OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION--The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves.
Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE.
We collected data prospectively on children in north London, UK, who had episodes of CSE (ascertainment 62–84%). The factors associated with seizure termination after first-line and second-line therapies, episodes of CSE lasting for longer than 60 min, and respiratory depression were analysed with logistic regression. Analysis was per protocol, and adjustment was made for repeat episodes in individuals.
182 children of median age 3·24 years (range 0·16–15·98 years) were included in the North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) between May, 2002, and April, 2004. 61% (147) of 240 episodes were treated prehospital, of which 32 (22%) episodes were terminated. Analysis with multivariable models showed that treatment with intravenous lorazepam (n=107) in the accident and emergency department was associated with a 3·7 times (95% CI 1·7–7·9) greater likelihood of seizure termination than was treatment with rectal diazepam (n=80). Treatment with intravenous phenytoin (n=32) as a second-line therapy was associated with a 9 times (95% CI 3–27) greater likelihood of seizure termination than was treatment with rectal paraldehyde (n=42). No treatment prehospital (odds ratio [OR] 2·4, 95% CI 1·2–4·5) and more than two doses of benzodiazepines (OR 3·6, 1·9–6·7) were associated with episodes that lasted for more than 60 min. Treatment with more than two doses of benzodiazepines was associated with respiratory depression (OR 2·9, 1·4–6·1). Children with intermittent CSE arrived at the accident and emergency department later after seizure onset than children with continuous CSE did (median 45 min [range 11–514 min] vs 30 min [5–90 min]; p<0·0001, Mann-Whitney U test); for each minute delay from onset of CSE to arrival at the accident and emergency department there was a 5% cumulative increase in the risk of the episode lasting more than 60 min.
These data add to the debate on optimum emergency treatment of childhood CSE and suggest that the current guidelines could be updated.
An anonymous donor to UCL Institute of Child Health; the Wellcome Trust; UK Department of Health National Institute for Health Research Biomedical Research Centres Funding Scheme; Medical Research Council.
Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus.
Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus.
In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.
Convulsive status epilepticus (CSE) is the most common neurological emergency in childhood and is often associated with fever. In sub-Saharan Africa, the high incidence of febrile illnesses might influence the incidence and outcome of CSE. We aimed to provide data on the incidence, causes, and outcomes of childhood CSE in this region.
Between March, 2006, and June, 2006, we studied all children who had been admitted with CSE to a Kenyan rural district hospital in 2002 and 2003. Confirmed CSE had been observed directly; probable CSE was inferred from convulsions on arrival, requirement for phenobarbital or phenytoin, or coma with a recent history of seizures. We estimated the incidence with linked demographic surveillance, and risk factors for death and neurological sequelae were analysed by multivariable analysis.
Of 388 episodes of CSE, 155 (40%) were confirmed CSE and 274 (71%) were caused by an infection. The incidence of confirmed CSE was 35 (95% CI 27–46) per 100 000 children per year overall, and was 52 (21–107) and 85 (62–114) per 100 000 per year in children aged 1–11 months and 12–59 months, respectively. The incidence of all CSE was 268 (188–371) and 227 (189–272) per 100 000 per year in these age-groups. 59 (15%) children died in hospital, 81 (21%) died during long-term follow-up, and 46 (12%) developed neurological sequelae. Mortality of children with confirmed CSE while in hospital was associated with bacterial meningitis (adjusted relative risk [RR]=2·6; 95% CI 1·4–4·9) and focal onset seizures (adjusted RR=2·4; 1·1–5·4), whereas neurological sequelae were associated with hypoglycaemia (adjusted RR=3·5; 1·8–7·1) and age less than 12 months (adjusted RR=2·5; 1·2–5·1).
Prevention of infections and appropriate early management of seizures might reduce the incidence and improve the outcome of CSE in children in sub-Saharan Africa.
To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort.
Patients and Methods
We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant.
We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure.
Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE.
Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.
