Febrile Status Epilepticus Research Articles

Children with new-onset refractory status epilepticus from a multicenter US registry

Introduction: We describe the clinical presentation of new-onset refractory status epilepticus of unknown etiology in children. Methods: We analyzed patients within the pediatric Status Epilepticus Research Group (pSERG) cohort with the following inclusion criteria: 1) age 1–21 years; 2) first episode of RSE requiring more than 2 anti-seizure medications (ASM); 3) RSE episode between 06/2011 and 10/2016. We excluded patients with a history of developmental delay and/or epilepsy. We compare these patients to those with a first refractory status epilepticus (RSE) due to an identified etiology. Results: Fifty four patients were eligible. The median age was 5 years (IQR 1.9, 10.6). The most frequent etiologies were infection (15%), febrile status epilepticus (15%) and acute brain lesions (13%). No etiology was found in 18 patients (33%). In the group with unknown etiology, 15 patients (83%) required intubation and the median duration of ICU stay was 4.8 days (IQR 2, 49). These patients received a median of 3 ASM (IQR 2, 4) and 1 continuous infusion (IQR 0, 3). Compared to patients with an etiology, patients with unknown etiology received a larger number of immunotherapies (8 vs 5 patients; p = 0.02), were more often treated with the ketogenic diet (7 vs 2; p = 0.004) and were more likely to have a family history of epilepsy (6 vs 3; p = 0.045). The mean duration of RSE in the group with unknown etiology (12.25 h) was longer than in the group with etiology (4.25 h; p = 0.4). Fifty five percent of the patients with unknown etiology failed to return to baseline function at discharge compared to 36% in patients with an etiology (p = ns). Conclusions: One third of children with a first episode of RSE had an unknown etiology and seemed more likely to have a family history of epilepsy. These patients were more likely to receive immunotherapies and ketogenic diet.

Genetic and immune findings in complex febrile seizures and the epidemiology of Dravet syndrome: A nationwide cohort study.

Objectives: To determine what proportion of children presenting with complex febrile seizures (CFS) have an identifiable genetic mutation and/or serum anti-neuronal autoantibody positivity. To calculate the incidence of SCN1A-positive Dravet syndrome in Scotland. Methods: Patients were recruited from all 21 acute paediatric centres in the Scottish National Health Service over three-years (2014-2017). All children aged under three years (<3y) presenting with CFS were eligible. CFS was defined as any of: a cluster of two or more febrile seizures within a 24-hour period; any episode of febrile status epilepticus; two or more prolonged (>10 minute) febrile seizures within any time period. All children <3y presenting with new-onset epilepsy (n=167), afebrile status epilepticus (n= 6), or clusters of afebrile seizures (n=5) were recruited as a comparison group. All recruits had testing on a 104-gene epilepsy panel and serum antibodies to 10 neuronal epitopes (AMPA, CASPR2, GABAa, GABAb, Glycine, LGI1, NMDA, TAG, GAD,V GKC). Results: In 32 months, 70/260 (27%) of total recruited cases fulfilled our criteria for CFS, equal to 7% of total first febrile seizure presentations (400 per year in Scotland). Gene panel testing identified a pathogenic mutation in 6 CFS cases (8.6%). In all 6 the causative gene was SCN1A. A further 4 cases of SCN1A mutation were identified from the cohort presenting with epilepsy without antecedent febrile seizures. 9/10 SCN1A-positive cases had a clinical picture consistent with Dravet syndrome, making the incidence of SCN1A- positive Dravet syndrome in this population 1 in 16,600 live births. Anti-neuronal antibodies were identified in 10% of the CFS cohort, versus 14% of the epilepsy cohort. One of 10 SCN1A-positive patients also had antibodies(GABAa). Conclusion: The only major genetic epilepsy presenting initially with CFS is SCN1A- related. Most SCN1A-related epilepsy cases present initially with febrile seizures, but 40% have initial seizures that are afebrile. The incidence of SCN1A-positive Dravet syndrome is higher than previously reported.

Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.

Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. Analysis was performed on residual samples of children with FSE (n=33) aspart of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n=17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1β levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1β and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1β, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1β or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus

BackgroundEvidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. MethodsWe retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. ResultsThirty-five patients (23 boys; age range: 1–18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. ConclusionsOur results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes.

New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features.

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

Enduring Memory Impairments Provoked by Developmental Febrile Seizures Are Mediated by Functional and Structural Effects of Neuronal Restrictive Silencing Factor.

In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST). This transcriptional regulator is known to contribute to neuronal differentiation during development and to programmed gene expression in mature neurons. The mechanisms of the eFSE-provoked memory problems involved complex disruption of memory-related hippocampal oscillations recorded from CA1, likely resulting in part from impairments of dendritic filtering of cortical inputs as well as abnormal synaptic function. Accordingly, eFSE provoked region-specific dendritic loss in the hippocampus, and aberrant generation of excitatory synapses in dentate gyrus granule cells. Blocking NRSF transiently after eFSE prevented granule cell dysmaturation, restored a functional balance of γ-band network oscillations, and allowed treated eFSE rats to encode and retrieve spatial memories. Together, these studies provide novel insights into developing networks that underlie memory, the mechanisms by which early-life seizures influence them, and the means to abrogate the ensuing cognitive problems.SIGNIFICANCE STATEMENT Whereas seizures have been the central focus of epilepsy research, they are commonly accompanied by cognitive problems, including memory impairments that contribute to poor quality of life. These deficits often arise before the onset of spontaneous seizures, or independent from them, yet the mechanisms involved are unclear. Here, using a rodent model of common developmental seizures that provoke epilepsy in a subset of individuals, we identify serious consequent memory problems. We uncover molecular, cellular, and circuit-level mechanisms that underlie these deficits and successfully abolish them by targeted therapeutic interventions. These findings may be important for understanding and preventing cognitive problems in individuals suffering long febrile seizures.

Parental stress, pediatric quality of life, and behavior at baseline and one-year follow-up: Results from the FEBSTAT study.

From 2003 to 2010, 199 subjects, age 1 month to 5 years, were recruited as part of a prospective, multicenter study (FEBSTAT) of consequences of febrile status epilepticus (FSE). At one month and one year after the episode of FSE, parents were asked to complete the Parenting Stress Index, short form (PSI/SF), the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL). In addition to PedsQL and CBCL in the FEBSTAT subjects only, a comparison was made between Columbia Study of First Febrile Seizures subjects with a first simple febrile seizure (SFS) and the FEBSTAT group, including 15 subjects with FSE from the Columbia group, in the area of parental stress which was administered at the same time intervals in both studies. At baseline, the PSI/SF was statistically significantly higher for SFS versus FSE on the parent-child dysfunctional score and the total raw score, however at one year this difference resolved. In the FSE group, significantly higher parental stress over one year was reported in children with abnormal versus normal prior development (p= 0.02). Prior abnormal development was a risk factor at 1 year for lower total PEDSQL (p=0.01) versus prior normal development. Mean scores on the CBCL at baseline and 1 year were within the normal range for both empirically based scales and major risk factors. Parents of children experiencing a SFS experienced more stress at baseline than those with FSE. Families of children in the FEBSTAT cohort with identified development problems at baseline that continued, or progressed over the one year period, reported decreasing QOL.

