Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics.

Evidence-based guidelines, or recommendations, for the management of infants with seizures are lacking. A Task Force of the Commission of Pediatrics developed a consensus document addressing diagnostic markers, management interventions, and outcome measures for infants with seizures. Levels of evidence to support recommendations and statements were assessed using the American Academy of Neurology Guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The report contains recommendations for different levels of care, noting which would be regarded as standard care, compared to optimal care, or "state of the art" interventions. The incidence of epilepsy in the infantile period is the highest of all age groups (strong evidence), with epileptic spasms the largest single subgroup and, in the first 2 years of life, febrile seizures are the most commonly occurring seizures. Acute intervention at the time of a febrile seizure does not alter the risk for subsequent epilepsy (class 1 evidence). The use of antipyretic agents does not alter the recurrence rate (class 1 evidence), and there is no evidence to support initiation of regular antiepileptic drugs for simple febrile seizures (class 1 evidence). Infants with abnormal movements whose routine electroencephalography (EEG) study is not diagnostic, would benefit from video-EEG analysis, or home video to capture events (expert opinion, level U recommendation). Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with magnetic resonance imaging (MRI) recommended as the standard investigation at tertiary level (level A recommendation). Genetic screening should not be undertaken at primary or secondary level care (expert opinion). Standard care should permit genetic counseling by trained personal at all levels of care (expert opinion). Genetic evaluation for Dravet syndrome, and other infantile-onset epileptic encephalopathies, should be available in tertiary care (weak evidence, level C recommendation). Patients should be referred from primary or secondary to tertiary level care after failure of one antiepileptic drug (standard care) and optimal care equates to referral of all infants after presentation with a seizure (expert opinion, level U evidence). Infants with recurrent seizures warrant urgent assessment for initiation of antiepileptic drugs (expert opinion, level U recommendation). Infantile encephalopathies should have rapid introduction and increment of antiepileptic drug dosage (expert opinion, level U recommendation). There is no high level evidence to support any particular current agents for use in infants with seizures. For focal seizures, levetiracetam is effective (strong evidence); for generalized seizures, weak evidence supports levetiracetam, valproate, lamotrigine, topiramate, and clobazam; for Dravet syndrome, strong evidence supports that stiripentol is effective (in combination with valproate and clobazam), whereas weak evidence supports that topiramate, zonisamide, valproate, bromide, and the ketogenic diet are possibly effective; and for Ohtahara syndrome, there is weak evidence that most antiepileptic drugs are poorly effective. For epileptic spasms, clinical suspicion remains central to the diagnosis and is supported by EEG, which ideally is prolonged (level C recommendation). Adrenocorticotropic hormone (ACTH) is preferred for short-term control of epileptic spasms (level B recommendation), oral steroids are probably effective in short-term control of spasms (level C recommendation), and a shorter interval from the onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome (level C recommendation). The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency (expert opinion, level U recommendation). The identification of patients as potential candidates for epilepsy surgery should be part of standard practice at primary and secondary level care. Tertiary care facilities with experience in epilepsy surgery should undertake the screening for epilepsy surgical candidates (level U recommendation). There is insufficient evidence to conclude if there is benefit from vagus nerve stimulation (level U recommendation). The key recommendations are summarized into an executive summary. The full report is available as Supporting Information. This report provides a comprehensive foundation of an approach to infants with seizures, while identifying where there are inadequate data to support recommended practice, and where further data collection is needed to address these deficits.

Electroencephalographic seizures after neonatal cardiac surgery with high-flow cardiopulmonary bypass.

BACKGROUND: Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, severity, and factors associated with EEG seizures. METHODS: The CPB protocol included 150 mL/kg/min flows, pH stat management, hematocrit >30%, and high-flow antegrade cerebral perfusion. Regional cerebral oxygen saturation (rSo(2)) was monitored, with a treatment protocol for rSo(2) <50%. EEG was assessed for seizures. RESULTS: Sixty-eight patients (36 single ventricle [SV] and 32 2-ventricle [2V]) were monitored for a total of 4824 hours. The total midazolam dose was 2.4 mg/kg (1.5-7.3 mg/kg) (median, 25th-75th percentile) for the SV group and 1.3 mg/kg (1.0-2.7 mg/kg) for the 2V group (P = 0.009). One SV patient experienced 2 brief EEG seizures postoperatively (1.5% incidence; 95% confidence interval: 0.3%-7.9%). The SV patients experienced a significant incidence of cerebral desaturation (rSo(2) <45% for >240 minutes total) perioperatively (18 of 36 SV vs 0 of 32 2V patients, P < 0.001). This difference did not affect electrographic seizure occurrence or other EEG characteristics. CONCLUSIONS: EEG seizures are infrequent in neonates undergoing surgery with high-flow CPB. Cerebral desaturation did not affect EEG seizure occurrence; however, benzodiazepines may play a role in suppressing postoperative seizures caused by cerebral hypoxemia in this patient population. Using this anesthetic and surgical protocol, EEG seizures are a poor surrogate marker for acute neurological injury in this population.

