Abstract
Background:
Epilepsy, characterized by recurrent unprovoked seizures, poses a significant global burden on individuals and healthcare systems. Accurate identification of underlying causes is vital for optimal intervention. However, studies reveal a lack of standardized approaches, potentially resulting in unnecessary investigations.
Objective:
We aimed to highlight the importance of avoiding unnecessary testing to minimize healthcare costs and resource waste.
Methods:
In the Emergency Department of King Fahd Hospital of the University (KFUH) in Alkhobar, a retrospective cross-sectional study encompassed 190 patients presenting with seizures from January 1, 2020, to December 31, 2022. The study aimed to elucidate the epidemiological profile and distinguish clinical and demographic factors between new onset seizures and known cases.
Results:
The study included 190 epilepsy cases, with 51.1% known and 48.9% new onset. Generalized tonic-clonic seizures were prominent (43.2%), and non-compliance (24.2%) was a leading cause. New onset seizures were associated with abnormal CT findings (p=0.025), drug use (74.2%), and intoxication (6.5%). Demographically, Saudis showed higher new onset prevalence (82.8%, p=0.001).
Conclusion:
The average length of stay was 5.93 hours, and the distribution of new vs. known cases was nearly equal among the 190 patients. Laboratory findings showed no significant associations with either group, mostly falling within the normal range. To optimize care further, we recommend continued refinement of protocols, emphasis on medication compliance.
Keywords: seizure, Epilepsy, emergency, medication, neurology
1. BACKGROUND
Epilepsy is a seizure disorder defined as the occurrence of two or more unprovoked seizures that are 24 hours apart. (1) Seizures, characterized by sudden and involuntary changes in neurological function, present a considerable burden on individuals and healthcare systems worldwide. (2-4) In the United States (US), seizures account for about 1% of emergency department (ED) (5) visits, and it is reported that 11% of individuals will have at least one seizure in their lifetime. (6) Most cases of seizures encountered in the ED setting are due to secondary medical causes or substance abuse. (6)
Timely and accurate recognition of secondary or precipitating causes is crucial for administering appropriate interventions, optimizing patient outcomes, and preventing potential complications. (6) Laboratory and radiological testing play a pivotal role in the comprehensive assessment and accurate diagnosis of medical conditions, including seizures, providing invaluable insights into the underlying causes and seizure types and guiding effective treatment strategies. Nonetheless, unnecessary overordering of laboratory tests can lead to increased costs and misguided management. As a result of a lack of standardized ED approaches to acute seizures, studies have shown that up to fifty percent of all investigations ordered were deemed unnecessary. (7) In this research, we conducted a retrospective, cross-sectional study at the King Fahd Hospital of the University, Al Khobar, analyzing the medical records of 190 patients who sought treatment in the Emergency Department for seizures between 2020 and 2022. Our study aimed to explore the epidemiological profile of seizure presentations and assess the significance of laboratory tests in the evaluation process.
2. OBJECTIVE
We aimed to highlight the importance of avoiding unnecessary testing to minimize healthcare costs and resource waste.
3. MATERIAL AND METHODS
A retrospective cross-sectional study was conducted in the Emergency Department (ED) at King Fahd Hospital of the University (KFUH) which is situated in Alkhobar. An academic tertiary center, KFUH offers medical services to a substantial patient population across the cities of Alkhobar and Dhahran. Caring for an estimated count of around 300,000 people in the area, the hospital stands as a prominent healthcare provider, offering an array of medical services.
The study focused on a cohort of 492 patients who sought medical attention between the period of January 1, 2020, and December 31, 2022, with seizures as their chief complaint. The primary objective of this investigation was to provide insights into their epidemiological profile and distinguish between the different factors, both clinically and demographically, between new onset seizures and known cases of seizures.