Hydrogen Sulfide Promotes Learning and Memory and Suppresses Proinflammatory Cytokines in Repetitive Febrile Seizures

Objective: Hydrogen sulfide (H₂S), as a novel gasotransmitter, plays important roles in a number of physiological and pathological processes. Its effectiveness has been demonstrated in different types of brain disorders but not in repetitive febrile seizure (febrile status epilepticus; FSE) models. This study aims to test whether a donor of H₂S sodium sulfhydrate (NaHS) is also effective for FSE in rats. Methods: FSE was induced in rat pups on postnatal day 10 in water at 45.0 ± 0.1°C for 10 consecutive days with or without preadministration of NaHS. Following evaluation of the latency and duration of hyperthermic seizures, impairment in learning and memory was measured by the Morris water maze test. Moreover, alterations of the microglial response and the production of proinflammatory cytokines IL-1β and TNF-α were calculated in the hippocampus. Results: We found that NaHS significantly increased the latency and decreased the duration of hyperthermic seizures. Furthermore, NaHS-treated pups showed less impairment in learning and memory. In addition, NaHS inhibited FSE-induced microglial responses and suppressed the production of IL-1β and TNF-α in the hippocampus. Conclusion: NaHS appears to be effective for the treatment of FSE in infants and children, in part due to its anti-inflammatory action.

Cognitive functioning one month and one year following febrile status epilepticus.

The objective of this study was to determine early developmental and cognitive outcomes of children with febrile status epilepticus (FSE) one month and one year after FSE. One hundred ninety four children with FSE were evaluated on measures of cognition, receptive language, and memory as part of the FEBSTAT study and compared with 100 controls with simple febrile seizures (FSs). Children with FSE did not differ dramatically on tasks compared with FS controls at one month after FSE but demonstrated slightly weaker motor development (p=0.035) and receptive language (p=0.034) at one year after FSE. Performances were generally within the low average to average range. Within the FSE cohort, non-White children performed weaker on many of the tasks compared with Caucasian children. At the one-year visit, acute hippocampal T2 findings on MRI were associated with weaker receptive language skills (p=0.0009), and human herpes virus 6 or 7 (HHV6/7) viremia was associated with better memory performances (p=0.047). Febrile status epilepticus does not appear to be associated with significant cognitive impairment on early developmental measures, although there is a trend for possible receptive language and motor delay one year after FSE. Further follow-up, which is in progress, is necessary to track long-term cognitive functioning.

Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study.

The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum.

Diagnostic and prognostic factors for acute encephalopathy.

Acute encephalopathy has the possibility of sequelae. While early treatment is required to prevent the development of sequelae, differential diagnosis is of the utmost priority. The aim of this study was therefore to identify parameters that can facilitate early diagnosis and prediction of outcome of acute encephalopathy. We reviewed the medical charts of inpatients from 2005 to 2011 and identified 33 patients with febrile status epilepticus. Subjects were classified into an acute encephalopathy group (n=20) and a febrile convulsion group (n=13), and the parameters serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), ammonia (NH3 ), cerebrospinal fluid (CSF) tau protein, and CSF interleukin-6 compared between them. Furthermore, the relationship between each parameter and prognosis was investigated in the encephalopathy group. Significant differences in serum AST, ALT, and LDH were observed between the febrile convulsion and acute encephalopathy group. Moreover, a significant difference in serum LDH was noted between the patients with and without developmental regression at the time of hospital discharge in the encephalopathy group. In particular, CSF tau protein was found to be highly likely to indicate progress, with CSF tau protein >1000pg/dL associated with poor prognosis leading to developmental regression. Serum AST, ALT and LDH may be related to early diagnosis and prognosis, and should be carefully investigated in patients with encephalopathy. CSF tau protein could also be used as an indicator of poor prognosis in acute encephalopathy.

How Different Are the Patients With Bilateral Hippocampal Sclerosis From the Unilateral Ones Clinically?

