Polysomnographic Sleep Patterns in Children and Adolescents in Unresponsive Wakefulness Syndrome.

OBJECTIVES: We aimed (i) to search for qualitative sleep patterns for pediatric unresponsive wakefulness syndrome (SPPUWS) in prolonged polysomnographic (PSG) recordings in children and adolescents with subacute severe disorders of consciousness due to an acquired brain damage; (ii) to investigate the clinical relevance of SPPUWS and of possible neurophysiological markers (rapid eye movement sleep and sleep spindles) in PSG recordings of pediatric patients with unresponsive wakefulness syndrome (UWS). METHODS: We performed a PSG study in 27 children with UWS due to acquired brain damage in the subacute phase. Patients received a full neurological examination and a clinical assessment with standardized scales. In addition, outcome was assessed after 36 months. RESULTS: We identified 6 PSG patterns (SPPUWS) corresponding to increasing neuroelectrical complexity. The presence of an organized sleep pattern, as well as rapid eye movement sleep and sleep spindles, in the subacute stage appeared highly predictive of a more favorable outcome. Correlation was found between SPPUWS and recovery, as assessed by several clinical and rehabilitation scales. CONCLUSIONS: Polysomnography can be used as a prognostic tool, as it can help determine the capability to recover from a pediatric UWS and predict outcome well before the confirmation provided by suitable clinical scales.

Paroxysmal phenomena in severe disabled children with refractory seizures. From clinical to long-video-EEG processing data to re-examine suspect events.

To provide an estimate of the occurrence of misdiagnosis in paroxysmal events in institutionalized children with severe disabilities and refractory epilepsy. A multi-step diagnostic survey, from observational to long-term video-EEG monitoring was performed in 46 severe disabled children. Multirater Kappa statistic was used to assess agreement between investigators and to individualize children who remained with dubious events. Subsequently, prolonged EEG-video monitoring analysis was performed in selected children to define phenomena due to seizures. A total of 128 video records were performed, 64 routine video-EEG and 27 long-monitoring video-EEG data were screened for detailed analysis. Thirty (21 female, 9 male) children (65%) with dubious seizures were identified by video records (concordance K=0.63). Of these, in 18 children (39%) seizures were excluded by routine video-EEG monitoring (K=0.86). Twelve children (26%) required accurate investigations with long-term video-EEG. In 5 children (11%), 3 symptomatic and 2 cryptogenic, very short and subtle seizures were confirmed by investigators concordance (K=0.83). Distinguishing paroxysmal phenomena is a challenge in children with severe disabilities; its most remarkable consequence is inappropriate pharmacological treatment and social costs. Our data suggest that the frequency of misdiagnosis could have been underestimated. The clinicians who manage children with severe disabilities and refractory epilepsy must remain alert to risk of an incorrect treatment.

Variable electrobehavioral patterns during focal nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid.

OBJECTIVE: Nonconvulsive status epilepticus (ncSE) is a severe condition that may result in neurologic sequelae and epilepsy resistant to pharmacologic treatment. We analyze here seizure and electroencephalography (EEG) patterns and their correlation to the development of a chronic epileptic condition in a guinea pig model of focal ncSE induced by intrahippocampal injection of kainic acid (KA). METHODS: Electrobehavioral patterns during ncSE induced by unilateral injection of 1 µg of KA in the CA1 region of the hippocampus were characterized by continuous video-EEG monitoring in 13 guinea pigs bilaterally implanted with recording electrodes in the hippocampus and neocortex. RESULTS: Video-EEG analysis demonstrates a high variability of seizure type and duration during KA-induced ncSE. Seizures showed focal signs correlated with diverse epileptiform EEG discharge distributions, either diffuse or localized. Nonfocal (bilateral motor) signs during seizures most likely correlated with a diffuse EEG pattern. The evolution into a chronic epileptic condition correlated neither with the severity of seizure pattern nor with the diffusion of the EEG discharges observed during the ncSE. SIGNIFICANCE: Video-EEG monitoring in a guinea pig model of ncSE induced by unilateral hippocampal injection of KA demonstrates a high variability of electrobehavioral patterns. We demonstrate that the seizure severity score during focal ncSE is not a predictor of the evolution into a chronic epileptic condition of mesial temporal lobe epilepsy.