From this initial patient pool, an inclusion criterion was established to encompass adult patients aged 18 and above, with a deliberate emphasis on those with complete and comprehensive medical records. 183 patients below the age of 18 were excluded to maintain a focus on the adult population. An additional 74 patients were excluded due to incomplete medical information and lastly, 45 patients were omitted from the study due to instances of misdiagnosis. This approach yielded a final cohort of 190 patients.
Data was analyzed by IBM SPSS.21. All categorical variables were presented as frequencies and percentages while all continuous data was presented as Median (IQR) or mean (±SD). Chi-square test was used to check the association between variables, Mann Whitney U test was used to compare the medians of lab parameters. Statistical significance was set at P < 0.05.
4. RESULTS
The study population consisted of 110 males (57.9%) and 80 females (42.1%), with an age range of 18 to 89 years (mean ±SD age 36.8 ±17.6 years). The majority of cases 119 (62.6%) had age 21 – 40 years. Out of the total, 171 (90%) were Saudi and 19 (10%) were non-Saudi. Table-1
Table-1. Demographics of cases (n=190).
| Frequency | Percent | ||
|---|---|---|---|
| Gender | Males | 110 | 57.9 |
| Females | 80 | 42.1 | |
| Age | < 20 | 17 | 8.9 |
| 21 - 40 | 119 | 62.6 | |
| 41 - 60 | 31 | 16.3 | |
| > 60 | 23 | 12.1 | |
| Nationality | Saudi | 171 | 90 |
| Non-Saudi | 19 | 10 |
The majority of patients 82 (43.2%) had generalized tonic-clonic seizures, while 9 (4.7%) had Status Epilepticus, 6 (3.2%) had tonic seizures, 4 (2.1%) had focal onset seizures and 86 (45.3%) unknown. Non-compliance to medicine was the most common cause of seizure found in 46 (24.2%) cases, Structural was found in 12 (6.3%) cases, and the cause was unknown in 107 (56.3%) cases. CT was found abnormal in 57 (30%) of cases. The average (SD) length of stay in ED was 5.93 (±3.4) hours Table-2
Table-2. Clinical Characteristics of cases (n=190).
| Frequency | Percent | ||
|---|---|---|---|
| Seizure Types | Generalized Tonic-Clonic | 82 | 43.2 |
| Status Epilepticus | 9 | 4.7 | |
| Tonic | 6 | 3.2 | |
| Focal | 4 | 2.1 | |
| Clonic | 2 | 1.1 | |
| Post Traumatic | 1 | 0.5 | |
| Unknown | 86 | 45.3 | |
| General Causes of Seizure | Non-Compliance to medicine | 46 | 24.2 |
| Structural | 12 | 6.3 | |
| Intoxication | 7 | 3.7 | |
| Metabolic | 7 | 3.7 | |
| Infections | 5 | 2.6 | |
| Psychogenic | 3 | 1.6 | |
| Others | 3 | 1.6 | |
| Unknown | 107 | 56.3 | |
| Specific Causes of Seizure | Breakthrough Seizure | 46 | 24.2 |
| Stroke | 6 | 3.2 | |
| Uremic Encephalopathy | 5 | 2.6 | |
| Amphetamine | 3 | 1.6 | |
| Hyperglycemia | 2 | 1.1 | |
| Psychogenic | 3 | 1.6 | |
| Others | 18 | 9.5 | |
| Unknown | 107 | 56.3 | |
| Triage | I | 2 | 1.1 |
| II | 9 | 4.7 | |
| III | 106 | 55.8 | |
| IV | 73 | 38.4 | |
| Not done | 89 | 46.8 | |
| CT Findings | Normal | 70 | 36.8 |
| Abnormal | 31 | 16.3 | |
| Length of Stay in ED Hours Mean (SD)=5.93 (±3.4) hours |
≤ 5 | 93 | 48.9 |
| >5 - 10 | 72 | 37.9 | |
| > 10 | 25 | 13.2 |
Figure 1: Flowchart of patients included in the study.
