Etiology of new-onset seizures in adult patients of different age groups presenting to the emergency department in North India and their outcomes

ABSTRACT

Introduction:

Seizures are one of the most common neurological emergencies encountered in both urban and rural India. There is only limited research work on the etiology of new-onset seizures in adult patients of different age groups presenting to the emergency department, especially from the Indian sub-continent. A new-onset seizure can be the first presentation of stroke, or it may be a symptom of brain infections, metabolic abnormality, brain tumor, systemic disease, or an early phase of epilepsy, which needs scrutiny and appropriate management. A dedicated study of the underlying etiology of new-onset seizures among different age groups and their incidence and prevalence can help in the prognostication and clinical management of these patients.

Materials and Methods:

This was a prospective observational cross-sectional study conducted in the Emergency Medical Out-patient Department and emergency medical ward of the Post-graduate Institute of medical education and research, Chandigarh.

Results:

In our research, males out-numbered females. The most common seizure type recorded in our study was generalized tonic-clonic. In the younger age group between 13 and 35 years, infective etiologies were dominant. In the middle age group between 36 and 55 years, cerebrovascular accidents were the dominant etiology, followed by infective causes and metabolic causes. In the older age group above 55 years, the most dominating etiology found was cerebrovascular accident. Almost 72% had abnormal brain imaging. The most common abnormality found was ischemic infarcts. The second most common abnormality detected was a meningeal enhancement. A small percentage of patients had an intra-cranial bleed, and a very small percentage had a subarachnoid hemorrhage.

Conclusions:

In younger patients, infections such as tubercular and pyogenic meningitis and cerebral malaria are the most common causes of new-onset seizures, followed by malignancy and metabolic causes, in descending order. In the middle age group, stroke is the most common etiology, followed by central nervous system (CNS) infections and metabolic causes, in descending order. In elderly patients, stroke is the leading etiology for new-onset seizures. Physicians working in rural and remote areas routinely face challenges in managing patients with new-onset seizures. Knowledge of different etiologies in different age groups will equip them to make informed decisions regarding investigations and treatment of patients with new-onset seizures. It also encourages them to aggressively search for CNS infections, especially in younger patients.

Introduction

Background/rationale/objectives

Seizures are one of the most common neurological emergencies encountered in both urban and rural India.[1] Seizures are one of the appreciable causes of mortality and morbidity in patients presenting to the emergency department. There is only limited research work on the etiology of new-onset seizures in adult patients of different age groups presenting to the emergency department, especially from the Indian sub-continent. Primary care physicians working in rural and remote areas routinely face the challenge of managing patients with new-onset seizures. Knowledge of different etiologies in different age groups will equip them to make informed decisions regarding investigations and the treatment of patients with new-onset seizures. The new-onset seizure was defined as the seizure occurring for the first time in the person’s life span within the past 24 hours.[2] A new-onset seizure can be the first presentation of stroke, or it may be a symptom of brain infections, metabolic abnormality, brain tumor or systemic disease, or the early phase of epilepsy, which needs scrutiny and appropriate management.[3] The frequency of seizures in the general population is about 1 in 10 during their lifetime. The bulk of these seizures is acute symptomatic seizures that occur secondary to acute central nervous system (CNS) insult, which may be structural or metabolic or infectious in nature and is not related to epilepsy.[4] The etiology of seizures can be diagnosed in the majority of patients.[5] Metabolic causes are a more common cause of new-onset seizures in critically ill patients.[6] A dedicated study of the underlying etiology of new-onset seizures among different age groups and their incidence and prevalence can help in the prognostication and clinical management of these patients.

Study design and Setting

This was a prospective observational cross-sectional study conducted in the Medicine Emergency of the Post-graduate Institute of medical education and research, Chandigarh. Patients were enrolled in the study from July 1, 2020 to December 31, 2021.

Outcomes

The patient was monitored for 7 days after giving treatment as per the need. After 7 days, the final outcome of patients was evaluated for study as

1. Etiology.

2. Outcomes: A) Discharged, B) Died, and C) Hospitalization

Inclusion criteria

All patients with new-onset seizures presenting to the medical emergency unit whose age was 13 years were enrolled in the study.

Exclusion criteria

All those patients who had a previous history of epilepsy or seizure disorder or patients younger than 13 years and pregnant females were excluded.

