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1.  Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study. 
BMJ : British Medical Journal  1993;307(6898):225-228.
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.
PMCID: PMC1678165  PMID: 8369681
2.  Risk Factors Associated with Death in In-Hospital Pediatric Convulsive Status Epilepticus 
PLoS ONE  2012;7(10):e47474.
Objective
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0047474
PMCID: PMC3482185  PMID: 23110074
3.  Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study 
Lancet Neurology  2008;7(8):696-703.
Summary
Background
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.
Methods
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.
Results
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.
Interpretation
These data add to the debate on optimum emergency treatment of childhood CSE and suggest that the current guidelines could be updated.
Funding
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.
doi:10.1016/S1474-4422(08)70141-8
PMCID: PMC2467454  PMID: 18602345
4.  Nonconvulsive status epilepticus manifesting as bradyphrenia: a case report 
Cases Journal  2009;2:7069.
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.
doi:10.4076/1757-1626-2-7069
PMCID: PMC2740199  PMID: 19829903
5.  Status epilepticus in the elderly: epidemiology, clinical aspects and treatment 
Neurology International  2012;4(3):e17.
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.
doi:10.4081/ni.2012.e17
PMCID: PMC3555219  PMID: 23355930
case fatality; elderly; epidemiology; epilepsy; status epilepticus; treatment.
6.  Calculating the Risk Benefit Equation for Aggressive Treatment of Non-convulsive Status Epilepticus 
Neurocritical care  2013;18(2):216-227.
Objective
To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus?
Method
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.
Results
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.
Conclusions
Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology.
doi:10.1007/s12028-012-9785-y
PMCID: PMC3767472  PMID: 23065689
Non-convulsive status epilepticus; Risk benefit analysis; NCSE; Decision analysis
7.  Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report 
Introduction
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.
Case presentation
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.
Conclusions
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.
doi:10.1186/1752-1947-5-432
PMCID: PMC3179759  PMID: 21892965
8.  Epilepsy-Related Mortality is Low in Children: A 30 Year Population-Based Study in Olmsted County, MN 
Epilepsia  2012;53(12):2164-2171.
Purpose
Epilepsy is a common childhood neurologic disorder, affecting 0.5 to1% of children. Increased mortality occurs due to progression of underlying disease, seizure-related accidents, suicide, status epilepticus, aspiration during seizures, and sudden unexplained death in epilepsy (SUDEP). Previous studies show mortality rates of 2.7 to 6.9 per 1000 person-years (Berg et al., 2004, Sillanpaa & Shinnar, 2010). Potential risk factors include poor seizure control, intractable epilepsy, status epilepticus, tonic-clonic seizures, mental retardation, and remote symptomatic cause of epilepsy (Berg et al., 2004, Sillanpaa & Shinnar, 2010, Walczak et al., 2001). Few population-based studies of mortality and SUDEP in childhood-onset epilepsy have been published. The purpose of this study is to report mortality and SUDEP from a 30 year population-based cohort of children with epilepsy.
Methods
The Medical Diagnostic Index of the Rochester Epidemiology Project was searched for all codes related to seizure and convulsion in children living in Olmsted County, Minnesota and of ages birth through 17 years from 1980 through 2009. The medical records of these children were reviewed to identify all those with new-onset epilepsy, and to abstract other baseline and follow-up information. Potential risk factors including seizure type, epilepsy syndrome, history of status epilepticus, the presence and severity of neurologic impairment, and epilepsy outcome was reviewed. Epilepsy outcome was characterized by seizure frequency, number of anti-seizure medications (AEDs) used, and number of AEDs failed due to lack of efficacy, and epilepsy intractability at 1, 2, 3, 5, 10, 15, and 20 years after epilepsy onset. We followed all children through their most recent visit to determine vital status, cause of death, and whether autopsy was performed.
