| Abstract|| |
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.
Keywords: Antiepileptics, emergency presentation, neurological emergency, seizures, status epilepticus
|How to cite this article:|
Bhalla A, Das B, Som R, Prabhakar S, Kharbanda PS. Status epilepticus: Our experience in a tertiary care centre in Northwestern India. J Emerg Trauma Shock 2014;7:9-13
|How to cite this URL:|
Bhalla A, Das B, Som R, Prabhakar S, Kharbanda PS. Status epilepticus: Our experience in a tertiary care centre in Northwestern India. J Emerg Trauma Shock [serial online] 2014 [cited 2020 Jan 21];7:9-13. Available from: http://www.onlinejets.org/text.asp?2014/7/1/9/125632
| Introduction|| |
Status epilepticus (SE) is a medical emergency associated with high morbidity and mortality.  Increasing number of studies from India and around the world have tried to systematically examine trends in incidence, precipitants and outcome in patients with SE with an aim to look at potentially reversible factors. SE is defined as continuous seizure or repetitive discrete seizures with impaired consciousness in the interictal period.  It has also been defined as a condition in which two or more sequential seizures occur without recovery of full consciousness between the seizures.  It has numerous subtypes, but generalized convulsive status epilepticus and non-convulsive status epilepticus (NCSE) are the important clinical types. The diagnosis is difficult on the basis of clinical semiology alone and requires investigation like electro-encephalogram (EEG), especially in-patients having NCSE. 
12-30% of adults with a new diagnosis of epilepsy present with SE.  Central nervous system infections are commonly associated with SE and are an important cause of de novo refractory status epilepticus both in children and adults. , In adults precipitation of status is usually related to the withdrawal or reduction of antiepileptic drugs (AEDs), acute stroke or toxic/metabolic abnormalities. ,,
The recognition and rapid treatment of seizures is important during acute illness. , The failure to diagnose status epilepticus leads to high mortality. Neuropathologic consequences of SE are mostly due to continuous excitation of neurons. Delay in diagnosis and treatment may result in permanent vegetative state or cognitive difficulties. 
This study was undertaken to evaluate the profile of the patients and in hospital outcome of patients presenting with SE to the emergency department (ED) in a tertiary health-care institute in North-Western India.
| Patients and Methods|| |
All consecutive adult patients presenting to the ED at Nehru Hospital attached to PGIMER at Chandigarh between January 2009 to May 2010 with SE were prospectively enrolled in the study. Ethical clearance was obtained from the institute ethics committee before enrollment. Both newly diagnosed patients and known case of seizure disorder presenting with SE were enrolled. All patients were clinically examined and detailed history was recorded. Routine hematological and biochemical investigations were carried out at admission in all. EEG and computerized tomograms of head, both plain and contrast enhanced were carried out in all the patients. Magnetic resonance imaging (MRI) brain was done whenever possible for evaluation of etiology. Imaging studies were undertaken only after the control of SE as a part of work-up for the etiology. Standard guidelines were followed in treating SE. Seizure in patients presenting with SE for the first time, was controlled with injection lorazepam or injection diazepam, followed by dilantinization with injection phenytoin 20 mg/kg intravenous (iv) @ 50 mg/min or injection fosphenytoin 20 mg/kg @ 150 mg/min. If seizure persisted phenytoin or fosphenytoin was reloaded with 7 to 10 mg/kg. Injection valproate (25 mg/kg) or injection phenobarbital (20 mg/kg; if not controlled another 10 mg/kg @ 60 mg/min) was given as second line agents in patients with persisting seizures. In spite of this if seizure continued, injection midazolam perfusion or anesthesia with propofol were used. Patients having a pre-existing seizure disorder, presenting with status were given lorazepam/diazepam to control seizure, followed-by half-loading dose of the AED they were consuming earlier. All patients were followed-up daily in the hospital for a period until discharge or death and again followed-up in the neurology out-patient at the end of 2 weeks to look for immediate outcome. Data analysis was done using SPSS. Quantification of precipitating factors was done using proportion, mean and standard deviation.
| Results|| |
A total of 80 adult patients presented to the ED during the study period. The mean age of the patients was 38.43 ± 16.56 years (range 13-78 years). Male to female ratio was 4:1. Out of 80 patients, 46 cases were known case of seizure disorder. The age of onset of seizure in this subset was 33.95 ± 17.24 years (range 7-73 years) with duration ranging from 1 to 12775 days (35 years) before presenting with SE. 3 patients (7.5%) had been admitted earlier with SE. The mean interval between onset of SE to presentation in the emergency was 11.65 ± 13.86 h (range 2-72 h) with almost 60% presented within 6 h at our institution. The baseline clinical, hematological and biochemical parameters are described in [Table 1].
|Table 1: Baseline clinical, hematological and biochemical parameters of the study population|
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68 (85%) patients had generalized tonic clonic seizures (GTCS); which was the most common type of seizure in the study population. Four (5%) patients had partial seizure while 6 (7.5%) patients had partial seizure with secondary generalization. Only 2 (2.5%) patients had complex partial seizure. 57.5% of the study population had a history of seizure disorders in the past with GTCS being the most common seizure type noted in 91.30%. 97.5% had convulsive SE, whereas only 2.5% patient was noted to have non-convulsive SE.
