Status epilepticus (SE) is a common neurological emergency. It has short-term mortality that ranges from 0.9 to 3.6% in children. The most vulnerable structure to seizures is the hippocampus, which is involved in learning and memory. Other structures have been demonstrated to show necrosis following events of epileptic attacks such as the amygdala, dorsomedial thalamic nucleus, medial layers of the neocortex, cerebellum, the piriforme, and entorhinal cortices, so SE has a destructive effect on the cognitive, motor, or sensory functions(1–4). SE outcome is mainly determined by any delays in treatment, the degree of refractoriness of the seizures, the underlying etiology, and the response to treatment. Determining the factors that can predict the outcome of patients with SE is very significant as this may be useful and essential for deciding on any further treatment, which can affect the prognosis directly( 13,14,15)
Age is a strong indicator of outcome in SE. In children younger than 2 years, febrile and acute symptomatic etiologies are most common, whereas cryptogenic and remote symptomatic etiologies are more common in older children. SE in young children occurs primarily in children who are neurologically normal and with no history of unprovoked seizures. In some research the mortality due to SE increases in children younger than 1 year old this could be due to the that the brain is in a period of fast development (16). In our study it was noticed that age didn’t play a role in the prognosis of SE this could be due to that most of our patients younger than 2 years old had SE due to acute symptomatic as meningoencephalitis and febrile SE and unknown origin. The effect of age could be due to two causes the first one is that the first years are very important regarding brain development so any insult could end up with a poor prognosis and the second one is the etiology of SE differ with age.
Gender could also affect the prognosis of SE. According to a study conducted on adult patients to assess the role of Gender in SE The hospital-based prevalence of status epilepticus appeared to be higher for men than women. Hospital stay for men with status epilepticus was shorter compared to females, which indicates that the severity of status epilepticus is higher among females requiring hospital longer treatment(17). In our study, it was noticed that the mean age group of our study is five years old and that gender didn't play a role in the prognosis of SE this may be due to the hormone system doesn't work so differently in young males and females as it does in adult male and female. That is why possibly the age in our study didn't affect the prognosis of SE. At the same time, The gender difference may be multifactorial but it is usually attributed to the greater exposure of males to risk factors for remote symptomatic epilepsy and acute symptomatic seizures, particularly head injury, stroke, and CNS infection. Which are significantly more common in male patients Future research needs to focus on this gender health Ethnicity is also a factor that can play a major role in the prognosis. There is a higher incidence of SE and lower mortality among blacks. This could be related to the underlying illness, access to medical care, compliance, or other intrinsic biologic factors. In our study, all the included patients were Asian so such a comparison couldn't be done(18)
An impaired level of consciousness at SE onset is independently associated with mortality. In a recent retrospective population-based study of adult patients with SE in Salzburg, impaired consciousness was associated with high case fatality, 33%, as compared with 8.2% in awake patients. In the same study, case fatality was 2.8% in awake patients with prominent motor semiology versus 26.9% in somnolent, stuporous, or comatose patients. In nonconvulsive status epilepticus (NCSE) patients, case fatality was 0% in fully awake, 13.9% in awake with reduced cognition, 36.8% in somnolent, 46.2% in stuporous, and 42.9% in comatose patients ( 18,19).In our study, 47% of the patients were alert, confused somnolent in the good prognosis group and %4 in the poor prognosis group, while 53% of comatose and stuporous were in the good prognosis group compared to 96% in the poor prognosis group. This could be explained by the destruction that happens in the brain cell due to prolonged seizure, and the longer the status epilepticus continues, the more impossible hazardous is resulted due to increased energy metabolism, hyperperfusion, and cell swelling, and this destruction leads to impaired function of brain cells and thus to impaired consciousness Semiology could play a role in the prognosis of SE. According to a study generalized Myoclonic SE is associated with poor outcomes and high mortality, but the characteristics of myoclonus in the studies were inconsistent. We know from the STESS system that generalized seizure has a worse prognosis compared to focal ones. Our study match these results( 18,19)
