A follow-up study in children with status epilepticus during sleep: From clinical spectrum to outcome.

PURPOSE: To evaluate the correlation between clinical spectrum and therapeutic outcomes and neuropsychological deficits in children with status epilepticus during sleep (SES). METHODS: The clinical spectrum of patients with SES was defined as follows: status epilepticus of benign childhood epilepsy with centro-temporal spikes (SEBECTs), atypical benign focal epilepsy during childhood (ABFEC), non-idiopathic focal epilepsy (NIFE), and Landau-Kleffner syndrome (LKS). SES cases were divided into 4 groups according to neuropsychological findings before treatment: developmental delay/intellectual disability (DD/ID), cognitive impairment (CI), attention deficit and/or hyperactivity behaviors (AHD), and normal group (NG). The therapeutic outcomes were classified into 3 groups: satisfactory response, recurrence, and seizure control. RESULTS: A total of 39 cases (24 males and 15 females) were recruited, including 3 cases with SEBECTs, 26 with ABFEC, 8 with NIFE [2 with focal cortical dysplasia (FCD)], and 2 with LKS. There were 7 patients in the DD/ID group, 8 in the CI group, 19 in the AHD group, and 5 in the NG group. Neuropsychological outcomes were significantly different among clinical spectrum (P < 0.001), and neuropsychological deficits frequently occurred in the ABFEC group or in the NIFE group. Besides, 18 patients in the satisfactory group had satisfactory response to medicine or surgery (2 out of 18 cases with FCD), whereas recurrence was observed at least one session within one year in 16 cases in the recurrence group, and no improvement in spike-wave index and cognition/behavior was noted in 5 patients in the seizure control group, although seizure could be controlled. There were significant differences in therapeutic outcomes among clinical spectrum (P = 0.041), with the worst outcomes in the NIFE group (only 1 out of 8 with satisfactory good response). CONCLUSIONS: It is important to categorize patients with SES into epilepsy syndromes, including SEBECTs, ABFPEC, NIFE, and LKS; the clinical spectrum may be a significant determinant to influence the outcomes of SES, including neuropsychological deficits and therapeutic outcomes.

The Possible Role of Hypothalamus-Pituitary-Adrenal Dysfunction in Epileptic Spasms.

PURPOSE: To analyze diurnal cortisol (COR) rhythms among children with epileptic spasms (ESs) and explore the relationship between endocrine factors, circadian rhythm, and ES. METHODS: This study assessed the COR and adrenocorticotropic hormone (ACTH) levels at 08:00 and 16:00, and COR values at 00:00 among children with ESs. Additionally, the etiology of ESs was analyzed. All cases were divided into the following three etiology groups: genetic group, structural etiology group, and unknown etiology group. ACTH was administered to 24 patients, who were divided into the positive electroclinical outcome group and negative electroclinical outcome group. All data were analyzed using a two-way repeated measures analysis of variance. RESULTS: All children showed a COR rhythm. Controls displayed a significantly different COR rhythm from that in the ES group (Fgroup*COR =24.100, p = 0.000). It was observed that the ACTH levels at 08:00 (t = -3.720) and 16:00 (t=-3.794) and COR levels at 16:00 (t = -2.264) and 00:00 (t = -4.607) in the ES group were significantly higher than those in the control group (p < 0.05); COR levels at 08:00 were significantly lower among individuals in the structural etiology group (F = 3.828, p < 0.05). COR levels at 08:00 in the negative electroclinical outcome group (668.30 ± 227.42) nmol/L were higher than those in the positive electroclinical outcome group (462.25 ± 249.71) nmol/L. CONCLUSION: Our results suggest that the change in COR rhythm is an important pathophysiological characteristic of ESs, suggesting that hypothalamus-pituitary-adrenal axis dysfunction possibly leads to the different manifestations of ESs.

Acquired epileptiform opercular syndrome evaluated with real-time transcranial Doppler ultrasound-video-electroencephalogram before and after treatment: a case report.

BACKGROUND: Acquired epileptiform opercular syndrome (AEOS) with electrical status epilepticus during sleep (ESES) may be recurrent and intractable. The real-time transcranial Doppler ultrasound-sleep-deprived video electroencephalogram (TCD-SDvEEG) can be used to observe the relationships among hemodynamic, electrophysiological, and clinical factors in a patient during therapy. This study reported the case of a healthy 5-year-old boy with AEOS. CASE PRESENTATION: The patient had initial seizures during sleep at the age of 1 year, with the left mouth pouting, left eye blinking and drooling for several seconds, and, sometimes, the left upper-limb flexion and head version to the left, lasting for 1-2 min. The combined antiepileptic drug regimens, including valproate, lamotrigine, and clonazepam, failed in the present case. Therefore, the add-on high-dose methylprednisolone therapy was provided. Also, the serial TCD-SDvEEG was used to monitor the dynamic changes before and after add-on steroid treatment. The results showed less than 15% variation in the range of blood flow fluctuation with spikes during non-rapid eye movement sleep after treatment. This was similar to the outcomes in healthy children and also accorded with the clinical improvements such as seizure control, drooling control, and language ability melioration. However, 95% of spike-wave index (SWI) was still maintained. The improvements in cerebral hemodynamics and clinical manifestations were faster and earlier than the SWI progression. CONCLUSIONS: The real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.

A missense mutation in SLC6A1 associated with Lennox-Gastaut syndrome impairs GABA transporter 1 protein trafficking and function.

