while neocortical epilepsy arises from TBI in later life. These conclusions were based on surgical series and may be biased because of patient selection. OBJECTIVE: To determine the frequency of mesial temporal lobe as opposed to neocortical epilepsy in patients with intractable epilepsy resulting from TBI after the age of 10 years. PATIENTS AND METHODS: We identified 23 patients with intractable epilepsy who had TBI after the age of 10 years, preceding the onset of epilepsy. Patients were studied by simultaneous videotape and scalp electroencephalographic recording of typical seizures; magnetic resonance imaging; neuropsychologic studies; and, when appropriate, intracarotid amobarbital testing. Two patients underwent anterior temporal lobectomies. RESULTS: Of the 23 patients, 8 (35%) had mesial temporal lobe epilepsy, based on the finding of hippocampal sclerosis on a magnetic resonance imaging scan, consistent interictal and ictal electroencephalographic recordings, evidence of temporal lobe dysfunction on neuropsychologic testing, and characteristic seizure semiology. Two of these patients underwent anterior temporal lobectomies with clinical benefit, and hippocampal sclerosis was confirmed pathologically. In 2 cases, patients were not treated surgically because of bilateral temporal lobe dysfunction noted on intracarotid amobarbital testing. Eleven patients had neocortical epilepsy; 1 had primary generalized epilepsy; and, in 3, the site of seizure onset was not localized. CONCLUSIONS: Mesial temporal lobe epilepsy can result from TBI in adolescents and adults as well as in children, and can often be bilateral and associated with multifocal injury. This information may be useful in developing prophylactic therapy for posttraumatic epilepsy.

Lateralizing signs in intractable partial epilepsy: blinded multiple-observer analysis.

We evaluated the accuracy and interobserver variability of selected ictal and postictal behavioral changes. Three observers, blinded to clinical history, EEG, and side of surgical resection, analyzed videotapes of 166 seizures in 38 patients, looking for lateralizing signs. Twenty-seven patients with temporal lobe resections were seizure-free for > or = 1 year postoperatively, and 11 with extratemporal resections had at least 90% reduction in seizures > or = 1 year postsurgery. The epileptogenic region (ER) was lateralized by analyzing lateralizing signs in 78% of patients; positive predictive value (PPV) was 94% (90% CI = 87% to 100%). Overall kappa was 0.68. Signs were considered present if seen by two or more observers. Forty-five percent had version, ie, forced and sustained head deviation (kappa = 0.76, PPV = 94%); 37% had dystonic posturing of the upper extremity (kappa = 0.47, PPV = 93%); and 34% had unilateral mouth deviation (kappa = 0.83, PPV = 92%). These signs indicated a contralateral ER. Twenty-one percent had unilateral upper extremity automatisms, all ipsilateral to the ER (kappa = 0.65, PPV = 100%); 21% had postictal dysnomia, indicating a dominant-hemisphere ER (kappa = 0.89, PPV = 100%); and 16% had ictal speech, usually indicating a nondominant-hemisphere ER (kappa = 0.75, PPV = 83%). Dystonic posturing, postictal dysnomia, ictal speech, and unilateral upper extremity automatisms may indicate a higher probability of temporal lobe epilepsy. Analysis of lateralizing signs shows good interobserver agreement and provides useful clinical information.

gamma-Aminobutyric acid receptors in normal human brain and Huntington disease.

GABA receptor binding curves were measured in well-washed membrane homogenates from eleven regions of normal human brain and four regions from brains of Huntington disease patients. Computer analysis suggested two populations of receptor sites of different affinity (KD = 10 nM and 240 nM) present in all brain regions but in variable quantity (cerebellar cortex and cerebral cortex greater than basal ganglia greater than deeper brain structures). The number of GABA receptor sites in the caudate-putamen region of Huntington brain was less than normal, but the number of sites was increased in Huntington disease substantia nigra. No differences from normal were found in cerebellar cortex or frontal cortex from Huntington disease, and no significant changes in binding affinity were observed for any of the four regions tested under the conditions used.

Ictal localization of temporal lobe seizures with scalp/sphenoidal recordings.

We assessed the reliability and accuracy of scalp/sphenodial recordings for ictal localization by retrospectively analyzing 706 noninvasive ictal recordings from 110 patients who subsequently underwent stereoencephalographic evaluation. Strictly defined unilateral temporal/sphenoidal ictal patterns correctly predicted findings of depth electrode examination in 82 to 94% of cases. These strictly defined predictive patterns could be detected with excellent interrater reliability. The patterns are misleading in only a minority of cases, but cannot be used in isolation for definite ictal localization.

Supplementary motor area seizures: propagation pathways as studied with invasive recordings.