It is difficult to know the exact duration of SE because the onset is frequently not observed. Overall, a longer duration of SE was associated with higher mortality. However, new onset refractory status epilepticus can be associated with significant recovery even after a prolonged duration of SE. In our study the duration of SE couldn't be obtained from the medical files but we followed a male patient aged 10 years old with SE in the intensive care unit( ICU) due to FIRES he had very prolonged durations and frequent SE in spite of fourth line treatment protocol of SE, he had no seizure-free periods and he died 9 months after admission into ICU due to complications
EEG findings were overall less important than the duration of SE and etiology as predictors of outcomes. The pattern of EEG is non-specific in SE in children. In a systematic review of adult patients with SE, periodic epileptiform discharges (PEDs) were found to be associated with poor outcomes. In an EEG study of 50 patients, PEDs were associated with higher mortality/vegetative state (44%) when compared with those without PEDs (19%). In a prospective study of 180 patients using at least 24 hours of continuous EEG recording, the authors found that the presence of a burst suppression pattern and postictal discharges followed by PEDs was associated with higher mortality. Normalization of the EEG after SE correlated with good outcomes (18,19). In our study, the patients with slowing EEG had a worse prognosis than patients with normal EEG or with spike or/and sharp waves. The PEDs happens mainly due to diffusion restriction in the cortical area which is commonly seen in SE. In a recently investigated small patient sample, diffusion-weighted MR images (DWI) restrictions were detected in approximately 50% of patients with SE. In an earlier patient series comprising 85 SE patients, only 11.6% presented with DWI restriction. In our study, 9,7% of the patients had diffusion restriction in apparent diffusion coefficient (ADC), despite that no patient had PEDs which could be due to that the earlier the imaging is acquired, the higher is the probability of uncovering these changes. Furthermore, the incidence of DWI restriction seemed to correlate with total seizure duration. Abnormal MRI findings are considered among the prognostic factors An ictal and early postictal changes have been described on MRI in SE. These changes can be limited to the area of epileptic activity or far from this region. Knowing these anomalies might be essential to avoid any confusion with other focal lesions such as brain tumors, stroke, or encephalitis. Local MRI findings in SE can be in form of restricted diffusion in the diffusion-weighted image ( DWI), hyperintensity T2 better seen in fluid-attenuated inversion recovery (FLAIR) images, of the focal structure swelling, hyperperfusion of cerebrum in magnetic resonance perfusion. These MRI images are mainly reversible but could also become permanent and irreversible in severe and prolonged SE. Huang et al. studied 15 patients’ MRIs with SE. These MRI abnormalities consist of decreased diffusion in DWI, decreased apparent diffusion coefficient (ADC), and increased signal in T2 usually accompanied by focal cerebral edema and increased vascularization( 20–25). In Our study 7(9.7%) patients had T2 hyperintensity increase and decreased ADC. Supposingly, a failure of the Na/K ATPase pump leads to cellular sodium and water influx resulting in cytotoxic edema. Other mechanisms may include the excessive release of exciting amino acids such as glutamate and increased membrane ion permeability. Other MRI abnormalities related to lesions as intracranial bleeding TSC lesions, lissencephaly, and structural abnormalities( 16–19). In our study, it was concluded that the presence of abnormal MRI-CT was in favor of poor outcomes in SE in children.
Metabolic imbalance plays a crucial role in the prognosis. A decrease of glucose and glycogen with parallel rises of lactate indicates a high rate of glycolysis, Seizures can result in profound elevations of serum lactate. In a study on adult patients with seizures conducted by Erduer et al. on the relation of high blood lactate, mortality, and bad prognosis, no relation could be established. In our study, we concluded the patients with poor prognosis mainly had a higher level of blood lactate yet the mean average blood lactate level is under 2 mmol/l which can be considered normal because the other studies when they classified high and low levels of lactate choose the cut off 2 mmol/l as an indicator of high level. The difference between conducted studies' results could due to many factors as the pediatric population and the time of getting blood samples. presence of other comorbidities like an infection which could violate the blood table. The most common reason for SE in outpatients was an infection, an unknown reason for febrile status, (26–27).
Biochemical Markers Neuronal damage biomarkers (neuron-specific enolase and tau proteins) Elevated neuron-specific enolase (NSE) levels can be indicative of neuronal injury. Tau protein Procalcitonin, C-reactive protein (CRP), Procalcitonin, albumin, uric acid, and cytokines as (interleukin-1B, interleukin-2, interleukin-6, and tumor necrosis factor-alpha) could reflect the degree of the injury in SE our study was retrospective one so most of these markers were not investigated (18).