There is a lack of knowledge on consecutive patients with epilepsy associated with bilateral hippocampal sclerosis (BHS). We aimed to investigate the differentiating features of BHS in comparison with unilateral HS (UHS). We investigated our database for patients with epilepsy fulfilling the major magnetic resonance imaging criteria for BHS; namely, presence of bilateral atrophy and high signal changes on T2 and FLAIR series in the hippocampi. UHS patients seen in past 2 years were included as the control group. Clinical, EEG, and other laboratory findings, data on treatment response and epilepsy surgery were investigated from their files. A total of 124 patients (31 with BHS and 93 with UHS; 49 right-sided and 44 left-sided) were included. We found that 16.1% of the BHS and 18.3% of the UHS groups were not drug-refractory. A binary logistic regression analysis performed with significant clinical features disclosed that history of febrile status epilepticus, mental retardation, and status epilepticus were statistically more common in BHS group. Moreover, diagnosis of psychosis established by an experienced psychiatrist and slowing of the EEG background activity were both found significantly more frequent in BHS. 66.67% of the operated BHS patients showed benefit from epilepsy surgery. BHS is a heterogeneous group, showing significant differences such as increased frequencies of mental retardation, status epilepticus, febrile status epilepticus and psychosis, in comparison to UHS. In all, 16.1% of the BHS cases showed a benign course similar to the UHS group and some patients with drug-resistant epilepsy may show benefit from epilepsy surgery.

Risk factors for subsequent febrile seizures in the FEBSTAT study.

To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile seizure (SFS). To identify home use of rescue medications for subsequent FS. Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5-year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS. Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4-fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio [HR] 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting ≥10 min. Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE.

Helping Families Cope with the Severe Stress of Dravet Syndrome.

A child with Dravet syndrome shakes family life to the core. Dravet syndrome usually has three phases: (1) up to 1-1½ years: with episodes of febrile status epilepticus but normal development; (2) age 1½ to ~6-10 years: with frequent seizures of varying types, developmental stagnation, behavioural and sleep problems; (3) after ~10 years: improvement in seizures, deteriorating gait, intellectual disability but some developmental gains. Complete seizure control is rare-simply prescribing medication is inadequate to help families. Based on structured interviews with 24 families and confirmed by more informal discussions with other families, we suggest strategies for coping with this catastrophe. A child with Dravet syndrome usually means that one parent cannot work-financial pressures should be anticipated. In Stage 1, the approach to status should include a written protocol. An indwelling catheter for rapid venous access may be helpful. In Stage 2, assistance finding qualified babysitters is required, and the extended family needs encouragement to help. Appropriate equipment, rescue medication and protocols should travel with the child. Siblings may benefit from a system of one parent "on call." An internet support group provides an invaluable lifeline. In Stage 3, family isolation may be extreme-respite care and personal time for parents are important. Death from status, accidents and SUDEP (sudden unexplained death in epilepsy) occurs in 15%. Fear of SUDEP needs to be addressed. Moving from paediatric to adult care is frightening; an epilepsy transition clinic is useful. Attention to these realities may improve the quality of life for both child and family.

Early Life Seizures and Learning Impairment: Neither the Time nor the Place

Early Life Seizures and Learning Impairment: Neither the Time nor the Place

Temporal Coordination of Hippocampal Neurons Reflects Cognitive Outcome Post-febrile Status Epilepticus

The coordination of dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes. Conversely, cognitive deficits that occur following neurological insults may result from network discoordination. We hypothesized that cognitive outcome following febrile status epilepticus (FSE) depends on network efficacy within and between fields CA1 and CA3 to dynamically organize cell activity by theta phase. Control and FSE rats were trained to forage or perform an active avoidance spatial task. FSE rats were sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). FSE-NL CA1 place cells did not exhibit phase preference in either context and exhibited poor cross-theta interaction between CA1 and CA3. FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. Temporal coordination of neuronal activity by theta phase may therefore explain variability in cognitive outcome following neurological insults in early development.

Pharmacotherapy for Dravet Syndrome.