The aim of the study was to review the epidemiology, clinical profile and discuss the etiology, prognosis and treatment options in patients aged 60 years or older presenting with status epilepticus. We performed a systematic review involving studies published from 1996 to 2010, in Medline/PubMed, Scientific Electronic Library on line (Scielo), Latin-American and Caribbean Center of Health Sciences Information (Lilacs) databases and textbooks. Related articles published before 1996, when relevant for discussing epilepsy in older people, were also included. Several population studies had shown an increased incidence of status epilepticus after the age of 60 years. Status epilepticus is a medical and neurological emergency that is associated with high morbidity and mortality, and is a major concern in the elderly compared to the general population. Prompt diagnosis and effective treatment of convulsive status epilepticus are crucial to avoid brain injury and reduce the fatality rate in this age group.
case fatality; elderly; epidemiology; epilepsy; status epilepticus; treatment.
Generalised convulsive status epilepticus continues to be a medical emergency with high morbidity and mortality. The patient with convulsive status epilepticus has continuous or rapidly repeating seizures. In contrast, symptoms in nonconvulsive status epilepticus are often more subtle which frequently delays the diagnosis. This case describes a 27 year-old man who presented after a first seizure and only displayed symptoms of slight bradyphrenia. An electroencephalogram revealed a generalised status epilepticus. As nonconvulsive status epilepticus may clinically display only subtle symptoms a high index of suspicion is needed to initiate electroencephalographic studies.
Aims: In children with convulsive status epilepticus (CSE) with fever, to determine the likelihood of acute bacterial meningitis (ABM), the proportion that are treated with antibiotics, and the proportion that have diagnostic CSF sampling.
Methods: Patients with an incident episode of CSE with fever were identified as part of an ongoing prospective population based study of CSE in childhood.
Results: There were 49 incident cases of CSE in the first six months. Ascertainment was 96%. Twenty four had CSE with fever, 16 had early parenteral antibiotics, nine had diagnostic CSF sampling, and four had ABM. The population risk of ABM in CSE with fever was significantly higher than that of short seizures with fever (17% v 1.2%).
Conclusions: The classical symptoms and signs of ABM may be absent in CSE with fever. A high index of suspicion for ABM in the child with CSE with fever is paramount. The most appropriate management is suggested to be early parenteral antibiotics and a lumbar puncture when there are no contraindications.
To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus?
We used a decision model to evaluate the risks and benefits of treating non-convulsive status epilepticus with intravenous anesthetics and ICU-level aggressive care. We investigated how the decision to use aggressive versus non-aggressive management for non-convulsive status epilepticus impacts expected patient outcome for four etiologies: absence epilepsy, discontinued antiepileptic drugs, intraparenchymal hemorrhage, and hypoxic ischemic encephalopathy. Each etiology was defined by distinct values for five key parameters: baseline mortality rate of the inciting etiology; efficacy of non-aggressive treatment in gaining control of seizures; the relative contribution of seizures to overall mortality; the degree of excess disability expected in the case of delayed seizure control; and the mortality risk of aggressive treatment.
Non-aggressive treatment was favored for etiologies with low morbidity and mortality such as absence epilepsy and discontinued antiepileptic drugs. The risk of aggressive treatment was only warranted in etiologies where there was significant risk of seizure-induced neurologic damage. In the case of post-anoxic status epilepticus, expected outcomes were poor regardless of the treatment chosen. The favored strategy in each case was determined by strong interactions of all five model parameters.
Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology.
Non-convulsive status epilepticus; Risk benefit analysis; NCSE; Decision analysis
Status epilepticus can complicate any type of seizure activity. A group of 13 children with non-convulsive status has been studied. Five presented with chronic fluctuating neurological features, while eight had intermittent episodes of their atypical status, although each of these lasted for several days. The clinical features, treatment, and outcome for these groups of children are described. Most of the children in both groups are mentally retarded after regressing at the time of their status epilepticus. The recognition and aggressive treatment of atypical status is important in reducing the risk of subsequent mental handicap.