Changes in individual and group spatial and verbal learning characteristics after anterior temporal lobectomy.

PURPOSE: To evaluate the effects of anterior temporal lobectomy (ATL) on individual and group spatial and verbal learning and memory abilities as a function of side of surgery and seizure control outcome. METHODS: We evaluated pre- and postsurgical learning and memory abilities of 75 left-hemisphere language dominant individuals who underwent ATL (33 left, 42 right) using the 8-trial Nonverbal Selective Reminding test and the 12-trial Verbal Selective Reminding test. RESULTS: Reliable change index methods indicated that 40.5% of individuals who underwent right-ATL had a clinically significant decline in spatial memory, and 62.5% of individuals who underwent left-ATL had a significant reduction in verbal memory. Growth curve analyses indicated that both side of surgery and poor seizure outcome independently affected the learning slope in the best fitting models. Left-ATL reduced the slope, but did not affect the overall shape, of verbal learning across trials. On the other hand, poor seizure control outcome affected the slope of spatial learning regardless of the side of surgery. DISCUSSION: Results demonstrate both individual and group declines in spatial memory and learning after ATL. Results suggest that individuals who undergo right-ATL should be counseled regarding the likelihood of a decline in spatial memory and learning abilities after ATL. Results also suggest that individuals with poor seizure control after ATL should be referred for rehabilitation services given the significant declines in spatial and verbal memory that occurred in our sample regardless of side of surgery.

Memory, emotional and vocational impairments before and after anterior temporal lobectomy for complex partial seizures.

PURPOSE: To assess the pre- and postsurgical frequency of memory, emotional, and vocational impairments in patients who underwent anterior temporal lobectomy (ATL), and to assess the relationship between emotional disturbance and memory abilities after ATL. METHODS: Retrospective analysis of data was performed on 90 patients with medically intractable complex partial seizures who underwent ATL between 1981 and 2003. Patients were evaluated an average of 5 months before surgery and 11.3 months after surgery. RESULTS: A moderate to high frequency of memory impairment (44.4%; verbal or nonverbal), emotional disturbance (38.9%) and unemployment (27.8%) existed in the same individuals both before and after surgery. There were small to moderate rates of new onset memory (18.9%), emotional (11.1%), and vocational (7.8%) difficulties after surgery often regardless of seizure control outcome. Patients who underwent left-ATL and had emotional disturbance after surgery had the lowest verbal memory test scores. CONCLUSIONS: Results highlight the importance of taking into account emotional status when assessing memory abilities after ATL. Results replicate the finding of moderate to high frequencies of memory impairment, emotional disturbance, and unemployment both before and after ATL. Results provide support for the rationale that cognitive, psychiatric and vocational interventions are indicated to mitigate the problems that exist before and persist after ATL.

Seizure control and cognitive outcome after temporal lobectomy: a comparison of classic Ammon's horn sclerosis, atypical mesial temporal sclerosis, and tumoral pathologies.

PURPOSE: Neuropathologic examination of resected tissue after anterior temporal lobectomy (ATL) for treatment of complex partial seizures revealed several distinct histologic substrates. Our study examined the relation between neuropathology, seizure control, and cognition in ATL patients and described preliminary profiles to aid in the prediction of outcome. METHODS: Of the 149 patients who underwent ATL from 1980 to 1999, long-term follow-up was available for 145. Specimens from 124 of the 145 patients had histologic findings consistent with one of three diagnoses: classic Ammon's horn sclerosis (cAHS; n = 75), atypical mesial sclerosis (Atypical; n = 21), or low-grade tumor (Tumor; n = 28). The other 20 patients had diverse pathologies that were insufficient for analysis. ATL patients underwent a complete preoperative and 68 underwent a postoperative neuropsychological evaluation. RESULTS: Of the 145 patients, 84% of cAHS, 57% of Tumor, and 29% of Atypical patients had a > or =95% reduction in seizure frequency. Neuropsychological testing suggested that cAHS patients demonstrate more generalized preoperative cognitive impairment than do the Atypical or Tumor patients. The Atypical group recalled significantly less nonverbal material after surgery than did the cAHS or Tumor groups. Stratification by both pathology and surgery side revealed that the right Atypical patients declined more on information processing and set shifting. CONCLUSIONS: Patients with cAHS or Tumor demonstrated better seizure control and fewer declines in cognitive functioning after ATL than did the Atypical patients, highlighting the need to investigate this group as a distinct entity.