Epilepsy Research (2014) 108, 1609—1617
journal homepage: www.elsevier.com/locate/epilepsyres
Determinants and predictors of outcome in super refractory status epilepticus—–A developing country perspective Sita Jayalakshmi a,∗, Devashish Ruikar a, SudhindraVooturi a, Suvarna Alladi b,1, Sambit Sahu c,2, Subhash Kaul b,1, Surath Mohandas a a
Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 03, Andhra Pradesh, India b Department of Neurology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India c Department of Critical Care, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 03, Andhra Pradesh, India Received 28 May 2014; received in revised form 6 August 2014; accepted 21 August 2014 Available online 30 August 2014
KEYWORDS Encephalitis; Super refractory status epilepticus; Acidosis; Mortality; Status epilepticus
∗ 1 2
Summary Importance: Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. Objective: We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. Methods: In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. Main outcome measure: The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Results: Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p < 0.01), elderly (21.7%; p < 0.003), and in incident SE (82·1%, p = 0.05). Encephalitis was the commonest etiology
Corresponding author. Tel.: +91 9848019036; fax: +91 40 27840980. E-mail addresses: sita [email protected], [email protected] (S. Jayalakshmi). +91 40 23489143. +91 40 44185000.
http://dx.doi.org/10.1016/j.eplepsyres.2014.08.010 0920-1211/© 2014 Elsevier B.V. All rights reserved.
1610
S. Jayalakshmi et al. in RSE (30.9%, p = 0.015), SRSE (66.7%, p < 0.001) than NRSE (12.3%). Encephalitis (ˇ = 8.250 (1.8—37.82); p = 0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35·7%), both significantly (p < 0.001) higher than NRSE (6·7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p = 0.001). Acidosis predicted mortality in the entire cohort (ˇ = 7.313 (1.6—32.58); p = 0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p = 0.055), and NRSE (33.3% vs. 79.1%; p < 0.0001). Conclusions and relevance: SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with SRSE survived and one third had good outcome. Therefore one should continue the care inspite of weeks of SE. © 2014 Elsevier B.V. All rights reserved.
Introduction Status epilepticus (SE) is a life threatening neurological emergency associated with significant morbidity, and mortality. The average incidence of SE is about 20 per 100,000 (Coeytaux et al., 2000; Jallon et al., 1999; Knake et al., 2001) with peak incidences reported during first year of life, and after the age of 60 (Chin et al., 2006). Etiology of SE varies with age, the most common cause in children being central nervous system (CNS) infections, whereas in adults, it includes cerebrovascular accident, metabolic encephalopathy, and hypoxia (Garzon et al., 2003; Mayer et al., 2002). Acute symptomatic etiology particularly presumed encephalitis is associated with poor prognosis in patients with SE (Holtkamp et al., 2005b). The short term mortality in SE is about 20% (Coeytaux et al., 2000; Jallon et al., 1999; Wu et al., 2002) depending upon the age, duration of SE, and etiology (Hauser, 1990; Wu et al., 2002). These observations may be more relevant to tropical country like India where data about incidence rate of acute encephalitis syndrome, especially its role in prolonged RSE is limited. Few recent studies have however suggested that the landscape of encephalitis in India is changing where surveillance studies have increasingly reported non-Japanese encephalitis virus (JEV) aetiologies and emphasized on strategies beyond vector control and JEV vaccination (Joshi et al., 2012) thus making it different from its immediate neighbor countries (Potharaju, 2012). First and second line anticonvulsants (benzodiazepines, and phenytoin) do not terminate SE in about 40%; (Treiman et al., 1998) SE resistant to one first line, and one second line anti epileptic drug (AED) is coined as refractory status epilepticus (RSE) (Mayer et al., 2002). Moreover SE tends to get resilient to treatment with anti-convulsants, and over time sedation or inducing coma with appropriate drugs is suggested (Lowenstein and Alldredge, 1998). RSE, if continues or recurs 24 h after administration of initial anesthesia therapy has recently been termed as super refractory status epilepticus (SRSE) (Shorvon, 2011). Super RSE persists for weeks with poor prognosis (Towne et al., 1994), and is a major concern for the patient’s family, and the treating physician. Prolonged mechanical ventilation, etiology, and comorbidities are established predictors of in-hospital mortality in patients with generalized convulsive SE (Koubeissi and