Nonconvulsive status epilepticus (NCSE) comprises a group of syndromes that display a great diversity regarding response to anticonvulsants ranging from virtually self-limiting variants to entirely refractory forms. Therefore, treatment on intensive care units (ICUs) is required only for a selection of cases. The aetiology and clinical form of NCSE are strong predictors for the overall prognosis. Absence status epilepticus is commonly seen in patients with idiopathic generalized epilepsy and is rapidly terminated by low-dose of benzodiazepines. The management of complex partial status epilepticus is straightforward in patients with pre-existing epilepsy, but poses major problems if occurring in the context of acute brain lesions. Subtle status epilepticus represents the late stage of undertreated previous overt generalized convulsive status epilepticus and always requires aggressive ICU treatment. Within the intensive care setting, the diagnostic challenge may be seen in the difficulty in delineating nonepileptic conditions such as posthypoxic, metabolic or septic encephalopathies from NCSE. Although all important forms are considered, the focus of this review lies on clinical presentations and electroencephalogram features of comatose patients treated on ICUs and possible diagnostic pitfalls.
anticonvulsant treatment; diagnostic pitfalls; electroencephalogram patterns; encephalopathies; nonconvulsive status epilepticus
Epilepsy is common in sub-Saharan Africa but is poorly characterized. Most studies are hospital-based, and may not reflect the situation in rural areas with limited access to medical care. We examined people with active convulsive epilepsy (ACE), to determine if the clinical features could help elucidate the causes.
We conducted a detailed descriptive analysis of 445 people with ACE identified through a community-based survey of 151,408 people in rural Kenya, including the examination of electroencephalograms.
Approximately half of the 445 people with ACE were children or adolescents. Seizures began in childhood in 78% of those diagnosed. An episode of status epilepticus was recalled by 36% cases, with an episode of status epilepticus precipitated by fever in 26%. Overall 169 had an abnormal electroencephalogram, 29% had focal features, 34% had epileptiform activity. In the 146 individuals who reported generalised tonic-clonic seizures only, 22% had focal features on their electroencephalogram. Overall 71% of patients with ACE had evidence of focal abnormality, documented by partial onset seizures, focal neurological deficits or focal abnormalities on the electroencephalogram. Increased seizure frequency was strongly associated with age and cognitive impairment in all ages and non-attendance at school in children (p < 0.01).
Children and adolescents bear the brunt of epilepsy in a rural population in Africa. The predominance of focal features and the high proportion of patients with status epilepticus, suggests that much of the epilepsy in this region has identifiable causes, many of which could be prevented.
epilepsy; convulsions; partial seizures; electroencephalogram; status epilepticus; sub-Saharan Africa
Mutations in the gene encoding of the catalytic subunit of mtDNA polymerase gamma (POLG1) can cause typical Alpers' syndrome. Recently, a new POLG1 mutation phenotype was described, the so-called juvenile-onset Alpers' syndrome. This POLG1 mutation phenotype is characterized by refractory epilepsy with recurrent status epilepticus and episodes of epilepsia partialis continua, which often necessitate admission to the intensive care unit (ICU) and pose an important mortality risk. We describe two previously healthy unrelated teenage girls, who both were admitted with generalized tonic-clonic seizures and visual symptoms leading to a DNA-supported diagnosis of juvenile-onset Alpers' syndrome. Despite combined treatment with anti-epileptic drugs, both patients developed status epilepticus requiring admission to the ICU. Intravenous magnesium as anti-convulsant therapy was initiated, resulting in clinical and neurophysiological improvement and rapid extubation of both patients. Treating status epilepticus in juvenile-onset Alpers' syndrome with magnesium has not been described previously. Given the difficulties encountered while treating epilepsy in patients with this syndrome, magnesium therapy might be considered.
Alpers' syndrome; POLG1; Magnesium; Status epilepticus; Adolescence
AIM—To evaluate the likelihood that, in children under the age of 2 years, convulsions alone may cause retinal haemorrhages.