We studied propagation of epileptic discharges in five patients with supplementary motor area (SMA) seizures with subdural grid electrodes implanted over the dorsolateral frontal neocortex and in the interhemispheric fissure. We found that both interictal and ictal epileptic discharges occurred synchronously in the SMA and the primary cortex. The actively involved electrodes were separated by silent electrodes. The time lag between the SMA and the primary motor cortex averaged 25 msec for interictal and 100 msec for ictal discharges. Cortical stimulations of the affected electrodes showed motor effects in corresponding body parts. All patients underwent resections of the EEG onset zone within the SMA while sparing the primary motor cortex and experienced a significant (>90%) reduction of seizure frequency. We conclude that epileptic activity is propagated between the SMA and the primary motor cortex by a somatotopically organized monosynaptic pathway.

MPTP is proconvulsant acutely but has no long-term effect in rodent models of seizure and epilepsy.

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was used to lesion the substantia nigra of rodents to look for changes in various animal models of epilepsy and seizures. MPTP, acutely administered to C57BL/6J mice, could cause seizures at high doses and enhanced maximal electroshock seizures at lower doses. Older mice were more sensitive to MPTP toxicity. MPTP given over 1 week to produce a 75% drop of striatal dopamine had no effect on seizure thresholds to pentylenetetrazol or picrotoxin and did not change the maximal electroshock seizure. Epileptic gerbils given maximally tolerated doses of MPTP had only a slight striatal dopamine reduction (32%) while seizures remained unaltered. The data are consistent with the hypothesis that chronic dysfunction of dopamine containing substantia nigra neurons have no significant influence on seizures in these animal models.

Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a patient with neurosyphilis.

We report a case of Jarisch-Herxheimer reaction in a patient with neurosyphilis, which was complicated by nonconvulsive status epilepticus. The EEG features suggested a focal seizure onset, although the patient's MRI was normal. JHR is common in the treatment of neurosyphilis, but usually produces only transient systemic constitutional symptoms. Neurologic deterioration is rare, but can be dramatic, as in our patient. NCSE should be considered as an explanation for persistent obtundation and transient focal neurologic findings in this setting.

Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology.

OBJECTIVE: Epilepsy is a common neurologic condition with significant personal, societal, medical, and economic burdens. There are considerable gaps in the quality of care delivered. Measuring the quality of care delivered is the first step to its improvement. Performance measures are easily identified and quantitated ways to assess whether specific activities were carried out during a patient encounter. Therefore, epilepsy performance measures were derived through a standardized systematic process and may be the basis for pay-for-performance initiatives and maintenance of certification requirements. METHODS: Epilepsy measures were developed through the American Medical Association-convened Physician Consortium for Performance Improvement (PCPI) independent measure development process, which marked the first time a medical specialty society followed this process. Guidelines, measures, and consensus papers reviewed for the period 1998 to 2008 using the National Guidelines Clearinghouse, the National Quality Measures Clearinghouse, PubMed, MEDLINE, and the Cochrane Library were evaluated using a framework to determine the acceptability of each guideline or other evidence review document for measures development. Recommendation statements based on level of evidence, importance, validity, and gap in care were developed into candidate measures. A panel of experts from representative organizations vetted the measures. A period of public comment was followed by approval from the American Academy of Neurology and the PCPI. RESULTS: Literature search identified 160 relevant recommendation statements from 19 guidelines and 2 consensus papers. Systematic assessment resulted in 20 recommendation statements that were refined to 8 candidate measures by the expert panel. The measures are relevant to seizure type and frequency, etiology or epilepsy syndrome, EEG, neuroimaging, antiepileptic drug side effects, safety issues, referral for refractory epilepsy, and issues for women of childbearing potential. CONCLUSION: There is a reasonable evidence base, and consensus for, deriving performance measures for quality of epilepsy care. It is anticipated that implementation of these performance measures will improve care for patients with epilepsy if adopted by providers.

Pentobarbital and EEG burst suppression in treatment of status epilepticus refractory to benzodiazepines and phenytoin.

Seven patients with complex partial or secondarily generalized tonic-clonic status epilepticus (SE) refractory to benzodiazepines (BZDs) and phenytoin (PHT) were treated with pentobarbital (PTB) coma with an EEG burst suppression (BSP) pattern. PTB administered by continuous intravenous (i.v.) infusion pump at a loading dose of 6-8 mg/kg in 40-60 min was usually sufficient to produce BSP activity and seizure control. PTB was continued 0-24 h at 1-4 mg/kg/h, adjusted to maintain blood pressure (BP) and BSP. Infusion rate was decreased if systolic BP (SBP) was less than 90 mm Hg. Normal saline fluid challenge was occasionally used to elevate BP, but in no case was it necessary to discontinue PTB infusion or use pressors. Other antiepileptic drugs (AEDs) were maintained at therapeutic levels for chronic seizure protection. Seizures were stopped in all cases. Four patients attained premorbid neurologic status, two patients briefly survived in vegetative states with recurring seizures after PTB withdrawal, and one patient died of asystole after receiving PTB for 7 h. Patients who had poor outcomes had prolonged seizures (16 h to 3 weeks) before institution of PTB anesthesia, and all had significant underlying central nervous system (CNS) pathology. PTB-induced BSP appears to be safe and effective for refractory SE if it is started soon after failure of a BZD and PHT. Ultimate prognosis depends on SE etiology.