Key Findings
From 1980 to 2009, there were 467 children age birth through 17 years diagnosed with epilepsy while residents of Olmsted County, MN and had follow-up beyond the time of epilepsy diagnosis. Children were followed for a median of 7.87 years after the time of diagnosis (range 0.04–29.49 years) for a total of 4558.5 person-years. Sixteen (3.4%) of the children died, or 3.51 deaths per 1000 person-years. Two deaths were epilepsy-related (12.5%) for a rate of 0.44 per 1000 person years. One of these children died of probable SUDEP and one died of aspiration during a seizure. The remaining 14 deaths (87.5%) were due to other complications of underlying disease. Several risk factors for mortality were found, including abnormal cognition, abnormal neurologic exam, structural/metabolic etiology for epilepsy, and poorly controlled epilepsy.
doi:10.1111/j.1528-1167.2012.03661.x
PMCID: PMC3766953  PMID: 22989286
9.  Can convulsions alone cause retinal haemorrhages in infants? 
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
PMCID: PMC1722626  PMID: 9797668
10.  Propofol Infusion Syndrome in Refractory Status Epilepticus 
Journal of Epilepsy Research  2013;3(1):21-27.
Background and Purpose:
Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus.
Methods:
This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups.
Results:
There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O.
Conclusions:
RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE.
doi:10.14581/jer.13004
PMCID: PMC3957310  PMID: 24649467
Propofol infusion syndrome; Status Epilepticus; Anesthetics
11.  Meningitis is a common cause of convulsive status epilepticus with fever 
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.
doi:10.1136/adc.2003.038844
PMCID: PMC1720095  PMID: 15613516
12.  Incidence and outcome of convulsive status epilepticus in Kenyan children: a cohort study 
Lancet Neurology  2008;7(2):145-150.
Summary
Background
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.
Methods
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.
Findings
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).
Interpretation
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.
doi:10.1016/S1474-4422(07)70331-9
PMCID: PMC2258310  PMID: 18248771
13.  Nonconvulsive status epilepticus: a diagnostic and therapeutic challenge in the intensive care setting 
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.
doi:10.1177/1756285611403826
PMCID: PMC3105634  PMID: 21694817
anticonvulsant treatment; diagnostic pitfalls; electroencephalogram patterns; encephalopathies; nonconvulsive status epilepticus
14.  Long-Term Survival and Outcome in Children Admitted to Kilifi District Hospital with Convulsive Status Epilepticus 
Objectives. The incidence of convulsive status epilepticus (CSE) is high in Africa but the long-term outcome is unknown. We examined the neurocognitive outcome and survival of children treated for CSE in a Kenyan hospital 3 to 4 years after discharge. Methods. The frequency and nature of neurological deficits among this group of children were determined and compared to a control group. The children were screened with the Ten Questions Questionnaire for neurodevelopmental impairment if alive and those that screened positive were invited for further assessment to determine the pattern and extent of their impairment. A verbal autopsy was performed to determine the cause of death in those that died. Results. In the 119 cases followed-up, 9 (8%) died after discharge, with the majority having seizures during their fatal illness. The 110 survivors (median age 5 years) had significantly more neurological impairments on the screening compared to 282 controls (34/110 (30.9%) versus 11/282 (3.9%), OR = 11.0, 95% CI 5.3–22.8). Fifteen percent of the cases had active epilepsy. Conclusions. This study demonstrates the considerable burden of CSE in African children. Strategies to manage children with CSE that are acceptable to the community need to be explored to improve the longer-term outcome.
doi:10.1155/2014/643747
PMCID: PMC3928879  PMID: 24627807
15.  Prospective study of new-onset seizures presenting as status epilepticus in childhood 
Neurology  2010;74(8):636-642.
Objective:
To characterize children with new-onset seizures presenting as status epilepticus at a tertiary care children's hospital.
Methods:
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.
Results:
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.
Conclusions:
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.
GLOSSARY
= convulsive status epilepticus;
= head CT;
= nonconvulsive status epilepticus;
= status epilepticus.
doi:10.1212/WNL.0b013e3181d0cca2
PMCID: PMC2830921  PMID: 20089940
16.  The pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus 
The Journal of Pediatrics  2011;160(4):667-672.e2.
Objective[mh2]
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.
Study design
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jpeds.2011.09.048
PMCID: PMC3274567  PMID: 22050870
17.  Status epilepticus. Current concepts and management. 
Canadian Family Physician  2000;46:1817-1823.