Alshekhlee, 2007). Mortality in RSE patients has also been attributed to acute CNS disorders like presumed encephalitis (Hocker et al., 2013; Holtkamp, 2007), older age (Claassen et al., 2002; Logroscino et al., 1997; Waterhouse et al., 1999), and etiology (Claassen et al., 2002; Logroscino et al., 1997; Lowenstein and Alldredge, 1993; Towne et al., 1994; Waterhouse et al., 1999). Outcome may be particularly poor in patients with SRSE, characterized by relapse of SE despite administration of anesthetics (Krishnamurthy and Drislane, 1996) and a prolonged in-hospital stay (Towne et al., 1994). Holtkamp et al. (2005a) categorized adult SRSE patients (n = 7) as ‘‘malignant’’ RSE patients and reported that these patients were typically aged young, suffered from presumed encephalitis and had poorer outcome at discharge than RSE patients. Sahin et al. (2001) in a group of 22 children of ‘‘severe’’ RSE reported that mortality is related to etiology and is higher in younger children. Most of the available literature on SRSE is either restricted to a single age group or from developed countries. Understanding the clinical spectrum of SRSE across age groups may help formulate tailor made treatment strategies. In the current study from a developing country, we evaluated the determinants of SRSE, and assessed the clinical characteristics and outcome (immediate and at 6 months) in patients with SRSE in comparison to NRSE, RSE patients and also across three age groups.
Materials and methods This open cohort was part of a larger epilepsy registry. Analysis of data of patients with convulsive SE admitted between May 2005, and October 2013 in the neurointensive care unit (NICU) of Krishna institute of Medical Sciences, and Nizam’s institute of Medical Sciences, two tertiary care referral centers at Hyderabad in South India was performed. Patients with complex partial SE, absence SE, simple partial SE, myoclonic SE, psychogenic SE, and those with non-convulsive SE were excluded for data analysis. The information about age, gender, duration of SE, associated co-morbidities, past history of epilepsy and/or SE, duration of ventilator care, associated complications—–fever, severe sepsis, pneumonia, acute kidney injury, hepatic failure, acidosis, significant cardiac disturbances, and duration of NICU stay was obtained. Etiology of SE was classified
Determinants and predictors of outcome in super refractory status epilepticus—–A developing country perspective as acute symptomatic, remote symptomatic, those with pre-existing epilepsy, and idiopathic (cause undetermined) (1993). Acute symptomatic group included patients with CNS inflammatory disease (presumed encephalitis, tuberculosis, and neurocysticercosis), acute cerebrovascular CNS disease (ischemic/hemorrhagic stroke, cortical sinus venous thrombosis), and those with metabolic etiologies. The study was approved after review by the Institutional Ethics Committee.
Definitions Status Epilepticus was defined as seizures lasting for more than 5 min or recurrent epileptic activity over a period of more than 5 min without regain of pre-existing level of consciousness (Lowenstein et al., 1999). RSE was defined as SE resistant to one first line, and one second line AED, requiring general anaesthesia (GA) (Mayer et al., 2002). SRSE was defined as SE that continues 24 h or more after the onset of anaesthesia, including those cases in which the SE recurs on the reduction or withdrawal of anaesthesia (Shorvon, 2011; Shorvon and Ferlisi, 2012). If SE recurred days after withdrawal of anaesthetic drugs, and warranted re-administration of similar drugs, the length of the NICU stay included the seizure free days too. Presumed encephalitis: Encephalopathy (depressed or altered level of consciousness) lasting >24 h with fever, and seizures along with one or more than one of the following symptoms: focal neurological deficits, cerebrospinalfluid (CSF) mononuclear pleocytosis, electroencephalogram (EEG) or neuroimaging findings consistent with presumed encephalitis, after excluding systemic infective causes (Granerod et al., 2010). All patients had baseline, and follow up CT/MRI brain. CSF for anti N-methyl-D-aspartate receptor (NMDAR) antibodies, antibodies against voltage-gated potassium channels (VGKC), and antiglutamic acid decarboxylase (GAD) antibodies was done in 9 patients with SRSE.