METHODS—Children under the age of 2 years admitted to hospital following convulsions, were examined within 48 hours of admission. The convulsions were classified by a paediatric neurologist and detailed ocular examination, including indirect ophthalmoscopy, was performed by an ophthalmologist. Statistical analysis was undertaken using Hanley's rule of three.
RESULTS—32 consecutive children admitted with convulsions were examined; 10 of them were admitted following epileptic seizures and 22 following febrile convulsions. Two of the children with febrile convulsions were admitted in status epilepticus. None of these children had retinal haemorrhages. Therefore, using Hanley's rule of three, the upper limit of 95% confidence interval of retinal haemorrhages following convulsions in children under the age of 2 years, is less than 10/100.
CONCLUSIONS—In children under the age of 2 years convulsions alone are unlikely to cause retinal haemorrhages. By combining the results of this study with those previously reported from this unit in older children, the upper limit of 95% confidence interval of retinal haemorrhages, following convulsions in children under the age of 14 years, is less than 5/100. Therefore, the finding of retinal haemorrhages in a child admitted with a history of convulsion should trigger a meticulous search for other causes of these haemorrhages, particularly non-accidental injury.
Keywords: convulsions; retinal haemorrhages; non-accidental injury; infants
Transient elevation of serum prolactin frequently follows generalised tonic-clonic and complex partial seizures. However, the levels of prolactin during status epilepticus are not increased above the normal range. Exhaustion of central prolactin supplies has been proposed as a possible mechanism for the absence of prolactin increase during status epilepticus. To test this hypothesis we injected intravenous metoclopramide (10 mg) in eight consecutive patients with status epilepticus. One patient had generalised tonic-clonic status epilepticus. Seven patients had EEG-verified non-convulsive status epilepticus, consisting of one typical absence status, one atypical absence status and five complex partial status epilepticus. Metoclopramide raised the mean (SD) prolactin levels at least five-fold in all patients, from 5.8 (8.0) micrograms/l to 87.0 (39.0) micrograms/l, within 60 minutes after the injection. Thus the mechanism for low prolactin values in status epilepticus is not cellular depletion of stored prolactin, but more likely an altered regulation, presumably induced by prolonged seizure activity.
Intravascular lymphoma (IVL) is a rare disease form of malignant lymphoma, and it is characterised by the selective growth of lymphoma cells within the lumina of vessels. Identification of this disease at an early stage is difficult because of non-specific clinical symptoms and neuroradiological findings. Most reported IVL cases are diagnosed at post-mortem following autopsy. We report the case of a patient who presented with status epilepticus (SE) as the initial manifestation of IVL. Despite the administration of anti-convulsant agents and general care the patient's condition deteriorated rapidly after admission, culminating in death due to respiratory failure and heart failure 21 days after the onset of symptoms. Post-mortem examination revealed IVL in the brain and multiple organs. Epileptic seizures often appear during the clinical course of IVL; however, they occur most frequently at advanced stages. Diagnosis of IVL that first presents with SE is of clinical importance because the treatment and prognosis of acute SE arising from IVL are different from those of SE originating from other causes.
Status epilepticus; Intravascular lymphoma; Diffusion-weighted imaging
Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.
Status epilepticus; Sprague-Dawley rats; Pilocarpine; Age; Mortality; Development; Senescence
Rat hippocampal area CA3 pyramidal cells synchronously discharge in rhythmic bursts of action potentials after acute disinhibition or convulsant treatment in vitro. These burst discharges resemble epileptiform activity, and are of interest because they may shed light on mechanisms underlying limbic seizures. However, few studies have examined CA3 burst discharges in an animal model of epilepsy, because a period of prolonged, severe seizures (status epilepticus) is often used to induce the epileptic state, which can lead to extensive neuronal loss in CA3. Therefore, the severity of pilocarpine-induced status epilepticus was decreased with anticonvulsant treatment to reduce damage. Rhythmic burst discharges were recorded in the majority of slices from these animals, between two weeks and nine months after status epilepticus. The incidence and amplitude of bursts progressively increased with time after status, even after spontaneous behavioral seizures had begun. The results suggest that modifying the pilocarpine models of temporal lobe epilepsy to reduce neuronal loss leads to robust network synchronization in area CA3. The finding that these bursts increase long after spontaneous behavioral seizures begin supports previous arguments that temporal lobe epilepsy exhibits progressive pathophysiology.
status epilepticus; hippocampal slice electrophysiology; paroxysmal depolarizing shift; temporal lobe epilepsy
To characterize children with new-onset seizures presenting as status epilepticus at a tertiary care children's hospital.