OBJECTIVE: To inform primary care physicians about current issues around generalized convulsive status epilepticus (GCSE) emphasizing definition, pathophysiology, treatment, and prognosis. QUALITY OF EVIDENCE: MEDLINE (1994 to 1999) provided 479 references using the MeSH terms "status epilepticus" and "treatment." From these we selected 30 English-language articles covering clinical aspects, treatment, and animal research. Key source documents from previous years and information from modern textbooks and recent symposia were also included. MAIN MESSAGE: Generalized convulsive status epilepticus continues to be a medical emergency with high morbidity and mortality. It must be managed promptly and effectively. The operational definition of GCSE is a seizure that lasts longer than 5 minutes or two or more seizures between which patients do not recover. Main differential diagnosis is nonepileptic status. Intravenous therapy with combined lorazepam and phenytoin is the initial treatment of choice. Other preferred medications are diazepam, midazolam, and propofol. Some of these medications should be considered before arrival at hospital. Prognosis of GCSE is determined by underlying cause, delay in adequate treatment, and comorbidity. Patients with GCSE lasting longer than 30 minutes require intensive care and electroencephalogram monitoring. CONCLUSION: Intravenous lorazepam and phenytoin are currently the most effective drugs for initial management of GCSE. Timely administration of antiepileptic medication can prevent development of GCSE in some patients with known epilepsy. Main differential diagnosis is nonepileptic status.
PMCID: PMC2145029  PMID: 11013800
18.  Non-convulsive status epilepticus. 
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.
PMCID: PMC1778178  PMID: 3813634
19.  Clinical and neurophysiological features of active convulsive epilepsy in rural Kenya: a population based study 
Epilepsia  2010;51(12):2370-2376.
Purpose
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.
Methods
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.
Results
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).
Discussion
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.
doi:10.1111/j.1528-1167.2010.02653.x
PMCID: PMC3188844  PMID: 20608962
epilepsy; convulsions; partial seizures; electroencephalogram; status epilepticus; sub-Saharan Africa
20.  Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures 
Objective
Intravenous (IV) levetiracetam (LEV) is approved for use in patients older than 16 years and may be useful in critically ill children, although there is little data available regarding pharmacokinetics. We aim to investigate the safety, an appropriate dosing, and efficacy of IV LEV in critically ill children.
Design
We describe a cohort of critically ill children who received IV LEV for status epilepticus, including refractory or nonconvulsive status, or acute repetitive seizures.
Results
There were no acute adverse effects noted. Children had temporary cessation of ongoing refractory status epilepticus, termination of ongoing nonconvulsive status epilepticus, cessation of acute repetitive seizures, or reduction in epileptiform discharges with clinical correlate.
Conclusions
IV LEV was effective in terminating status epilepticus or acute repetitive seizures and well tolerated in critically ill children. Further study is needed to elucidate the role of IV LEV in critically ill children.
doi:10.1097/PCC.0b013e3181a0e1cf
PMCID: PMC2946960  PMID: 19325512
levetiracetam; status epilepticus; seizure; pediatric
21.  Prolonged febrile seizures cause reversible reductions in white matter integrity☆ 
NeuroImage : Clinical  2013;3:515-521.
Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen.
33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) between patients and controls on a voxel-wise basis within the white matter skeleton.
Widespread reductions in FA along multiple white matter tracts were found at 1 and 6 months post-PFS, but these had resolved at 12 months. At one month post-PFS the main changes seen were reductions in AD but at 6 months these had predominantly changed to increases in RD.
These widespread white matter changes have not previously been noted following PFS. There are many possible explanations, but one plausible hypothesis is that this represents a temporary halting of normal white matter development caused by the seizure, that then resumes and normalises in the majority of children.
Highlights
•Widespread reductions in FA occur in children after prolonged febrile seizures.•These reductions persist up to 6 months post-PFS but resolve by 1 year.•This may represent a seizure-related disruption of white matter development.
doi:10.1016/j.nicl.2013.10.010
PMCID: PMC3830064  PMID: 24273734
Diffusion tensor imaging; Epilepsy; Febrile status epilepticus; TBSS
22.  Status epilepticus: Our experience in a tertiary care centre in Northwestern India 
Introduction:
Status epilepticus (SE) is a medical emergency. Aim of this study was to examine the etiology and outcome of adult patients in status epilepticus presenting to our center.
Patients and Methods:
A prospective study was conducted from January 2009 to December 2010. Newly diagnosed patients as well as known case of seizure disorder presenting with status epilepticus were included. Detailed history, clinical examination, baseline investigation, neuroimaging electroencephalogram findings were recorded. Patients were treated using a standard protocol and were followed-up for 2 weeks after discharge. Quantification of precipitating factors was done using proportion, mean and standard deviation.