Treatment All the patients were treated according to established guidelines (Shorvon, 2011). The initial treatment during early stages included 4 mg IV bolus dose of benzodiazepines (lorazepam or midazolam). When the SE progressed to established stage, intravenous (IV) AEDs (phenytoin, phenobarbitone, sodium valproate or levetiracetam alone or in combination) were administered. The most commonly used first IV AED was phenytoin sodium (in 85 patients) followed by Levetiracetam (16 patients) and valproic acid (4 patients). The commonest AED given in adjunct to phenytoin was phenobarbitone (29 patients) and levetiracetam (11 patients). Eighteen patients were administered third AED as adjunctive therapy. Intravenous Lacosamide and oral Topiramate were given in fourteen patients with RSE. The commonest IV anaesthesia drug used was midazolam (42 patients) whereas thiopental was used in 28 and propofol in three patients. Eight patients received ketamine. Steroids (49 patients), intravenous immunoglobulins (10 patients), and ketogenic diet (five children) were used in selected patients with RSE. Continuous EEG monitoring was performed in 98 patients (including all patients with RSE, and
1611
SRSE). Appropriate management of the underlying medical/neurological condition was done.
Complications and outcome Severe sepsis, acute kidney injury and acute hepatic failure were defined according to established guidelines (Levy et al., 2003). The immediate outcome in hospital was classified as death or discharge from the hospital. The outcome at 6 months was graded according to the Glasgow outcome scale (GOS) (Jennett and Bond, 1975) that grades patients’ functional status into the following five categories: 1-death, 2-persistent vegetative state, 3-severe disability, 4-moderate disability and 5-low disability. Patients with moderate and low disability were categorized as good outcome group and the rest as poor outcome group.
Statistical analysis After testing for the normal distribution of the data, the study population was divided into groups based on type of SE and age. Differences between the groups for continuous variables were analyzed using independent student t-test, accounting for variance amongst group using Levene’s test for equality of variance. Categorical variables were analyzed using chi-square test. A p < 0.05 was considered significant. Variables that were significantly different between the groups were included in logistic regression model to help evaluate progression of SE to SRSE and predictors of mortality. Mortality between the groups for patients with presumed encephalitis as etiology was compared using Kaplan Meir survival analysis. Statistical Package for Social Sciences (SPSS, ver. 17.0, IBM computers, New York, USA) was used for all statistical analysis.
Results Demographic and clinical characteristics In this open cohort of 177 patients, 105 (59.3%) represented non-refractory SE (NRSE); 72 had documented RSE (40.7%) of which 30 (16.9% of 177) were further classified as SRSE. The mean age of the entire cohort was 31.6 ± 19.2 years; 58.8% were men. The demographic and measured clinical variables across the three SE groups are summarized in Table 1. SRSE was significantly more common in children (39%vs. 7.9%; p < 0.0001), and elderly (21.7% vs. 7.9%; p = 0.0334) than adults (Table 2). Incident SE was noted in 64.4% (114) of the entire cohort. Incident SE was more common in SRSE than NRSE (82.1% vs. 59%; p = 0.05). However no difference for incident SE was noted across age groups.
Etiology Acute symptomatic etiology accounted for 112 cases (63·2%), more prevalent in SRSE than NRSE (80.0% vs. 56.2%, p = 0.019) (Table 1). It was the commonest etiology across all the three age groups (Table 2). Amongst the acute symptomatic group, presumed encephalitis was more common in SRSE (66.7% vs. 12.3%, p < 0.001), and RSE (30.9% vs.
