Incidence and Predictors of Post Stroke Seizure among Adult Stroke Patients in Western Amhara Region, Ethiopia, 2021: A Retrospective Follow up Study

doi:10.21203/rs.3.rs-1975834/v1

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Incidence and Predictors of Post Stroke Seizure among Adult Stroke Patients in Western Amhara Region, Ethiopia, 2021: A Retrospective Follow up Study

https://doi.org/10.21203/rs.3.rs-1975834/v1

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published 25 Jan, 2023

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Background

A seizure is an episode of neurological dysfunction caused by abnormal neuronal activity. Post stroke seizure affects patients’ lives and increase mortality in patients with stroke. It also negatively affects the prognosis of stroke. However, literatures on the occurrence of post-stroke seizure are scanty in Ethiopia. Therefore, this study aimed to assess the incidence and predictors of post-stroke seizure in west Amhara Region, Ethiopia, 2021.

Methods

An institution-based retrospective follow-up study was conducted at western Amhara region from September 20/2021, to October 10 / 2021. Patients who included in this study were come from western Amhara region and that admitted at Felege Hiwot compressive specialized hospital stroke care center. Charts of 568 stroke patients were reviewed through a simple random sampling technique. Descriptive statistics and log-binomial regressions model were applied.

Result

The cumulative incidence and incidence density rate of seizure were 22.18% and 37/1000 persons per day observation respectively. Older age group (ARR = 2.49, 95% CI 1.33–4.69), haemorrhagic stroke (ARR = 1.99, 95% CI 1.25–3.17), Surgical intervention (ARR = 1.85, 95% CI 1.22–2.81) and tramadol medication (ARR = 1.85, 95% CI 1.22–2.81) were found as the significant risk factors of post stroke seizure.

Conclusion

This study found that older age, hemorrhagic type of stroke, surgical management and use of Tramadol anti-pain medication were found as risk factors that increase the risk of post-stroke seizure. Thus, health care professionals shall give special attention and clinical care accordingly for patients with risk factors of post-stroke seizure.

Incidence

predictors

Stroke

Seizure

Bahir Dar

Ethiopia

Stroke is a known neurological disorder and a major cause of symptomatic seizures among older adults(1, 2). It is estimated that between five and fifteen percent of stroke patients develop seizures within two years of stroke onset(3, 4). The pathogenesis of early post-stroke seizures (PSS) following an ischemic stroke is putatively linked to a lowering of seizure threshold secondary to local ionic shifts, the release of excitotoxic neurotransmitters and the presence of global hypo-perfusion with cortical hyper excitability(4, 5).

A seizure is an episode of neurologic dysfunction caused by abnormal neuronal activity that results in a sudden change in behavior, sensory perception, or motor activity. The clinical spectrum of seizures includes simple and complex focal or partial seizures and generalized seizures(6). Seizures may be either provoked or unprovoked. Provoked seizures, also known as acute symptomatic seizures, may result from electrolyte disturbances, Acute toxic effects (antidepressants, sympathomimetic, others), Sepsis, CNS infections, Traumatic brain injury, and Stroke ischemic or hemorrhagic (6–8).

Post-stroke seizure is defined as seizure that occur after a stroke without a previous history of epilepsy(9). Seizure after stroke or post stroke seizure (PSS) is a common and very important complication of stroke. It can be divided into early seizure and late seizure, depending on seizure onset time after the stroke. Early seizure occurring within 1 week of the stroke event and late seizure occurring after 7 days of stroke (10). Most seizures following stroke are focal at onset, but secondary generalization is common, particularly in patients with late-onset seizures(9, 11).

The onset of post-stroke seizures is associated with a series of complex factors, including the type of stroke (ischemic or hemorrhagic), the location and size of the lesion, the severity of the disease. Moreover, studies have revealed High National institutes of health stroke scale score (NIHSS), a significant cortical involvement, hypertension, sex, and alcoholism are associated with an increased risk of developing seizures(12–14).

Post stroke seizure affects patients’ lives and increase mortality in patients with stroke(12). It also negatively affects the prognosis of stroke, including the length of stay, disability rate, quality of life, as well as the physical and mental health of those patients in addition to the burdens of in-hospital costs(14–16). Evidence shows that post-stroke seizure is a common problem(17, 18). Globally, 9% of stroke patients develop seizure(19). In Africa, seizure after stroke varied considerably in different studies ranging from (9.3–14.9%)(4, 16, 20). A study done in Ethiopia showed that about 25% of stroke patients developed post-stroke seizure(21). Sub-Saharan Africa is now a day at the epicenter of a stroke epidemic, which is characterized by a younger age of onset and very poor short and long-term outcomes or consequences from mortality and post-stroke morbidity(4, 5).