Associated conditions can always complicate the course of the SE and it is considered an important prognostic factor Cardiac arrhythmia, cardiac damage because of catecholamine surge, respiratory failure, hypoventilation, hypoxia, aspiration pneumonia, pulmonary edema, fever, and leukocytosis are some of the common and serious complications seen in patients with status epilepticus so the presence of this complication can also affect the prognosis in SE. In our study no effect of low blood pressure and arrhythmia, or intubation on the poor prognosis although in our study there was a male patient aged 10 years old followed with FIRES and experienced low blood pressure arrhythmia intubation and multiple organ failure, he died 9 months after admission to the pediatric intensive care unit. he experienced süper refractor SE despite 3. line anesthetic agent IVIG, pulse methylprednisolone, anakinra ketogenic diet, cannabidiol, lacosamide, and lorazepam treatment. The co-morbidities as valvular heart disease, renal failure, liver disease, and autism can co-exist with SE in children.These comorbidities can affect the prognosis of SE. most of the studies researching the effect of comorbidities on the prognosis of SE are conducted in adult patients one of these studies Vincent Alvarez, et al. study in which they concluded comorbidities and the clinical presentation seem to affect the outcome of SE in a relatively marginal way. The comorbidities of the adult patients in this study were mainly cerebrovascular disease, Any tumor Chronic pulmonary disease Solid metastatic tumor Congestive heart disease Moderate/severe renal disease)Dementia, Myocardial infarction Peptic ulcer, Peripheral vascular disease, Hemiplegia liver disease, Diabetes Connective tissue disease Lymphoma Diabetes. The presence of comorbidities does not necessarily predict a poor outcome, this should not dissuade neurologists from treating patients with SE and comorbid conditions appropriately( 28,29). In our study, the presence of comorbid conditions was seen in 46 (61%) of the total number of patients and 26 (%96) of the patients with poor prognoses. According to our study co-morbidities play a crucial role in SE prognosis. And its presence was in favor of poor prognosis. Comorbidities are important regarding contraindications and side effects of antiepileptic drugs. In this regard, they may influence the outcome by influencing the utilization of specific treatments
STESS has been proven to be a good predictor of morbidity, mortality, and the urgent need for aggressive treatment. m- STESS or Status Epilepticus Pediatric Severity Score(STEPSS) has been tested in a study in India by Sidharth et al. One-hundred and forty children (mean age 5.8 years) were enrolled in this study. Seven children died and overall 15 children had an unfavorable outcome. The predictive accuracy of m-STESS( STEPSS) was at a cut-off of > 3: for unfavorable outcomes( 11). In Our study, this cut was > 2 for unfavorable outcomes and 4 for mortality. The difference of one point between the 2 studies could be due to the different groups of the patient in the two studies. In our study, the mean age of the patients is 5.3 years, the number of male patients to female ones was almost the same and the percentage of previous epilepsy is 53% which almost resembles Sidharth et al study’s variabilities except for the male/ female ration which looks higher in Sidharth et a. study. At the same time, the most three common SE in our study were meningoencephalitis (19%), Unknown febrile (12%) status (8% ), and genetic diseases 7%. while in Sidharth et al the most common etiologies were acute symptomatic which was present in 25.7%, followed by remote symptomatic which was present in 25% of patients and febrile status epilepticus was present in 18.6%. The percentage of different etiologies between the two studies might play a role in resulting in different cuts of value for unfavorable outcomes.
One of the other score systems to evaluate the prognosis of pediatric patients with convulsive SE is the PEDSS score which has high predictive accuracy for mortality and differentiates good from poor outcomes at the hospital and 3 months postdischarge. This score in the PEDSS system depends on Premorbid PCPCS, Abnormal background on EEG, and Drug refractoriness, Critically sick: the presence of intubation, shock, and multiple organ dysfunctions (MODS) in isolation or combination and semiology focal seizures is favorable but generalized ones not. So PEDSS is not a bedside simple score system as m- STESS( STEPSS). We should wait to evaluate the response to the treatment and whether there is organ failure during management. According to the study by Tiwari et al., the cut-off PEDSS scores for mortality and poor outcome at the hospital and 3 months post-discharge were ≥ 4, ≥3, and ≥ 3, respectively (12). In our study, the cut-off for poor prognosis was ≥ 3 at the hospital before discharge and 6 for mortality. Our results match the results of Tiwari et al. for unfavorable outcomes in the hospital but didn’t match with the mortality score this could because there is one only one patient died due to SE in our patient so this Score appears to be suitable to use to evaluate the prognosis of convulsive SE in the pediatric population. However, we couldn’t evaluate our patients after three months due to different reasons. One of the most important ones is that our study was retrospective unlike Tiwari et al which was a prospective one and one of the other reasons was the Covid pandemic so the post-three-month score could not be evaluated.in our study According to our study results o havings a high score of Premorbid PCPCS, slowing and abnormal background on EEG, and having generalized epilepsy could result in unfavorable outcomes in convulsive SE in children.
In conclusion, Generalized type of seizures and non-convulsive SE, slowing and abnormal ground in EEG, being stuporous or comatose, abnormal MRI-CT, higher PCPCS score, PEDSS ≥ 3, mSTESS ≥ 2, presence of comorbid condition were in favor of poor prognosis in SE in children.
Limitation of the study
Conducting a retrospective is considered a limitation of the study