1612 Table 1
S. Jayalakshmi et al. Comparison of study variables between NRSE, RSE, and SRSE.
Variable
NRSE (n: 105)
RSE (n: 42)
SRSE (n: 30)
Age Children (
journal homepage: www.elsevier.com/locate/epilepsyres
Determinants and predictors of outcome in super refractory status epilepticus—–A developing country perspective Sita Jayalakshmi a,∗, Devashish Ruikar a, SudhindraVooturi a, Suvarna Alladi b,1, Sambit Sahu c,2, Subhash Kaul b,1, Surath Mohandas a a
Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 03, Andhra Pradesh, India b Department of Neurology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India c Department of Critical Care, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 03, Andhra Pradesh, India Received 28 May 2014; received in revised form 6 August 2014; accepted 21 August 2014 Available online 30 August 2014
KEYWORDS Encephalitis; Super refractory status epilepticus; Acidosis; Mortality; Status epilepticus
∗ 1 2
Summary Importance: Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. Objective: We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. Methods: In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. Main outcome measure: The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Results: Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p < 0.01), elderly (21.7%; p < 0.003), and in incident SE (82·1%, p = 0.05). Encephalitis was the commonest etiology
Corresponding author. Tel.: +91 9848019036; fax: +91 40 27840980. E-mail addresses: sita [email protected], [email protected] (S. Jayalakshmi). +91 40 23489143. +91 40 44185000.
http://dx.doi.org/10.1016/j.eplepsyres.2014.08.010 0920-1211/© 2014 Elsevier B.V. All rights reserved.
1610
S. Jayalakshmi et al. in RSE (30.9%, p = 0.015), SRSE (66.7%, p < 0.001) than NRSE (12.3%). Encephalitis (ˇ = 8.250 (1.8—37.82); p = 0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35·7%), both significantly (p < 0.001) higher than NRSE (6·7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p = 0.001). Acidosis predicted mortality in the entire cohort (ˇ = 7.313 (1.6—32.58); p = 0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p = 0.055), and NRSE (33.3% vs. 79.1%; p < 0.0001). Conclusions and relevance: SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with SRSE survived and one third had good outcome. Therefore one should continue the care inspite of weeks of SE. © 2014 Elsevier B.V. All rights reserved.
Introduction Status epilepticus (SE) is a life threatening neurological emergency associated with significant morbidity, and mortality. The average incidence of SE is about 20 per 100,000 (Coeytaux et al., 2000; Jallon et al., 1999; Knake et al., 2001) with peak incidences reported during first year of life, and after the age of 60 (Chin et al., 2006). Etiology of SE varies with age, the most common cause in children being central nervous system (CNS) infections, whereas in adults, it includes cerebrovascular accident, metabolic encephalopathy, and hypoxia (Garzon et al., 2003; Mayer et al., 2002). Acute symptomatic etiology particularly presumed encephalitis is associated with poor prognosis in patients with SE (Holtkamp et al., 2005b). The short term mortality in SE is about 20% (Coeytaux et al., 2000; Jallon et al., 1999; Wu et al., 2002) depending upon the age, duration of SE, and etiology (Hauser, 1990; Wu et al., 2002). These observations may be more relevant to tropical country like India where data about incidence rate of acute encephalitis syndrome, especially its role in prolonged RSE is limited. Few recent studies have however suggested that the landscape of encephalitis in India is changing where surveillance studies have increasingly reported non-Japanese encephalitis virus (JEV) aetiologies and emphasized on strategies beyond vector control and JEV vaccination (Joshi et al., 2012) thus making it different from its immediate neighbor countries (Potharaju, 2012). First and second line anticonvulsants (benzodiazepines, and phenytoin) do not terminate SE in about 40%; (Treiman et al., 1998) SE resistant to one first line, and one second line anti epileptic drug (AED) is coined as refractory status epilepticus (RSE) (Mayer et al., 2002). Moreover SE tends to get resilient to treatment with anti-convulsants, and over time sedation or inducing coma with appropriate drugs is suggested (Lowenstein and Alldredge, 1998). RSE, if continues or recurs 24 h after administration of initial anesthesia therapy has recently been termed as super refractory status epilepticus (SRSE) (Shorvon, 2011). Super RSE persists for weeks with poor prognosis (Towne et al., 1994), and is a major concern for the patient’s family, and the treating physician. Prolonged mechanical ventilation, etiology, and comorbidities are established predictors of in-hospital mortality in patients with generalized convulsive SE (Koubeissi and