BACKGROUND: Mutations in SLC6A1 have been associated mainly with myoclonic atonic epilepsy (MAE) and intellectual disability. We identified a novel missense mutation in a patient with Lennox-Gastaut syndrome (LGS) characterized by severe seizures and developmental delay. METHODS: Exome Sequencing was performed in an epilepsy patient cohort. The impact of the mutation was evaluated by 3H γ-aminobutyric acid (GABA) uptake, structural modeling, live cell microscopy, cell surface biotinylation and a high-throughput assay flow cytometry in both neurons and non neuronal cells. RESULTS: We discovered a heterozygous missense mutation (c700G to A [pG234S) in the SLC6A1 encoding GABA transporter 1 (GAT-1). Structural modeling suggests the mutation destabilizes the global protein conformation. With transient expression of enhanced yellow fluorescence protein (YFP) tagged rat GAT-1 cDNAs, we demonstrated that the mutant GAT-1(G234S) transporter had reduced total protein expression in both rat cortical neurons and HEK 293 T cells. With a high-throughput flow cytometry assay and live cell surface biotinylation, we demonstrated that the mutant GAT-1(G234S) had reduced cell surface expression. 3H radioactive labeling GABA uptake assay in HeLa cells indicated a reduced function of the mutant GAT-1(G234S). CONCLUSIONS: This mutation caused instability of the mutant transporter protein, which resulted in reduced cell surface and total protein levels. The mutation also caused reduced GABA uptake in addition to reduced protein expression, leading to reduced GABA clearance, and altered GABAergic signaling in the brain. The impaired trafficking and reduced GABA uptake function may explain the epilepsy phenotype in the patient.

Reversible splenial lesion syndrome in children: Retrospective study and summary of case series.

OBJECTIVE: To describe clinical features of reversible splenial lesion syndrome (RESLES) in children. METHODS: Retrospectively analyzed clinical features of RESLES in children and compared differences between severe and non-severe group, classified by clinical global impression-scale; summarized clinical features of children with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from case series. RESULTS: 16 episodes of RESLES occurring in 15 Chinese children were analyzed, with 13 episodes having MERS and 3 episodes with epilepsy. 10 episodes were associated with various pathogens including rotavirus (n=5), adenovirus (n=1), influenza A (n=1), mycoplasma (n=2), and jejunum campylobacter (n=1). The common neurological symptoms included seizure, behavioral changes, altered consciousness and motor deterioration. The lesions of splenium of corpus callosum (SCC), extra-SCC (n=2) or extra-CC (n=1) showed T2-weight and FLAIR hyper-intensity, with the corresponding reduced diffusion. All had complete resolution of radiological changes except 1 episode with small residual. 8 episodes had EEG abnormalities, while elevated white blood count, increased hs-CRP, and hyponatremia were commonly revealed. 7 episodes were given steroid plus therapy, while 3 episodes were treated with antiepileptic drugs. Compared with non-severe group, the number of patients with altered consciousness, EEG abnormalities, motor deterioration, or extra-SCC lesions in severe group was significantly increased. The patients in severe group tended to need longer hospital stay interval. No case caused neurological sequelae, except 1 patient in severe group with recurrent episode and extra-CC lesions having intellectual disability (ID). Five pediatric MERS case series were summarized, including 67 episodes (40 male and 27 female; age ranging 10 m∼13y) from 65 patients, with 33 episodes in Japan, 27 in China, and 7 in Caucasian Australian children, and all patients have a good prognosis except 1 patient with ID (current study). CONCLUSION: Although RESLES in children tend to be a good outcome, the prognosis of patient in severe group, especially with extra-CC lesions, might have neurological sequelae.

[Evolution and prognosis of the acute flaccid paralysis associated with enterovirus 71 infection evaluated through a clinical and magnetic resonance imaging follow-up study].

OBJECTIVE: To explore the development and prognosis of the acute flaccid paralysis (AFP) associated with enterovirus 71 (EV71) infection through clinical follow-up study for clinical and magnetic resonance imaging (MRI) features based on the research progress of virology and pathology. METHOD: Sixteen children with HFMD associated with AFP in hospital from May 1, 2011 to August 31, 2011 were investigated and the patients received intensive rehabilitation training. The 16 cases were divided into two groups (the recovery or the sequela) by if the muscle strength recovered to level 4 after intensive rehabilitation. The MRI findings of 15 children were analyzed and among them, 6 patients were reexamined after one month. The clinical markers were compared between groups including course of disease, WBC, WBC in cerebrospinal fluid (CSF), ventilator support, therapy, the worst muscle strength, the initial tendon reflex, the muscle atrophy, and multi-limb paralysis. The data were analyzed by t test and χ2 test with SPSS10.0. RESULT: All the 16 children were infected with enterovirus 71 (EV71). The myodynamia of 7 children were level 0, 4 children had serious upper limbs paralysis. The neck muscle in 3 cases and the brain stem motor ruckus in 4 cases were involved. The ankle clonus of non-completely paralyzed limbs in 14 cases occurred during rehabilitation. Eight children had the better prognosis, the other 8 children had sequela. 0 level muscle strength (0 case vs. 7 cases, χ2=12.4), the initial tendon reflex (2 cases vs. 8 cases, χ2=9.6), obvious muscle atrophy (0 case vs. 8 cases, χ2=16), were significantly different in the children with the recovery when compared to the sequela (P<0.01). The severe upper limbs paralysis had the worse prognosis than the severe lower limbs paralysis. MR imaging showed signs of spinal nerve root inflammation and the bilateral hyperintense lesions, symmetrical in the posterior portions of the medulla, pons, and asymmetrical in the ventral horns of cervical spinal cord. Signal enhancement occurred only in the early MRI examination. CONCLUSION: In the evolution of AFP due to EV71 infection, the upper motor neuron damage is common, the prognosis is related with the severity of early paralysis and neuron damage. MR imaging is helpful to understand the pathological mechanism of AFP.