Prospectively collected data were reviewed from a database derived from a mandated critical care pathway. A total of 1,382 patients presented with new-onset seizures between 2001 and 2007.
A total of 144 patients presented in status epilepticus. The average age was 3.4 years. The majority of seizures (72%) lasted between 21 and 60 minutes. The majority of patients had no significant past medical history; one-fourth had a family history of epilepsy. Five (4%) patients with EEGs had electrographic seizures during the study, captured only with prolonged monitoring. The most common etiology was febrile convulsion, followed by cryptogenic. The most common acute symptomatic cause was CNS infection; the most common remote symptomatic cause was cerebral dysgenesis. Combined CT and MRI provided a diagnosis in 30%. CT was helpful in identifying acute vascular lesions and acute edema, whereas MRI was superior in identifying subtle abnormalities and remote symptomatic etiologies such as dysplasia and mesial temporal sclerosis.
Children who present in status epilepticus that is not a prolonged febrile convulsion should undergo neuroimaging in the initial evaluation. For any child who presents in status epilepticus and has not yet returned to baseline, the possibility of nonconvulsive status epilepticus should be considered. Although CT is often more widely accepted, especially in the urgent setting, strong consideration for MRI should be given when available, due to the superior yield.
= convulsive status epilepticus;
= head CT;
= nonconvulsive status epilepticus;
= status epilepticus.
Status epilepticus is a clinical emergency that can lead to the development of acquired epilepsy following neuronal injury. Understanding the pathophysiological changes that occur between the injury itself and the expression of epilepsy is important in the development of new therapeutics to prevent epileptogenesis. Currently, no anti-epileptogenic agents exist; thus, the ability to treat an individual immediately after status epilepticus to prevent the ultimate development of epilepsy remains an important clinical challenge. In the Sprague–Dawley rat pilocarpine model of status epilepticus-induced acquired epilepsy, intracellular calcium has been shown to increase in hippocampal neurons during status epilepticus and remain elevated well past the duration of the injury in those animals that develop epilepsy. This study aimed to determine if such changes in calcium dynamics exist in the hippocampal culture model of status epilepticus-induced acquired epilepsy and, if so, to study whether manipulating the calcium plateau after status epilepticus would prevent epileptogenesis. The in vitro status epilepticus model resembled the in vivo model in terms of elevations in neuronal calcium concentrations that were maintained well past the duration of the injury. When used following in vitro status epilepticus, dantrolene, a ryanodine receptor inhibitor, but not the N-methyl-d-aspartic acid channel blocker MK-801 inhibited the elevations in intracellular calcium, decreased neuronal death and prevented the expression of spontaneous recurrent epileptiform discharges, the in vitro correlate of epilepsy. These findings offer potential for a novel treatment to prevent the development of epileptiform discharges following brain injuries.