Alshekhlee, 2007). Mortality in RSE patients has also been attributed to acute CNS disorders like presumed encephalitis (Hocker et al., 2013; Holtkamp, 2007), older age (Claassen et al., 2002; Logroscino et al., 1997; Waterhouse et al., 1999), and etiology (Claassen et al., 2002; Logroscino et al., 1997; Lowenstein and Alldredge, 1993; Towne et al., 1994; Waterhouse et al., 1999). Outcome may be particularly poor in patients with SRSE, characterized by relapse of SE despite administration of anesthetics (Krishnamurthy and Drislane, 1996) and a prolonged in-hospital stay (Towne et al., 1994). Holtkamp et al. (2005a) categorized adult SRSE patients (n = 7) as ‘‘malignant’’ RSE patients and reported that these patients were typically aged young, suffered from presumed encephalitis and had poorer outcome at discharge than RSE patients. Sahin et al. (2001) in a group of 22 children of ‘‘severe’’ RSE reported that mortality is related to etiology and is higher in younger children. Most of the available literature on SRSE is either restricted to a single age group or from developed countries. Understanding the clinical spectrum of SRSE across age groups may help formulate tailor made treatment strategies. In the current study from a developing country, we evaluated the determinants of SRSE, and assessed the clinical characteristics and outcome (immediate and at 6 months) in patients with SRSE in comparison to NRSE, RSE patients and also across three age groups.
Materials and methods This open cohort was part of a larger epilepsy registry. Analysis of data of patients with convulsive SE admitted between May 2005, and October 2013 in the neurointensive care unit (NICU) of Krishna institute of Medical Sciences, and Nizam’s institute of Medical Sciences, two tertiary care referral centers at Hyderabad in South India was performed. Patients with complex partial SE, absence SE, simple partial SE, myoclonic SE, psychogenic SE, and those with non-convulsive SE were excluded for data analysis. The information about age, gender, duration of SE, associated co-morbidities, past history of epilepsy and/or SE, duration of ventilator care, associated complications—–fever, severe sepsis, pneumonia, acute kidney injury, hepatic failure, acidosis, significant cardiac disturbances, and duration of NICU stay was obtained. Etiology of SE was classified
Determinants and predictors of outcome in super refractory status epilepticus—–A developing country perspective as acute symptomatic, remote symptomatic, those with pre-existing epilepsy, and idiopathic (cause undetermined) (1993). Acute symptomatic group included patients with CNS inflammatory disease (presumed encephalitis, tuberculosis, and neurocysticercosis), acute cerebrovascular CNS disease (ischemic/hemorrhagic stroke, cortical sinus venous thrombosis), and those with metabolic etiologies. The study was approved after review by the Institutional Ethics Committee.
Definitions Status Epilepticus was defined as seizures lasting for more than 5 min or recurrent epileptic activity over a period of more than 5 min without regain of pre-existing level of consciousness (Lowenstein et al., 1999). RSE was defined as SE resistant to one first line, and one second line AED, requiring general anaesthesia (GA) (Mayer et al., 2002). SRSE was defined as SE that continues 24 h or more after the onset of anaesthesia, including those cases in which the SE recurs on the reduction or withdrawal of anaesthesia (Shorvon, 2011; Shorvon and Ferlisi, 2012). If SE recurred days after withdrawal of anaesthetic drugs, and warranted re-administration of similar drugs, the length of the NICU stay included the seizure free days too. Presumed encephalitis: Encephalopathy (depressed or altered level of consciousness) lasting >24 h with fever, and seizures along with one or more than one of the following symptoms: focal neurological deficits, cerebrospinalfluid (CSF) mononuclear pleocytosis, electroencephalogram (EEG) or neuroimaging findings consistent with presumed encephalitis, after excluding systemic infective causes (Granerod et al., 2010). All patients had baseline, and follow up CT/MRI brain. CSF for anti N-methyl-D-aspartate receptor (NMDAR) antibodies, antibodies against voltage-gated potassium channels (VGKC), and antiglutamic acid decarboxylase (GAD) antibodies was done in 9 patients with SRSE.