Out of 190 diagnosed cases of epilepsy, 97 (51.1%) were known cases and 93 (48.9%) cases presented with new onset of seizure. Figure-2
Figure-2. Onset of Seizures (n=190).
A comparison of laboratory parameters between known cases and new cases of Seizure is presented in Table-3. All the parameters were statistically similar in known cases and new cases of seizure. There was no significant difference found between two groups (p-values>0.05)
Table-3. Comparison of laboratory Parameters between known cases and New cases of Seizure (n=190). IQR=Inter-Quartile Range, WBC=White Blood Cell, BUN= blood urea nitrogen, SGOT= serum glutamic-oxaloacetic transaminase, SGPT= Serum Glutamic Pyruvic Transaminase, LDH= Lactate dehydrogenase.
| Normal Values | Median (IQR) | P-Values | |||
|---|---|---|---|---|---|
| Overall | Seizure | ||||
| Known Cases | New Onset | ||||
| WBC | 4.0 -11.0 | 7.9 (5.7 – 10.3) | 8.15 (5.83 – 11.13) | 7.35 (5.7 – 10.1) | 0.372 |
| Hemoglobin | 13.0-18.0 | 13.1 (11.7 – 14.9) | 12.95 (11.3 – 14.4) | 13.4 (11.8 – 15.1) | 0.134 |
| BUN | 8.4-25.7 | 11 (9 – 15) | 10 (8 – 15) | 11 (9 – 15) | 0.475 |
| Creatinine | 0.82 | 0.8 (0.7 – 1) | 0.79 (0.68 – 0.98) | 0.82 (0.7 – 1.05) | 0.267 |
| SGOT | 5.0 – 34.0 | 20 (15 – 26) | 19 (15 – 26) | 20 (15 – 26) | 0.805 |
| SGPT | 5.0 – 55.0 | 17 (11.5 – 27.5) | 17 (11 – 28) | 17 (12 – 25.25) | 0.994 |
| LDH | 125 – 220 | 207 (175.5 – 256.5) | 231.5 (187 – 274.5) | 244.5 (179 – 285) | 0.552 |
| Lactic Acid | 0.5 – 2.2 | 1.9 (1.4 – 3) | 1.55 (1.28 – 3.2) | 2.17 (1.36 – 3.07) | 0.403 |
| Creatine kinase | 30.0 -200 | 123.5 (67.8 – 181.5) | 125.5 (71.8 – 180.5) | 118 (64 – 189.5) | 0.909 |
| pH | 7.35 -7.45 | 7.4 (7.3 – 7.4) | 7.37 (7.32 – 7.4) | 7.37 (7.33 – 7.4) | 0.986 |
| HCO3 | 22 – 26 | 24.4 (21.4 – 25.8) | 24.7 (21.2 – 26.1) | 24 (21.4 – 25.5) | 0.323 |
| PCO2 | 35 – 45 | 45.5 (41.1 – 51.2) | 45.4 (41.9 – 51.05) | 45.6 (40 – 51.4) | 0.422 |
| Blood Glucose | 70 -140 | 108 (95 – 137) | 109 (96 – 136) | 104 (95 – 143.75) | 0.737 |
| Magnesium | 1.6 -2.6 | 2 (1.8 – 2.2) | 1.96 (1.8 – 2.12) | 1.97 (1.8 – 2.2) | 0.46 |
| Phosphorus | 2.3 – 4.7 | 3.5 (2.8 – 4.1) | 3.5 (2.7 – 4.1) | 3.4 (2.8 – 4.1) | 0.925 |
| Sodium | 136 – 145 | 139 (137 – 141) | 139 (137 – 141) | 139 (137 – 140.25) | 0.93 |
| Calcium | 8.4 – 10.2 | 9.2 (8.8 – 9.6) | 9.2 (8.7 – 9.6) | 9.2 (8.9 – 9.6) | 0.95 |
Association of demographics of patients with a new onset of seizures is presented in Table-4. Gender distribution was statistically same in both groups (p=0.4). Proportion of new onset of seizure was significantly high in Saudis 77 (82.8%) as compared to non-Saudis 16 (17.2%) (p=0.001), New onset of seizure was significantly associated higher age group of cases 17 (18.3%) (p=0.04).