Methodology

Ninety patients were enrolled in the study. They were divided into three different groups based on their age groups. Group 1 includes patients 13–35 years of age. Group 2 includes patients of 36–55 years of age. Group 3 includes patients above 55 years of age. Each group had 30 patients in it. Informed consent was obtained from each patient before enrollment. All patients’ complete medical history and clinical examinations were performed. All patients’ complete bio-chemical profiles were analyzed and basic workups were performed, which included hemograms, liver function tests, kidney function tests, random blood sugar, and serum electrolytes. Brain imaging was performed in all the patients enrolled in the study. Lumbar puncture and cerebro-spinal fluid (CSF) examination were performed only when it was clinically indicated.

Sample size calculation

Because there is a previous study performed that looked at the etiology of new-onset seizures in different age groups, we looked at 6-month data of PGI medicine emergency and found that prolonged hospital stay (7 days or more) was found in 80%, 50%, and 20% of the patients with new-onset seizures in the age group of >55 years, 36–55 years, and 13–35 years, respectively. Therefore, we recruit 30 patients in each group (a total of 90 patients) with 80% power of study and 5% level of significance to find out the significant comparison among groups.

Statistical methods

Non-parametric Mann–Whitney U-test was used for statistical analysis of two groups with skewed data or scores. When the data were normally distributed and there were more than two groups, a one-way ANOVA followed by a Bonferroni post hoc multiple comparisons test was used. When there are more than two groups, the Kruskal Wallis test is used to compare the values of skewed data. Pearson Chi-square tests or Fisher’s exact tests were used to compare categorical data. To determine the relative importance of various confounding variables in triggering seizures, a multi-variate regression analysis is used. The significance threshold for all statistical tests is 0.05, and they are all two-sided. IBM SPSS STATISTICS is used for the analysis (version 22.0).

Ethical considerations

Ethics approval was given by the independent institute ethics committee. Consent to participate in the study was taken from all patients.

Results

Participants

As depicted in Figure 1, 90 patients who presented with new-onset seizures to medicine emergency were enrolled. Thirty patients were recruited in each group. Out of the total of 90 patients, 54.4% (n = 49) were male and 45.6 (n = 41) were female.

Figure 1.

Gender distribution of patients with new-onset seizures presenting to the emergency

Clinical presentation

The most common seizure type recorded in our study was generalized tonic-clonic seizures, present in 98.9% of patients, whereas complex partial seizures were seen in 1.1% of patients only. The majority of patients (92.2%) had one to five episodes of seizure, whereas 5.6% of patients were found to have six to ten episodes and 2.2% were found to have 10–15 episodes of seizure. As depicted in Figure 2, the most common associated complaint was fever, which was present in 38.9% (n = 35) of patients. Altered mental status was the second most clinical presentation which was seen in 30% (n = 27) of patients. Hemiparesis was present in 16.7% (n = 15) of patients. Headache was present in 13.3% (n = 12). Eye swelling was present in 1.1% (n = 1) of patients.

Figure 2.

Chief complaints in patients with new-onset seizures presenting to the emergency

Past history

Out of 90 patients, the majority (81.1%) (n = 73) had no past history, whereas 7.7% (n = 7) had hypertension, 5.6% (n = 5) had diabetes, and 5.6% (n = 5) had pulmonary TB.

Bio-chemical profile

Metabolic abnormality was present in 12% (n = 11) of the patients. The most common metabolic abnormality found was hyponatremia 6.3% (n = 7), followed by hypoglycemia, which was 2.3% (n = 3), and the least common was hypocalcemia 0.9% (n = 1). The mean Na + was 129.9 ± 25.3, the mean K + was 5.3 ± 7.7, the mean Mg++ was 1.1 ± 0.00, the mean Ca++ was 9.8 ± 2.3, the mean blood urea was 57.7 ± 6.9, the mean serum creatinine was 1.2 ± 1.8, and the mean RBS of the patients was 109.8 ± 117.2.