calcium dynamics; cultured hippocampal neurons; epileptogenesis; Fura-2; patch-clamp electrophysiology; rat
Prolonged seizures (status epilepticus) are associated with brain region-specific regulation of apoptosis-associated signaling pathways. Bcl-2 homology domain 3-only (BH3) members of the Bcl-2 gene family are of interest as possible initiators of mitochondrial dysfunction and release of apoptogenic molecules after seizures. Previously, we showed expression of the BH3-only protein Bim increased in the rat hippocampus but not neocortex following focal-onset status epilepticus. Here, we examined Bim expression in mice and compared seizure-damage between wild-type and Bim-deficient animals. Status epilepticus induced by intra-amygdala kainic acid caused extensive neuronal death within the ipsilateral hippocampal CA3 region. Hippocampal activation of factors associated with transcriptional and post-translational activation of Bim, including CHOP and c-Jun NH(2)-terminal kinases, was significant within 1 h. Up-regulation of bim mRNA was evident after 2 h and Bim protein was increased from 4–24 h. Hippocampal CA3 neurodegeneration was reduced in Bim-deficient mice compared to wild-type animals following seizures in vivo, and short interfering RNA molecules targeting bim reduced cell death following kainic acid treatment of hippocampal organotypic cultures. In contrast, neocortical Bim expression declined after status epilepticus and neocortex damage in Bim-deficient mice was comparable to wild-type animals. These results demonstrate region-specific differential contributions of Bim to seizure-induced neuronal death.
Apoptosis; Bax; Bcl-2; FKHR; Hippocampus; JNK; Neuroprotection; Temporal lobe epilepsy
To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE.
Ten hospitals in the Pediatric Emergency Care Applied Research Network (PECARN) enlisted patients 3 months to 17 years with convulsive SE (STATUS) or for a traditional PK study (ELECTIVE). Sparse sampling was used for STATUS and intensive sampling for ELECTIVE. Noncompartmental analyses were performed on ELECTIVE, and served to nest compartmental population PK analysis for both cohorts.
48 STATUS and 15 ELECTIVE patients were enrolled. Median age was 7 years, 2 months. The population PK parameters were: clearance 1.2 mL/min/kg, half-life 16.8 hours, volume of distribution 1.5 L/kg. Based on the PK model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations above 30–50 ng/mL for 6–12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg.
Lorazepam PK in convulsive status epilepticus is similar to previous PK measured in pediatric patients with cancer, except for longer half-life and similar to adult PK parameters except for increased clearance.
Non-convulsive status epilepticus may present as confusion, behavioural disturbances and psychiatric conditions. We present the case of a 17-year-old man who had episodes of non-convulsive status epilepticus as his only manifestation of epilepsy which was mis-diagnosed as a psychiatric condition for over 10 years. He has had almost complete resolution of his symptoms with the introduction of carbamazepine. Non-convulsive status epilepticus is probably commoner than previously thought, and should be considered as a possible diagnosis in all patients presenting with prolonged episodes of altered consciousness even without other manifestations of epilepsy.
Refractory status epilepticus (RSE) can be defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and etiology (that should be actively targeted). Recent recommendations for adults, relying upon limited evidence, suggest that RSE treatment aggressiveness should be tailored to the clinical situation: to minimize ICU-related complications, focal RSE without major consciousness impairment might initially be approached more conservatively; conversely, early induction of pharmacological coma is advisable in generalized-convulsive forms. At this stage, midazolam, propofol or barbiturates represent the most used alternatives. Several other treatments, such as additional anesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (electroconvulsive treatment, hypothermia), have been used in protracted RSE. Treatment lasting weeks or months may sometimes result in a good outcome, as in selected cases after cerebral anoxia and encephalitis. Well-designed prospective studies of this condition are urgently needed.
treatment; therapy; outcome; prognosis; risk; benzodiazepines; barbiturates; propofol; research
Seizures are not an uncommon occurrence in older adults, and the incidence of status epilepticus is much greater in the elderly than in younger populations. Status epilepticus is a neurologic emergency and requires prompt intervention to minimize morbidity and mortality. Treatment involves both supportive care as well as initiation of medications to stop all clinical and electrographic seizure activity. Benzodiazepines are used as first-line agents, followed by antiepileptic drugs when seizures persist. In refractory status epilepticus, urgent neurologic consultation is indicated for the titration of anesthetic agents to a level of appropriate background suppression on EEG. In light of our aging population, physician awareness and competence in the management of status epilepticus is imperative and should be recognized as a growing public health concern.
status epilepticus; convulsive; generalized; nonconvulsive; refractory; elderly; treatment