Treatment All the patients were treated according to established guidelines (Shorvon, 2011). The initial treatment during early stages included 4 mg IV bolus dose of benzodiazepines (lorazepam or midazolam). When the SE progressed to established stage, intravenous (IV) AEDs (phenytoin, phenobarbitone, sodium valproate or levetiracetam alone or in combination) were administered. The most commonly used first IV AED was phenytoin sodium (in 85 patients) followed by Levetiracetam (16 patients) and valproic acid (4 patients). The commonest AED given in adjunct to phenytoin was phenobarbitone (29 patients) and levetiracetam (11 patients). Eighteen patients were administered third AED as adjunctive therapy. Intravenous Lacosamide and oral Topiramate were given in fourteen patients with RSE. The commonest IV anaesthesia drug used was midazolam (42 patients) whereas thiopental was used in 28 and propofol in three patients. Eight patients received ketamine. Steroids (49 patients), intravenous immunoglobulins (10 patients), and ketogenic diet (five children) were used in selected patients with RSE. Continuous EEG monitoring was performed in 98 patients (including all patients with RSE, and
1611
SRSE). Appropriate management of the underlying medical/neurological condition was done.
Complications and outcome Severe sepsis, acute kidney injury and acute hepatic failure were defined according to established guidelines (Levy et al., 2003). The immediate outcome in hospital was classified as death or discharge from the hospital. The outcome at 6 months was graded according to the Glasgow outcome scale (GOS) (Jennett and Bond, 1975) that grades patients’ functional status into the following five categories: 1-death, 2-persistent vegetative state, 3-severe disability, 4-moderate disability and 5-low disability. Patients with moderate and low disability were categorized as good outcome group and the rest as poor outcome group.
Statistical analysis After testing for the normal distribution of the data, the study population was divided into groups based on type of SE and age. Differences between the groups for continuous variables were analyzed using independent student t-test, accounting for variance amongst group using Levene’s test for equality of variance. Categorical variables were analyzed using chi-square test. A p < 0.05 was considered significant. Variables that were significantly different between the groups were included in logistic regression model to help evaluate progression of SE to SRSE and predictors of mortality. Mortality between the groups for patients with presumed encephalitis as etiology was compared using Kaplan Meir survival analysis. Statistical Package for Social Sciences (SPSS, ver. 17.0, IBM computers, New York, USA) was used for all statistical analysis.
Results Demographic and clinical characteristics In this open cohort of 177 patients, 105 (59.3%) represented non-refractory SE (NRSE); 72 had documented RSE (40.7%) of which 30 (16.9% of 177) were further classified as SRSE. The mean age of the entire cohort was 31.6 ± 19.2 years; 58.8% were men. The demographic and measured clinical variables across the three SE groups are summarized in Table 1. SRSE was significantly more common in children (39%vs. 7.9%; p < 0.0001), and elderly (21.7% vs. 7.9%; p = 0.0334) than adults (Table 2). Incident SE was noted in 64.4% (114) of the entire cohort. Incident SE was more common in SRSE than NRSE (82.1% vs. 59%; p = 0.05). However no difference for incident SE was noted across age groups.
Etiology Acute symptomatic etiology accounted for 112 cases (63·2%), more prevalent in SRSE than NRSE (80.0% vs. 56.2%, p = 0.019) (Table 1). It was the commonest etiology across all the three age groups (Table 2). Amongst the acute symptomatic group, presumed encephalitis was more common in SRSE (66.7% vs. 12.3%, p < 0.001), and RSE (30.9% vs.
1612 Table 1
S. Jayalakshmi et al. Comparison of study variables between NRSE, RSE, and SRSE.
Variable
NRSE (n: 105)
RSE (n: 42)
SRSE (n: 30)
Age Children (