Results:
80 consecutive patients were studied. Mean age was 38.43 ± 16.56 years (range 13 to 78 years). Male to female ratio was 4:1. 57.5% were known cases of seizure disorders. Generalized tonic-clonic seizure was commonest presentation in 91.30%. Majority (97.5%) had convulsive SE. Poor drug compliance was found to be the commonest precipitant (50% patients), followed by central nervous system infection (20% patients. Alcohol intake contributed in 12.5% cases, whereas, precipitating factor couldn't be traced in 7.5% patients'. In 55% patients, SE was controlled with no recurrence or complication and in 25% there was recurrence after control of SE. 15% patients ended up with persistent sequel (cognitive and psychosomatic dysfunction, neurological deficit etc.) lasting for 2 weeks or more. The mortality was 5%.
Conclusion:
Poor compliance with drugs (in established cases of seizure disorders) and central nervous systems infections/structural lesions (in new onset cases) were commonest causes of SE in our study group. Conventional first line antiepileptics were able to control seizures in only 55% patients.
doi:10.4103/0974-2700.125632
PMCID: PMC3912660  PMID: 24550623
Antiepileptics; emergency presentation; neurological emergency; seizures; status epilepticus
23.  Chronic Cellular Hyperexcitability in Elderly Epileptic Rats with Spontaneous Seizures Induced by Kainic Acid Status Epilepticus while Young Adults 
Aging and Disease  2011;2(4):332-338.
Emerging data indicate that age-related brain changes alter seizure susceptibility, seizure-associated neurodegeneration, and responsiveness to AEDs. The present study assessed long-term animal survival in the Kainic Acid (KA) model along with in-vivo spontaneous seizure frequency, cellular hyperexcitability in CA1 in-vitro and in-vivo in subiculum, and responsiveness of in-vitro CA1 hyperexcitability to topiramate. Sprague-Dawley male rats were given KA to induce convulsive status epilepticus (KA-SE) at 2–3 months of age. The one-month mortality after KA-SE was 27%. One-month survivor rats had 37% sudden unexplained late mortality after KA-SE as compared to none in saline controls during their second year of life. In-vivo seizure frequency was examined prior to terminal experiments. The diurnal average seizure frequency in the KA-SE group at age 2 years was 1.06 ± 0.24 seizures/hour while no seizures were observed in the saline age-matched controls (p<0.001). In-vitro recordings of CA1 pyramidal neurons revealed that depolarizing current injection from −60 mV evoked an increased number of action potentials in the aged KA-SE group compared to controls (p<0.002). Topiramate exhibited dose-dependent inhibition of action potential firing evoked by current injections into CA1 pyramidal neurons of KA-SE rats. In subiculum, KA-SE rats had frequent interictal spikes associated with high frequency oscillations while only rare spontaneous EPSPs were recorded in saline controls. Our experiments revealed that the hippocampal formation of aged epileptic rats shares features of hyperexcitability previously described in young adult epileptic rats using the KA model.
PMCID: PMC3295074  PMID: 22396885
Topiramate; Aged; Epilepsy; Bursting; Hippocampal slice; SUDEP
24.  Two Patients Diagnosed with Juvenile Myoclonic Epilepsy by First-Ever Status Epilepticus in Adult Life 
Journal of Epilepsy Research  2011;1(1):32-34.
Juvenile myoclonic epilepsy (JME) is an idiopathic, age-related generalized epileptic syndrome. Status epilepticus (SE) in JME is very rare, and little is known about its etiology. We report 2 cases of adult patients, retrospectively diagnosed as JME by non convulsive status epilepticus which occurred for the first time. One patient was a 52-year-old woman who was presented with confusion and brief generalized tonic-clonic seizure (GTCS) for the first time. The other patient, a 39 year-old woman, visited the ER with transient LOC following confused mental state. Electroencephalograms of both patients repetitively showed generalized polyspikes and slow waves which were disappeared after IV injection of lorazepam. With careful history taking, both of them the patients were diagnosed as JME, and the seizures stopped just after sodium valproate medication. NCSE in patients with JME is rare but detailed history taking and suspicion of the disorder is helpful for diagnosis.
doi:10.14581/jer.11007
PMCID: PMC3952312  PMID: 24649443
Juvenile myoclonic epilepsy; Status epilepticus; Epilepsy
25.  Serum prolactin response to metoclopramide during status epilepticus. 
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.
PMCID: PMC489205  PMID: 1527538

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