Neuro-imaging

Brain imaging was performed for all the patients enrolled in the study. 81.1% (n = 73) had undergone non-contrast computerized tomography (NCCT) head, whereas 18.9% (n = 17) patients had undergone both magnetic resonance imaging (MRI) and NCCT head. Almost 72% (n = 80) had abnormal brain imaging. The most common abnormality found was ischemic infarcts in 26.1% (n = 29) of patients. In 5.4% (n = 6) patients, intra-cranial bleed was seen. Only 2.7% (N = 3) had a subarachnoid hemorrhage, and 0.9% (n = 1) of patients had an extradural hematoma. 5.4% (n = 6) patients had meningeal enhancement and feature suggestive of pyogenic meningitis. Nine patients (8.1%) had meningeal enhancement along with hydrocephalus, suggestive of tubercular meningitis. In nine patients (8.1%), MRI showed hyper-intensity involving the cortical and the sub-cortical regions of bilateral temporal, frontal lobes, and insula on T2-weighted images suggestive of viral encephalitis. Three (2.7%) patients had space-occupying lesions in the brain. One patient (0.9%) had involvement of paranasal sinuses along with orbit, suggestive of mucormycosis. 5.4% (n = 6) had non-specific hyper-intensities located in the bilateral periventricular white matter and/or bilateral thalamic regions. 9% (n = 10) had isolated diffuse cerebral edema. Ten (9%) patients had normal brain imaging.

Cerebro-spinal fluid profile

CSF workup was carried out in 35 patients. Among them (N = 21), 23.3% of patients found to be G/S-negative, whereas 3.3% (N = 3) were G/S-positive; 2.2% (N = 2) of the patients were gene expert-negative, whereas 8.9% (N = 8) were gene expert-positive; 16.7% (N = 15) were AFB smear-negative, whereas 7.8% (N = 7) were AFB smear-positive; and 23.3% (N = 21) patients were cryptococcal antigen-negative, whereas 1.1% (N = 1) patients were found to be cryptococcal antigen-positive. In CSF, the mean ADA of the patients was 8.2 ± 7.6, the mean total cell count was 313.9 ± 226.7, the mean lymphocytes were 75.1 ± 13.5, the mean neutrophils were 27.0 ± 13.9, the mean protein was 136.1 ± 107.5, and the mean glucose was 58.3 ± 19.4.

Outcomes

As depicted in Figure 3, outcomes were evaluated after 7 days from admission. Out of 90 patients, 56.7% (n = 51) patients were discharged from the hospital, 28.9% (n = 26) patients were hospitalized (shifted to either an intensive care unit or ward), 5.5% (n = 5) patients were Leave Against Medical Advice (LAMA), and 8.9% (n = 8) patients have died.

Figure 3.

Outcomes of patients with new-onset seizures presenting to the emergency at 7 days of hospitalization

Etiology of new-onset seizures

As depicted in Figure 4, stroke was the most common etiology encountered in the study; it was present in 40% (n = 36) of the patients. It was followed by metabolic causes such as hypocalcemia, hypoglycemia, and hyponatremia, which were present in 12.2% (n = 11) of patients. Tubercular meningitis was present in 10% (n = 9) of patients. Ten percent (n = 9) had viral meningoencephalitis, and acute febrile illness precepted seizure was present in 5.6% (n = 5). Bacterial meningoencephalitis was present in 5.6% (n = 5) patients, 4.4% (n = 4) had cerebral malaria, and malignancy was present in 3.3% (n = 3). A small number of patients (1.1%, n = 1) had uremic encephalopathy, post-coronavirus disease (COVID) seizure was present in 1.1% (n = 1) patients, rhino cerebral mucor mycosis was present in 1.1% (n = 1) patients, cryptococcal meningitis was present in 1.1% (n = 1) patients, and NMDA encephalitis was also present in 1.1% (n = 1) patients.

Figure 4.