55% of our study population was on AEDs at the time of presentation, with 68.18% out of them controlled on a single drug, while 31.82% were on multiple drugs. 45% of the study population presented with de novo SE and were not on any AEDs. 77.27% patients were on phenytoin while 22.73% patients were on clobazam and 18.18% patients were on sodium valproate. Among patients who were on AEDs presenting with SE, 90.91% had poor compliance with the drugs.
Benzodiazepines (Lorazepam/diazepam) with injectible phenytoin as loading dose were used in 97.5% of patients for as first line drugs. In 40 patients (50%), SE was controlled with use of first line agents. In patients where status couldn't be controlled, second line agents (phenobarbitone/valproate/levetiracetam) were used. SE was controlled in 65% (26/40) patient's refractory to first line drugs. In the remaining 14 patients (35%) midazolam infusion was initiated. All but two patients responded to second line agents. In the rest, SE couldn't be controlled, even after propofol infusion.
97.5% patients responded to AEDs and SE was controlled within mean time of 6.26 ± 7.30 h (range1 to 36 h). In 85% of cases, SE was controlled within 12 h of presentation. In six (7.5%) patients SE lasted for more than 24 h and in two it could not be controlled and was associated with mortality. After controlling of SE, 27.5% patients were discharged on a single drug and 70% patients were discharged on multiple drugs regime.
Among the study group, 62.5% patients had single precipitating factor while 30% patients had multiple factors. In 6 patients (7.5%), no obvious precipitating factor could be traced. Poor drug compliance was found to be the most common precipitating factor in 50% patients. Central nervous system (CNS) infection was the commonest cause in patients with de novo SE (44%). In 14 (17.5%) patients, status was precipitated by cerebrovascular accident (hemorrhagic/ischemic stroke) mainly in the older age groups. Alcohol intake/withdrawal was noted in 10 (12.5%) patients whereas in six (7.5%) patients obvious precipitant couldn't be traced.
Imaging and EEG findings in our study population are described in [Table 2] and [Table 3].
In our study group of 80 patients of SE, in 55% patients SE was controlled with no recurrence of seizure or complication and in 25% status was controlled, but had recurrence of seizure without any sequel. In 15% patients status was controlled, but with persistent sequel (cognitive and psychosomatic dysfunction, neurological deficit etc.) lasting for 2 weeks or more. Four (5%) patients expired, two patients due to uncontrolled SE and the other two probably due to underlying primary disease (hypertension, stroke and type 2 diabetes).
Respiratory depression (hypoxia, tachypnia) was the most common in hospital complication (45.5%), followed by cognitive dysfunction and residual neurological deficit (hemiparisis, paresthesia, nerve paresis etc.,) seen in 27.5%. Respiratory depression could not be clearly attributed to SE or drugs. Cardiac complications (arrhythmia, Atrioventricular block etc.) were noticed in two patients only. Most complication was transient and resolved within 24 h; however, in twelve patients sequel lasted for 2 weeks or more.
| Discussion|| |
In our study population, consisting mainly of North Indian patients, age varied from 14 years to 78 years with median of 38 years. In previous studies age has been documented to have a relationship with the etiology and type of SE. Infection as an etiology is more common in children, whereas drug default and toxic-metabolic causes are common in adults, who present to ED in SE. ,, Our results are also very similar with drug default being a major cause in patients with pre-existing seizure disorder and infections being common in patients having de novo SE.
Male preponderance in our study may be due to fact that early medical attention is generally provided to the males in the family, resulting in male:female ratio being skewed in favor of the former. Majority (95.5%) of our study population had convulsive status. Similar findings have been noted in earlier studies from North central India, where it was found that up to 92% of SE patients had convulsive status and 8% had non-convulsive SE.  This is in contrast to a study conducted by Di Bonaventura et al. in Italy, where the authors could identify 28 convulsive and 22 non-convulsive SE on video EEG.  This suggests that clinically most patients would present with convulsive status but non-convulsive status may be picked up more efficiently by video EEG or continuous EEG monitoring, especially in patients who are critically-ill and on life supports. ,,
Generalized tonic clonic seizure was the most common type of seizure noticed at initiation in our study group, as has been the experience in other Indian studies as well. ,,, However, it is possible that a focal onset may have not been noticed by the bystanders/relatives, therefore not documented.