Mirror focus: function of seizure frequency and influence on outcome after surgery.

The concept of the mirror focus (MF) implies that an actively discharging epileptiform region may induce similar paroxysmal behavior in a homologous site. In a group of patients with complex partial seizures (CPS) we investigated whether occurrence of a MF was influenced by certain clinical factors and whether surgical outcome was influenced by the presence of an MF. Factors studied included age at onset, duration, and total number of seizures. Patients had had CPS for > 3 years and had pathologically proven temporal lobe neoplasms. Seizure frequency was estimated by the history-taking physician. We estimated total seizure number by multiplying frequency by duration. Seven patients had MF, and 15 did not. Mean age at onset of seizures, duration of seizure disorder, and total seizure number did not vary statistically between the two groups of patients. All patients with an MF except 1 were seizure-free at follow-up. Ten of the 15 patients without MF were seizure-free. Three patients who were not seizure-free had had subtotal resection owing to tumor overlap with eloquent cortex. We conclude that an MF is not a contraindication to operation even when the preponderance of interictal spike activity is contralateral to the tumor or when seizures appear to arise from the MF on scalp EEG.

Modulation of GABAA receptor binding in human brain by neuroactive steroids: species and brain regional differences.

Allosteric modulation by neuroactive steroids of radioligand binding sites on the GABAA receptor complex was demonstrated by autoradiography in vitro in several regions of human brain and the effects compared to those in rat brain. Comparing human and rat, two steroids known to be active in enhancing GABA-mediated postsynaptic inhibition, 5 alpha-pregnane-3 alpha,21-diol-20-one (tetrahydro-deoxycorticosterone, THDOC) and alphaxalone (5 alpha-pregnane-3 alpha-hydroxy-11,20-dione), allosterically inhibited [35S]T-BPS binding to the picrotoxin/convulsant site in both species in several regions including the hippocampus. Unlike rat, human brain binding of [3H]flunitrazepam to the benzodiazepine site was not enhanced by alphaxalone (at any concentration), but was unaffected in many regions and inhibited in others. Binding of [3H]muscimol to high and low affinity GABA sites were enhanced by both steroids in all tested regions of rat brain, although to varying degrees. However, several lobes of human cortex showed no modulation of muscimol binding by either steroid, and THDOC, but not alphaxalone, inhibited in some areas. Comparing regions, THDOC at high concentrations (10 microM) enhanced in human frontal lobe and primary sensory and motor cortex, with greater effect in deep layers than superficial. This steroid had no effect in other parts of parietal lobe and inhibited muscimol binding in temporal lobe, primary visual cortex, and other parts of occipital lobe. Concentration-dependence curves for THDOC showed regional variation, e.g., in the hippocampal formation and surrounding neocortex. These regional and species differences are consistent with the existence of multiple GABAA receptor subtypes that differ in pharmacology. This heterogeneity provides both the opportunity and the difficulty of targeting clinically useful medications such as antiepileptic drugs to the appropriate human brain regions, and the species differences in regional subtype expression suggest caution in use of animal models.

Presence of Bereitschaftspotential preceding psychogenic myoclonus: clinical application of jerk-locked back averaging.

The method of jerk-locked back averaging was applied to six patients with clinically diagnosed psychogenic myoclonus. Five patients had a slow negative EEG shift corresponding to Bereitschaftspotential at the central region starting 0.7 to 2.1 seconds before the onset of the myoclonic jerk. One patient had no potential preceding the myoclonic jerk, whereas a small negative potential preceded the voluntary movement mimicking the jerk. The demonstration of Bereitschaftspotential before an apparently involuntary myoclonic jerk helps the clinical diagnosis of psychogenic myoclonus, although the absence of Bereitschaftspotential does not necessarily indicate that the movement is involuntary. Jerk-locked back averaging is clinically useful as a specific laboratory examination in this condition.

Chronic intractable epilepsy as the only symptom of primary brain tumor.

We identified 39 patients with chronic epilepsy (seizures > or = 2 years) proven to have primary brain tumors. These cases represent approximately 12% of the surgery cases for epilepsy in the same period. Mean age of seizure onset was 13.2 years: mean duration before operation was 10.5 years. Thirty-eight of 39 had normal neurologic examination. Twenty-six tumors were temporal, 7 were frontal, 4 were parietal, and 2 were occipital. Nine of 26 (34.6%) of the temporal group had contralateral interictal EEG spikes. Pathology was 15 ganglioglioma, 13 low-grade astroctoma, 4 oligodendroglioma, 2 low-grade mixed glioma, 1 pleomorphic xanthoastrocytoma, 2 dysembryoplastic neuroepithelial tumor, and 1 ependymoma. Postoperative seizure frequency (minimum follow-up 6 months) ranged from 15 to 16 seizure-free auras only in patients with temporal tumors and total gross tumor removal (mean follow-up 28 months) to 0 of 6 seizure-free in patients with extratemporal tumors who underwent subtotal resection or biopsy.