Various etiologies of new-onset seizures in patients presenting to the emergency

Age correlation with different etiologies of new-onset seizures

As shown in Figure 5, in the younger age group between 13 and 35 years, the most common etiology was tubercular meningitis, which was present at 16.7% (n = 5), and an almost similar number of patients had acute febrile illness 16.7% (n = 5). Bacterial meningoencephalitis was present in 10% (n = 3) of patients. Not even a single patient in this group had a stroke. Uremic encephalopathy was present in 3.3% (n = 1). Malignancy was present in 10% (n = 3) of patients. Cerebral malaria was present in 10% (n = 3) of patients. Viral meningoencephalitis was present in 13.3% (n = 6) and 10.0% (n = 3) who had metabolic encephalopathy, that is, hypocalcemia, hypoglycemia, or hyponatremia. In the age group between 36 and 55 years, 6.7% (n = 2) had bacterial meningoencephalitis, 36.7% (n = 11) of the patients had cerebrovascular accident, 13.3% (n = 4) had tubercular meningitis, and 3.3% (n = 1) had post-COVID seizure, 3.3% (n = 1) had post-stroke seizure, 3.3% (n = 1) had cerebral malaria, 3.3% (n = 1) had viral meningoencephalitis, and 23.3% (n = 7) had metabolic encephalopathy (hypocalcemia/hypoglycemia, hyponatremia). In the age group above 55 years, the majority of the patients had cerebrovascular accident, 83.3% (n = 25) and 3.3% (n = 1) had post-stroke seizure, 3.3% (n = 1) had rhinocerebral mucormycosis, 3.3% (n = 1) had NMDA encephalitis, 3.3% (n = 1) had metabolic encephalopathy (hypocalcemia/hypoglycemia, hyponatremia), and 3.3% (n = 1) had cryptococcal meningitis.

Figure 5.

Age correlation with different etiologies of new-onset seizures in patients presenting to the emergency

Age correlation of outcomes

As depicted in Figure 6, in the age group between 13 and 35 years, 6.7% (n = 2) patients were dead, 53.3% (n = 16) were discharged, and 40% (n = 12) were still hospitalized. In the age group between 36 and 55 years, 6.7% (n = 2) patients were dead, 60% (n = 18) were discharged, 6.7% (n = 2) had left against medical advice, and 26.6% (n = 8) patients were still hospitalized. In the age group above 55 years, 13.3% (n = 4) patients were dead, 56.7% (n = 17) were discharged, 10% (n = 3) had LAMA, and 20% patients were still hospitalized.

Figure 6.

Age correlation of outcomes in patients with new-onset seizures presenting to the emergency

Discussion

New-onset seizures are of great clinical importance because they are frequently linked to underlying medical conditions. When the underlying etiology of a patient’s seizures can be diagnosed with the help of brain imaging and laboratory examination, the related mortality and morbidity can be reduced. There is a paucity of data on the etiology of new-onset seizures, especially when categorized in different age groups. In India, primary care physicians form the backbone of the health system in rural and semi-urban India. The majority of new-onset seizures are managed by primary care physicians. A minority of primary care physicians rate themselves very comfortable with seizure patients. Most of the primary care physicians refer the majority of their seizure patients to a neurologist.[7] Knowledge of different etiologies in different age groups can boost the confidence of treating primary care physicians and will equip them to make informed decisions regarding investigations and treatment of patients with new-onset seizures and can decrease unnecessary referrals to the tertiary care center.

Gender

In our research, males out-numbered females, 54.4% of the patients were male and 45.6% were female, with an average age of 44.6 years, and the male-to-female ratio was 1.2 to 1. Our results correspond with other studies performed by Muralidhar and Venugopal[8] (2.12:1), Hirani and Shrivastva[9] (1.17:1), and Sendil et al.[10] (1.63:1), where men out-number females.

Type of seizure

The most common seizure type of seizure recorded in our study was generalized tonic-clonic seizures, present in 98.9% of patients, whereas complex partial seizure was seen in 1.1%. Previous studies performed by Narayanan and Murthy,[11] Kanitkar et al.,[12] Sendil et al.,[10] and Hirani and Shrivastva[9] also reported a higher prevalence of generalized tonic-clonic seizures in adults (55%, 70%, 64%, and 60%, respectively). In our study, the percentage of patients with generalized tonic-clonic seizures was more, probably because all patients in the study were enrolled in emergency departments and not from outdoor patient departments.