In our study, most common precipitant of SE in patients already on AED was poor compliance which is in contrast to patients presenting with de novo SE having CNS infection. Similar findings have been noted in other studies from South Asian countries. ,, The American experience is somewhat different where AED non-compliance was the leading cause followed by alcohol.  Alcohol abuse is a major precipitant of SE in the west event rates ranging between 9 to 25% of cases. , Seizures in alcohol withdrawal patients are relatively more common as compared to alcohol intoxication. Although, alcohol use/abuse is very common in North Western part of India, yet only 12.5% patients had alcohol related SE. Alcohol withdrawal was more common cause of status than alcohol intoxication in our study group. This indicates that although not very common, but alcohol withdrawal/intoxication may be kept in mind as possible precipitant of SE. Early identification and prompt treatment of alcohol withdrawal seizures is recommended to prevent SE. 
Stroke is also an important cause of symptomatic epilepsy, especially in the elderly.  Studies have shown that the frequency of seizures in stroke ranges between 2.3 to 14%. , SE can be a presenting symptom of an acute stroke and can lead to increased mortality. Both hemorrhagic and ischemic stroke can result in epilepsy.  In our study population, stroke was an important cause of new onset SE, exclusively noted in the elderly population.
Hypertension, diabetes, tuberculosis were the commonly associated co- morbidities found in our study population. Both diabetes and hypertension can result in both micro and macro vascular complications resulting in seizures and sometimes SE.  Similar findings were noted in a retrospective study, where up to 42% patients presenting with SE had an underlying disease.  Whether co-morbidity had a direct adverse effect on SE in our population could not be ascertained as numbers of patients was small.
In our study, phenytoin and benzodidepines (lorazepam diazepam) were first line AEDs. Both phenytoin and benzodidepines were used together for termination and phenytoin was used as maintenance AED. The Veterans' Affairs SE Cooperative Study found that lorazepam had the highest rate of termination (65%); although, differences were not significant compared with diazepam plus phenytoin (56%) and phenobarbital when used alone (58%).  In this study Phenytoin alone (43%) was found to be statistically inferior to lorazepam. In our study combination of lorazepam or diazepam and phenytoin for termination of status was successful in 55% of our patient population. Our results are comparable to other Indian studies both in adults and pediatrics population. , Due to small number of patients in our study group, comparison among different combination of AEDs could not be done.
Levetiracetam is preferred second line drug in controlling status as it doesn't cause respiratory depression or hypotension in contrast to midazolam and propofol.  iv levetiracetam in moderate doses is known to be efficacious and well-tolerated alternative treatment for focal (simple and complex focal) and myoclonic SE. , In our study, levetiracetam was successfully used as a second line agent in 20% patients where first line AEDs failed.
Once first and second-line agents have not been successful in termination of the event, the patient can be considered as refractory status epilepticus (RSE).  Midazolam has been as effective in RSE as propofol (64% vs. 67%)  fear of the side-effects have resulted in increasing use of midazolam infusion at our emergency for RSE. In our study group, midazolam infusion was able to control RSE in 85% patients.
In terms of morbidity, neurological impairment after SE is usually the greatest concern. Subsequent complications might affect any organ system and will eventually lead to mortality, which ranges between 10% and 40%. ,,[ 25] Although, data in adults is sparse, studies in children have shown that neurological disability follows in upto 15% of patients.  Neurological complication were seen in 27.5% (neurodeficit, cognitive dysfunction etc.) in our study group, which is a slightly higher than reported in the literature.
In our study group mortality was 5% patients, which is much lower than the reported mortality in other Indian studies. , In one such study of 117 patients, mortality was 29% and it was found to be higher in elderly as compared to children.  Poor outcome in patients with SE, has been attributed to improper and delayed management resulting in complication. , Mortality appears to be related to the underlying cause and to the level of secondary brain injury too. CNS anoxia and infection carry higher mortality in patients with SE. ,, In our study, prompt control and intensive monitoring for complication, early and prompt management of complication could be the factors associated with low mortality.
| Conclusion|| |
SE in our study population was seen in diagnosed cases of seizure disorders, who were noncompliant with prescribed medications. CNS infections and structural lesions of the brain were the most common causes of new onset SE. Stroke as a cause of SE was exclusively seen in elderly. Most of our patients had a convulsive status with GTCS. Phenytoin and benzodiazepine combination was successful in controlling status in half the study group. Levetiracetam and phenobarbitone were effective second line agents. Prompt and effective control of the status resulted in better survival in our study group.
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Parampreet S Kharbanda
Department of Neurology and Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]