A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid.

PURPOSE: Models of temporal lobe epilepsy are commonly utilized to study focal epileptogenesis and ictogenesis. The criteria that define animal models representative of human mesial temporal lobe may vary in different laboratories. We describe herein a focal epilepsy model of mesial temporal (hippocampal) origin that relies on the analysis of interictal and ictal electroencephalography (EEG) patterns and on their correlation with seizure symptoms and neuropathologic findings. The study is based on guinea pigs, a species seldom utilized to develop chronic epilepsy models. METHODS: Young adult guinea pigs were bilaterally implanted under isoflurane anesthesia with epidural electrodes over somatosensory cortex and depth electrodes in CA1 hippocampal region. A stainless steel guide cannula was positioned unilaterally in the right dorsal hippocampus to inject 1 µl of 0.9% NaCl solution containing 1 µg kainic acid (KA). One week after surgery, continuous 24 h/day video-EEG monitoring was performed 48 h before and every other week after KA injection, for no <1 month. EEG data were recorded wide-band at 2 kHz. After video-EEG monitoring, brains were analyzed for thionine and Timm staining and glial fibrillary acid protein (GFAP) immunostaining. KEY FINDINGS: Unilateral injection of KA in dorsal hippocampus of guinea pigs induces an acute nonconvulsive status epilepticus (SE) that terminates within 24 h (n = 22). Chronic seizures with very mild motor signs (undetectable without EEG monitoring) and highly variable recurrence patterns appear in 45.5% (10 of 22) KA-treated animals, with variable delays from the initial SE. In these animals interictal events, CA1 cell loss, gliosis, and altered Timm staining pattern were observed. The induction of a chronic condition did not correlate with the duration of the nonconvulsive acute SE, but correlated with the extension and quality of neuropathologic damage. SIGNIFICANCE: We demonstrate that a model of hippocampal (mesial temporal lobe) epilepsy can be developed in the guinea pig by intrahippocampal injection of KA. Seizure events in this model show little behavioral signs and may be overlooked without extensive video-EEG monitoring. The establishment of a chronic epileptic condition correlates with the extension of the hippocampal damage (mainly cell loss and gliosis) and not with the intensity of the initial SE.

Levetiracetam in submaximal subcutaneous pentylentetrazol-induced seizures in rats.

Despite anticonvulsant efficacy in animal models of generalized epilepsy, levetiracetam was not effective in the maximal subcutaneous PTZ model in mice and rats. Aim of this study was to assess the efficacy of levetiracetam (LEV) against submaximal, s.c. MET test (PTZ at the dose of 70 mg/kg) acute seizures in Wistar rats, in comparison to valproic acid (VPA). Thirty male Wistar rats (P42) were divided in three drug-treatment groups (10 rats in each group) as follows: valproic acid, levetiracetam, and controls. All animals were tested for seizure threshold at age P50. VPA (110 mg/kg) and LEV (108 mg/kg) were freshly dissolved in saline and injected i.p. in 2-3 ml/kg, 15 and 30 min, respectively, before pentylenetetrazol (PTZ) injection at the dose of 70 mg/kg. The average latency of the seizure type 3 (generalized clonic seizure with loss of righting reflexes) significantly differed between controls and the drug-treated animal groups (p < or = 0.02). The average duration of the seizure type 2 (threshold seizure) was significantly longer in both groups compared to controls (<0.02). In conclusion, LEV plays a role against seizures triggered by subcutaneous PTZ injection given at submaximal doses in rats, as demonstrated by a significant increase in duration of the seizure type 2 (threshold seizure).