Long-term seizure outcome and risk factors for recurrence after extratemporal epilepsy surgery

Purpose: We aimed to assess long‐term seizure outcome and risk factors for seizure recurrence in a cohort of patients who have undergone extratemporal resection for management of refractory seizures. Methods: Eighty‐one patients underwent extratemporal resection at Austin Health, Melbourne, Australia (1991–2004). Seizure recurrence was any postoperative disabling seizure (complex partial seizure [CPS] ± secondary generalization). Multivariate Cox proportional hazards regression models examined potential preoperative and perioperative risk factors and the risk associated with early postoperative seizures (≤28 days postsurgery). The change between preoperative and postoperative seizure frequency was also measured. Key Findings: Median follow‐up was 10.3 years (range 1–17.7). The probabilities of freedom from disabling seizures (on or off antiepileptic medication) were 40.7% (95% confidence interval [CI] 30–51) at 1 month, 23.5% (95% CI 15–33) at 1 year, and 14.7% (95% CI 8–23) at 5 years postoperative. Reduction of disabling seizures to at least 20% of preoperative frequency was attained by 57% of patients at 5 postoperative years. Of the preoperative/perioperative factors, focal cortical dysplasia (FCD) type 1 (hazard ratio [HR] 1.90, 95% CI 1.08–3.34, p = 0.025) and incomplete resection (HR 1.71, 95% CI 1.06–2.76, p = 0.028) were independent recurrence risks. After surgery, an early postoperative seizure was the only factor associated with higher risk (HR 4.28 [2.42–7.57], p = 0.00). Significance: Distinction between subtypes of focal cortical dysplasia, which can be made using magnetic resonance imaging (MRI) criteria, may be useful for preoperative prognostication. Early seizures after surgery are not benign and may be markers of factors that contribute to seizure recurrence. Most patients achieve substantial reduction in seizure frequency. Further study of the significance of this reduction in terms of surgical “success” or otherwise is required.     

A detailed semiologic analysis of childhood psychogenic nonepileptic seizures

Purpose: Psychogenic nonepileptic seizure (PNES) is an important differential diagnostic problem in patients with or without epilepsy. There are many studies that have analyzed PNES in adults; currently, however, there is no systematic assessment of purely childhood PNES semiology. Our study based on a large pediatric video‐electroencephalography (EEG) monitoring (VEM) cohort, provides a detailed analysis of childhood PNES and assesses the usability of the current classification system described in adults. Methods: Medical and video‐EEG records of 568 consecutive children (younger than 18 years) who underwent video‐EEG monitoring (VEM) at our hospital were reviewed. Aura, type of movement, anatomic distribution, synchrony, symmetry, eye movement, responsiveness, vocalization, hyperventilation, vegetative and emotional signs, presence of eyewitness, and duration of the event were recorded among children with the diagnosis of PNES. We also compared our data with those of earlier adult studies. Key Findings: Seventy‐five archived PNES of 27 children (21 girls; age 8–18 years) were reanalyzed. Nine children (33%) had the diagnosis of epilepsy currently or in the past. Mean age at the time of PNES onset was 11.6 (standard deviation 3.2) years. Mean duration of PNES was longer (269 s) compared to seizures of the epileptic group (83 s; p = 0.002). Eyewitnesses (mostly parents) were present in 89% of cases. Eighty percent of PNES had an abrupt start, with 68% also ending abruptly. In only 15% of events were the patients eyes closed at the beginning of the attack. Patients were unresponsive in 34%. The most frequent motor sign was tremor (25%) with the upper, rather than lower limbs more frequently involved. Pelvic thrusting was seen in only two attacks. Emotional—mostly negative—signs were observed during 32 PNES (43%). Based on Seneviratne et al.’s classification, 18 events (24%) were classified as rhythmic motor PNES, only half the frequency of that previously described in adults. No hypermotor PNES was found. The frequency of complex motor PNES (13%) and mixed PNES (4%) showed similar frequency in children as in adults. Dialeptic PNES was found more frequently among younger children. All PNES belonged to the same semiologic type in 23 patients (85%). Significance: Because homogeneity of PNES within a patient was high in the pediatric population, we found it useful to classify PNES into different semiologic categories. Dialeptic PNES seems to be more frequent among younger children. Tremor is the most frequent motor sign and usually accompanied by preserved responsiveness in childhood. Negative emotion is commonly seen in pediatric PNES, but pelvic thrusting is a rare phenomenon. We, therefore, suggest a modification of the present classification system in which PNES with motor activity is divided into minor and major motor PNES, and the latter group is subdivided into synchron rhythmic motor and asynchron motor PNES. We believe that our study, a detailed analysis on the semiology and classification of purely childhood PNES might assist the early and precise diagnosis of nonepileptic paroxysmal events.     

Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study

Purpose: To evaluate the long‐term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE). Methods: This phase III, open‐label, long‐term, follow‐up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic–clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000–4,000 mg/day; 20–80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention‐to‐treat (ITT) population, N = 217] and subpopulations with tonic–clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline. Key Findings: One hundred twenty‐five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1–Q3) exposure to LEV was 2.1 (1.5–2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or ≥2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of ≥6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of ≥6 months from tonic–clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment‐emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%). Significance: Adjunctive LEV (range 1,000–4,000 mg/day) demonstrated efficacy as a long‐term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated.     

Neurocognitive profiles in children with epilepsy

Purpose: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization‐related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles. Methods: Fifty‐one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within‐group analyses were also conducted to examine seizure‐related factors that may be related to neuropsychological test performance. Key Findings: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another. Significance: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE.     

CLINICAL CASE: VERMIS HYPOPLASIA WITH FEATURES OF SMITH-LEMLI-OPITZ SYNDROME

This article attempts to describe a very unusual case of a boy aged 15, who has had intractable epileptic phenomena, mental retardation, megalocephaly, micrognathy, syndactyly, small tongue, hypoplastic genitalia, gynecomasty, obesity, and slight left body hemiatrophy. Neurologically the patient has had hypotonia of the lower limbs, cerebellar dysfunction including horizontal nystagmus, bilateral intention tremor, dysdiadokokinesia, gait ataxia. The clinical investigation revealed low plasma cholesterol and hypoplasia of the vermis in MRI. The epileptic phenomena were intractable and polymorphous. One should have thought that this is an unusual case of Smith-Lemli-Opitz syndrome associated with features of Joubert syndrome.     

Pediatric Neurocritical Care

Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-011-0093-6) contains supplementary material, which is available to authorized users.     

IL-1β: an important cytokine associated with febrile seizures?

Febrile seizures (FSs) are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β (IL-1β) is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.     

ACS Chemical Neuroscience Molecule Spotlight on Potiga (Ezogabine)

On June 10th, 2011, the U.S. Food and Drug Administration approved Potiga (ezogabine) as an add-on medication for the treatment of seizures in adults, and it is being developed by Valeant Pharmaceuticals.     

Kinetics of Serum Neuron-Specific Enolase and Prolactin in Patients After Single Epileptic Seizures

PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.