Table-4. Association of demographics of patients with a new onset of seizures (n=190).
| Seizure | P-values | |||
|---|---|---|---|---|
| Known Cases | New Onset | |||
| Gender | Males | 53 (54.6%) | 57 (61.3%) | 0.4 |
| Females | 44 (45.4%) | 36 (38.7%) | ||
| Nationality | Saudi | 94 (96.9%) | 77 (82.8%) | 0.001 |
| Non-Saudi | 3 (3.1%) | 16 (17.2%) | ||
| Age | < 20 | 8 (8.2%) | 9 (9.7%) | 0.04 |
| 21 - 40 | 63 (64.9%) | 56 (60.2%) | ||
| 41 - 60 | 20 (20.6%) | 11 (11.8%) | ||
| > 60 | 6 (6.2%) | 17 (18.3%) | ||
Association of clinical characteristics of patients with a new onset of seizures is presented in Table-4. Abnormal CT findings was significantly associated with cases of new onset of seizure (p=0.025). Majority of new cases 69 (74.2%) were taking drugs as compared to known cases 46 (47.4%) (p=0.037). Drug was also detected in new cases by urine analysis 63 (67.7%) (p=0.047). Types of seizure were statistically similar in both groups. Non-compliance to medicine was significantly associated with known cases of seizure (p<0.001), while Intoxication was significantly associated with new onset of seizure (6.5%) (p=0.045). Length of stay was statistically similar in both known and new cases of seizure.
5. DISCUSSION
In our comprehensive study, the distribution of seizure types among the patients displayed a notable pattern: the majority (43.2%) suffered from generalized tonic-clonic seizures, while a smaller fraction experienced Status Epilepticus (4.7%), tonic seizures (3.2%), and focal onset seizures (2.1%). However, a significant percentage (45.3%) fell into the category of unknown seizure types. It is worth noting that within the context of new onset seizures at the Emergency Department of University Hospital, Karachi, Pakistan, generalized tonic-clonic seizures also prevailed as the most prevalent (74.2%) type of seizure, as documented in a study by reference. (8) Another finding emerged from another study, where generalized tonic-clonic seizures constituted the majority (76.6%) of all epileptic seizures. (9) This finding starkly contrasts with the observations made by Maloney et al., where focal seizures were predominant (71%), and generalized seizures were a minority (11%). (10) A community-based study conducted in the eastern province of Saudi Arabia found that among 136 patients, the majority were unclassifiable (51%), 38 patients (28%) showed partial seizure, and 28 patients (21%) demonstrated primary generalized seizure, which shows a lower rate generalized seizure compared to the findings of our study. However, the study included patients under the age of 18 and made a clear distinction between primary and secondary generalized seizure, which is challenging to do in the ER setting. (11)
Evaluating the causes underlying the seizures, non-compliance with prescribed medication surfaced as the primary culprit in 46 cases (24.2%). Structural abnormalities were detected as the etiological factor in 12 cases (6.3%), while the precise cause remained elusive in a significant number of cases, 107 (56.3%). A comparative analysis revealed that non-compliance with medication was significantly associated with known cases of seizure (p<0.001), while intoxication was notably linked with the emergence of new onset seizures (6 cases, 6.5%). A study conducted at Aga Khan University Hospital's Emergency Department delved into the causes of new onset seizures, uncovering structural brain abnormalities as the most prevalent cause, accounting for the majority (49%) of cases. Notably, similar to our study, instances of unattributable causation accounted for a significant proportion (23.6%). (8) Among 695 enrolled patients in another study, acute symptomatic seizures (ASS) were observed in 170 cases (24.5%), primarily triggered by metabolic-toxic abnormalities, with alcohol withdrawal emerging as the most prominent trigger (74.1% of all ASS cases). Additionally, 89.7% of patients exhibited unprovoked seizures, and of these, 377 individuals had a pre-existing epilepsy diagnosis upon presentation to the emergency room. (9). Another study investigating seizure patients' etiology found that among 99 patients with an identified etiology, traumatic brain injury (17.2%) was the most common, followed by other structural causes of epilepsy. (12) A high proportion of traumatic brain injury could be attributed to many patients being young adult males, who are at higher risk of developing a head injury. Consistent with our findings, a study examining compliance with medication revealed that a significant percentage of patients admitted to the ER for seizure were not adherent to AED (26.6%), indicating that non-adherence to medication seems to be a significant contributing factor to ER admission for seizure. (13)