Dravet syndrome (DS) is an intractable pediatric epilepsy syndrome, starting in early childhood. This disorder typically manifests with febrile status epilepticus, and progresses to a multifocal epilepsy with febrile and non-febrile seizures with encephalopathy. Most cases are due to a mutation in the SCN1A gene. This article reviews treatments for DS, with an emphasis on pharmacotherapy. While many medications are used in treating the seizures associated with DS, these patients typically have medically refractory epilepsy, and polytherapy is often required. First-line agents include valproate and clobazam, although there are supportive data for topiramate, levetiracetam, stiripentol and the ketogenic diet. Other agents such as fenfluramine are promising therapies for Dravet syndrome. Sodium channel-blocking anticonvulsants such as carbamazepine and lamotrigine are generally contraindicated in this syndrome. Nonpharmacologic therapies (such as neurostimulation or surgery) are understudied in DS. Because DS is a global encephalopathy, pharmacologic treatment of non-epileptic manifestations of the disease is often necessary. Attention-deficit hyperactivity disorder is often encountered in patients with DS, and psychostimulants can be helpful for this indication. Other psychoactive drugs are less studied in this context. Extrapyramidal and gait disorders are often encountered in DS as well. While DS is a severe epileptic encephalopathy with a high (up to 15%) mortality rate in childhood, careful pharmacologic management can improve these patients' clinical picture and quality of life.

Status Epilepticus.

Although the majority of seizures are brief and cause no long-term consequences, a subset is sufficiently prolonged that long-term consequences can result. These very prolonged seizures are termed "status epilepticus" (SE) and are considered a neurological emergency. The clinical presentation of SE can be diverse. SE can occur at any age but most commonly occurs in the very young and the very old. There are numerous studies on SE in animals in which the pathophysiology, medication responses, and pathology can be rigorously studied in a controlled fashion. Human data are consistent with the animal data. In particular, febrile status epilepticus (FSE), a form of SE common in young children, is associated with injury to the hippocampus and subsequent temporal lobe epilepsy (TLE) in both animals and humans.

Etiology and outcome of infants and children in a tertiary hospital in the Philippines with convulsive status epilepticus

Introduction: Among the paediatric neurological disorder, seizure ranks first. Status Epilepticus (SE) is a neurological emergency. It is associated with significant morbidity and mortality. The objectives of the presented study were to determine the clinical profile and outcome of status epilepticus in infant and children at a tertiary care hospital in Philippines. Methodology: It was a retrospective study conducted in Department of Pediatrics, National Children's Hospital, Quezon City, Philippines. All the patients in the age range 1 month to 18 years, admitted and diagnosed as cases of SE between January 2008 to December 2014 formed the sample size. Results: The seven-year average hospital based incidence of SE was 138.5 per 100,000 admissions. The most common underlying cause of SE was seizure disorder (29.89%), followed by bacterial meningitis (13.8%), and cerebral palsy (10.3%). Conclusion: Febrile SE is the common form of convulsive SE. There is high morbidity and mortality associated with SE.

Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics

We studied the efficacy of drugs indicated for mitochondrial dysfunction in the treatment of 21 patients with acute encephalopathy with onset of febrile convulsive status epilepticus at our hospital from January 2006 to December 2014. Among them, 11 patients had been treated with a mitochondrial drug cocktail consisting of vitamin B1, vitamin C, biotin, vitamin E, coenzyme Q10, and l-carnitine (prescription group) and 10 patients were not treated with the cocktail (non-prescription group). We retrospectively reviewed age, trigger, clinical form, treatment start time, and sequelae. Clinical form was classified into a biphasic group presenting acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and a monophasic group. Sequelae were classified as (A) no sequelae group or (B) sequelae group, and differences in the interval between diagnosis and treatment were also evaluated. The sequelae were not different between the mitochondrial drug cocktail prescription and non-prescription groups, but significantly better in the group administered the mitochondrial drug cocktail within 24h (P=0.035). We expect that early treatment with a mitochondrial drug cocktail could prevent sequelae in acute encephalopathy with onset of febrile convulsive status epilepticus.