Etiology of seizures

In our research, we found that new-onset seizures have different etiologies in different age groups. In the younger age group between 13 and 35 years, infective etiologies were dominated, which was followed by metabolic and uremic causes. Malignancy was rare. Not even a single patient in the younger age group had a cerebrovascular accident. Studies performed by Chalasani and Kumar[13] have also described identical etiologies. A study on the etiology of seizures in different age groups by Quraishi et al.[14] disclosed that CNS infections were the most common cause of seizures in the age groups of 15–20 years (77.8%) and 21–30 years (57.1%). A study by Pradeep et al.[15] found that 44% of patients with seizures that began at the age of 20 or more had idiopathic causes, with brain infections, neurocysticercosis, tuberculoma, post-traumatic, and tumor etiologies being the most prevalent. In the middle age group between 36 and 55 years, cerebrovascular accidents were the dominant etiology present in 36.7% of the patients. The second most common etiology in this group was CNS infection. The third most common cause in this age group was metabolic abnormalities. In the older age group above 55 years, the most dominating etiology found was cerebrovascular accident, followed by infective etiology. Stroke was shown to be the most prevalent cause of seizures in older adults, according to a study by Kanitkar and colleagues.[12] According to studies by Jiménez et al.[16] and Hirani and Shrivastva,[9] CNS infections (38%), stroke (30%), and idiopathic seizures (25%) were the most common causes of adult-onset seizures. In comparison to these studies, our study revealed that infective causes were predominate in young patients and stroke became the dominant cause as age increased.

Neuro-imaging correlation

Brain imaging was performed for all the patients enrolled in the study. Almost 72% had abnormal brain imaging. The most common abnormality found was ischemic infarcts. The second most common abnormality detected was a meningeal enhancement. A small percentage of patients had an intra-cranial bleed. Studies performed by Sinha et al.[17] noticed that brain imaging was normal in 40.7% of cases; in the remaining patients, the most frequent CT findings were infarct (22%), diffuse edema (10%), intra-cranial hemorrhage (9%), tumors (7%), calcified granuloma (5%), neurocysticercosis (3%), and brain atrophy (3%). Pannag and Ravi[18] reported that MRI brain was normal in 46% and the most common pathological findings on MRI were post-ischemia/hemorrhagic changes (20%), followed by tuberculoma (9.7%), tumor (9%), mesial temporal sclerosis (3%), neurocysticercosis (2.4%), encephalitis (2.4%), vascular malformation (1%), and progressive multi-focal leukoencephalopathy (0.6%). Our results are different from these studies; only 9% of patients had normal brain imaging, and the incidence of stroke and tuberculomas were similar to these studies.

Outcomes of new-onset seizures

In our study, the mortality in younger and middle age groups was 6.7%. In the older age group, mortality almost doubled to 13.3%. According to a recent study, young adults aged between 16 and 24 may have a six-fold increased risk of epilepsy-related death, a disorder in which nerve cell activity in the brain is disturbed, causing seizures.[19] Our results are different from this study because most of the young patients with new-onset seizures have infective etiology and did not have epilepsy. New-onset seizure in elderly patients is particularly associated with higher mortality when diagnosed after another neurologic condition such as stroke or Parkinson’s disease. In our study, the majority of elderly patients had a stroke, which also explains the reason for higher mortality.

Conclusions

In younger patients, CNS infections are the most common cause of new-onset seizures, followed by malignancy and metabolic causes, in descending order. In the middle age group, stroke is the most common etiology, followed by CNS infections and metabolic causes, in descending order. In elderly patients, stroke is the leading etiology for new-onset seizures.

Strengths of the study

This study was performed in the emergency of a top tertiary care hospital in North India.

Limitations of the study

The biggest limitation was that it was a single-center study.

Conclusions

In younger patients, CNS infections are the most common cause of new-onset seizures, followed by malignancy and metabolic causes, in descending order. In the middle age group, stroke is the most common etiology, followed by CNS infections and metabolic causes, in descending order. In elderly patients, stroke is the leading etiology for new-onset seizures.

Abbreviations- NOS - New-onset seizure, MRI - Magnetic resonance imaging, RBS - Random blood sugar, LAMA - Leave Against Medical Advice, CNS - Central nervous system

Authors’ contributions

Dr. MS Bhatia proposed the idea of the study. Dr. Gaurav collected the data. Dr. Saurabh revised the data. Dr. MS Bhatia, Dr. Sahil, Dr. Ritu revised the results and wrote the manuscript. All authors have read and approved the manuscript.

Availability of data and materials

Data are available on genuine request to the corresponding author.

Key Points

1. In younger patients, CNS infections are the most common cause of new-onset seizures.

2. In the middle age group, patient stroke is the most common etiology, followed by CNS infections and metabolic causes, in descending order.

3. In elderly patients, stroke is the leading etiology for new-onset seizures.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.