Analyzing radiological findings in our cohort, CT scans revealed abnormal results in 31 cases (16.3%) of the patient cohort. These irregular findings were notably associated with cases of new seizure onset (p=0.025). Correspondingly, an earlier institutional study highlighted that 46% of adults with epilepsy who visited Emergency Departments underwent new imaging, with less than 3% of these cases resulting in acute changes to the management plan. (14) In accordance with our findings, a separate study involving 416 patients with a first seizure concluded that emergent imaging findings on non-contrast imaging were detected in a mere 12% of cases, with acute cerebral bleeding being the prevailing outcome. (15)
Considering hospitalization rates, our study recorded that 37 patients (19.5%) were admitted to the hospital, while 153 patients (80.5%) were discharged. Factors such as advanced age, comorbidities, and the occurrence of status epilepticus appeared to elevate the likelihood of hospitalization. Interestingly, our recorded hospital admission rate contrasts with the findings of Anthony Khoo et al., where approximately half of the ED seizure presentations led to hospital admission. Specific parameters, including a pre-existing seizure disorder, a higher frequency of suspected seizures within the preceding 24 hours, and arrival at the hospital via ambulance, contributed to a higher probability of admission. (16)
When analyzing laboratory parameters, our study did not reveal any statistically significant differences between cases of new onset and known seizures. While direct comparisons between new onset and recurrent seizure cases remain scarce, distinct analyses have explored lab values for each case category independently. In one study, pathology tests among nontraumatic recurrent seizure cases unveiled an abnormality rate of 18.3% (517/2831). Furthermore, 57.7% (56/97) of patients exhibited abnormal antiepileptic drug (AED) levels, a figure exceeding our study's finding of 47.4%, which could be attributed to the study's focus solely on nontraumatic patients. (17) Consistent with our findings, investigations into known seizure cases echoed outcomes observed in new onset seizure patients. In either scenario, laboratory testing demonstrated limited diagnostic value, primarily serving to elucidate the underlying etiology of the seizures. (17-19) Additionally, our study failed to find an association with creatine kinase and seizures, which have long been established to have a positive correlation in most instances. (19) This elevation usually occurs due to strenuous muscle contraction that occurs during seizures. (20)
In a notable trend, the duration of stay within the Emergency Department (ED) was largely consistent for both known and new cases. The majority of patients experienced stays falling within the under 5-hour bracket, followed by durations spanning from 6 to 10 hours, and finally, those exceeding 11 hours. Our analysis underscored a distinct finding: no statistically significant correlation emerged between the length of hospital stay and the differentiation between established cases of epilepsy and newly presented seizures. This observation may come from the implementation of a standardized protocol for managing such cases within our hospital setting. Moreover, it's worth highlighting that the patient profiles in both these cohorts exhibited high similarity, thereby possibly fostering comparable treatment plans. In the context of our study, the mean length of stay (LOS) was computed at 5.93 (±3.4) hours. A similar investigation involving 365 patients yielded noteworthy insights, indicating an average LOS spanning from 45 minutes to 16 hours (21).
Even though our study has yielded valuable insight into the epidemiology of seizures in our region along with their correlation with certain laboratory investigations and clinical imaging, certain limitations should be taken into consideration. The retrospective cross-sectional design, centered within a single tertiary center, hampers our ability to establish causal relationships and temporal sequences. Reliance on medical records introduces potential biases and missing data. Our focus on patients presenting with seizures as their chief complaint within a specific timeframe may exclude cases with different profiles. Additionally, our retrospective approach limits the establishment of temporal relationships between factors and seizure outcomes and the inclusion of other factors such as treatment plan could have added to the benefit of this study.
Table-5. Association of Clinical Characteristics of patients with a new onset of seizures (n=190).
| Seizure | P-Values | |||
|---|---|---|---|---|
| Known Cases | New Onset | |||
| CT Head Done | Yes | 47 (48.5%) | 54 (58.1%) | 0.184 |
| No | 50 (51.5%) | 39 (41.9%) | ||
| CT Findings | Normal | 33 (70.2%) | 37 (68.5%) | 0.03 |
| Abnormal | 14 (29.8%) | 17 (31.5%) | ||
| Blood toxicology screen | Detected | 46 (47.4%) | 69 (74.2%) | 0.037 |
| Not Detected | 51 (52.6%) | 24 (25.8%) | ||
| Urine analysis for drugs | Detected | 52 (53.6%) | 63 (67.7%) | 0.047 |
| Not Detected | 45 (46.4%) | 30 (32.3%) | ||
| Types of Seizure | Generalized Tonic-Clonic | 48 (49.5%) | 34 (36.6%) | 0.07 |
| Status Epilepticus | 5 (5.2%) | 4 (4.3%) | 0.77 | |
| Tonic | 2 (2.1%) | 4 (4.3%) | 0.388 | |
| Focal | 1 (1%) | 3 (3.2%) | 0.28 | |
| Clonic | 2 (2.1%) | 0 (0%) | 0.16 | |
| Post Traumatic | 0 (0%) | 1 (1.1%) | 0.3 | |
| Unknown | 39 (40.2%) | 47 (50.5%) | 0.155 | |
| Cause of Seizure | Non-Compliance to medicine | 40 (41.2%) | 0 (0%) | <0.001 |
| Structural | 3 (3.1%) | 9 (9.7%) | 0.06 | |
| Intoxication | 1 (1%) | 6 (6.5%) | 0.045 | |
| Metabolic | 3 (3.1%) | 4 (4.3%) | 0.66 | |
| Infections | 1 (1%) | 4 (4.3%) | 0.155 | |
| Psychogenic | 2 (2.1%) | 1 (1.1%) | 0.58 | |
| Others | 0 (0%) | 3 (3.2%) | 0.07 | |
| Unknown | 47 (48.5%) | 60 (64.5%) | 0.026 | |
| Length of Stay in ED Hours |
≤ 5 | 45 (46.4%) | 48 (51.6%) | 0.47 |
| >5 - 10 | 38 (39.2%) | 34 (36.6%) | 0.71 | |
| > 10 | 14 (14.4%) | 11 (11.8%) | 0.6 | |
6. CONCLUSION
In summary, our study provides valuable insights into seizure cases within the Emergency Department. Our diverse patient population, comprising both known and new onset cases, revealed demographic similarities, with no significant gender differences. Notably, the majority fell within the 21-40 age group (62.6%), and Saudi nationals constituted the majority (90%) of patients. Generalized tonic-clonic seizures prevailed at 43.2%. The average length of stay was 5.93 hours, and the distribution of new vs. known cases was nearly equal among the 190 patients. Laboratory findings showed no significant associations with either group, mostly falling within the normal range. To optimize care further, we recommend continued refinement of protocols, emphasis on medication compliance, and further research into factors influencing seizure presentations, ensuring tailored approaches in the dynamic realm of emergency care.
Author's contributions:
The all authors were involved in preparation of this article. Final proofreading was made by the first author
Conflict of interest:
The authors declare that research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funding:
There is no any funding for the systematic review and meta-analysis.
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