More accurate knowledge on risk factors for post stroke seizure after the onset of seizure may have an impact on improving the prevention and treatment of post stroke seizure(12). Post-stroke seizures are associated with longer hospitalization and increased mortality; therefore, prevention and timely treatment of seizures are important (22). Nevertheless, literature on the occurrence of seizure among stroke patients is scanty in Ethiopia in general; we can fairly say that the incidence and its predictors are not well established. Therefore, this study assessed the incidence and predictors of post-stroke seizure.

Study design and period

Institution-based retrospective follow-up study design was conducted from September 20/2021, to October 10 / 2021.

Study area

This study was conducted at the west Amhara region level, patients who admitted with stroke at Felege Hiwot comprehensive specialized Hospital (FCSH) stroke care center, Ethiopia, 2021. The hospital provides services for the people in Amhara and neighboring regions, and it serves over 12 million people from the surrounding area. It is a referral hospital with more than 400 hospital beds and a 95.5% bed occupancy rate (BOR). All hospitals in the region refer stroke patients to FCSH for better diagnostic and management care.

Source population

All stroke patients in west Amhara region

Study population

All stroke patients in west Amhara region who were admitted at FCSH from July/2017 to June/2021.

Inclusion and exclusion criteria

All stroke patients in west Amhara region who were admitted at FCSH from July/2017 to June/2021 were included in the study, whereas patients who had seizure before admission were excluded.

Sample size determination and sampling procedure

The sample size was calculated using Epi-info version-7.2. The total sample size was determined using the double population-proportion formula with the assumption of a 95% confidence level, 80% power, and 1:1 ratio of unexposed to exposed group. The final sample size was calculated using the variable nasogastric tube therapy from the previous study (percent of outcome in unexposed group = 16.5%, percent of outcome in exposed group = 25.5%, and Adjusted Risk ratio = 1.61 then the final sample size was 568).

Initially, medical registration numbers of stroke patients who were admitted from July/2017 to June/2021 at FCSH stroke care center were collected. Then, the patient charts were selected using a computer-generated random sampling technique.

Operational definition

Post-stroke seizure: seizure is an episode of neurologic dysfunction caused by abnormal neuronal activity that occurs after a stroke without a previous history of epilepsy and confirmed by physician.

Stroke: It is sudden brain cell death due to lack of oxygen; the cause is vascular origin, and clinical presentations persist for more than 24 hours.

Comorbidity diseases: A patient who had any disease in addition to stroke.

Data collection tool and procedure

The data were collected using a structured checklist. It comprised different parts, including socio-demographic variables, clinical variables, treatment-related variables, and characteristics of Seizure. The data were collected from existing medical records of the stroke patients from July/2017 to June/2021, and a review of the record was done from September 20/2021, to October 10/ 2021.

Data quality assurance

For the data quality assurance, a proper data extraction checklist was prepared. Before the actual data collection period, the consistency between the data extraction checklist and completeness of the recording system was checked using 5% of the sample size (28 charts). One-day training was given for the data collectors and supervisors. Finally, all the collected data were checked by the investigators for their completeness and consistency during the data entry, storage, management and analysis processes.

Data management and analysis procedure

The completeness and consistency of the checklist were checked manually. Epi data version 3.1 was used to enter the data, and then it was exported to stata version-15 Statistical software for final analysis. Before analysis, missing values were checked by the principal investigators. Missing values were handled through multiple imputation technique. Multicollinearity was checked between independent variables through the variance inflation factor for continuous independent variables and spearman's rank correlation for categorical independent variables.

Hosmer and Lemeshow's test was used to test the model goodness of fit, and its value was 0.80. To assess the association between outcome and independent variables log-binomial regression model was applied at 95% confidence level. To select significant predictors, bi-variable and multi-variable log-binomial regression was carried out. Those variables with a p-value less than 0.25 in the bi-variable analysis were entered into multi-variable analysis. In multi-variable analysis, a P-value of less than 0.05 at 95% confidence interval was taken as a cut point to declare a statistically significant association between predictors and post-stroke Seizure.

Socio-demographic characteristics

In this study, 568 charts of adult stroke patients were reviewed. Of those, 342(60.21%) were males, and the rest, 226 (39.79%) were females. The median age of the patients was 65 years, and the range was 23 - 115 years. Majority of patients, 407 (71.65%), were from rural area (Table-1).

Table-1 Socio-demographic characteristics of patients with stroke at FCSH, Western Amhara region, Ethiopia, 2021 (N=568)

Variables	Categories	Frequency	Percent
Sex	Female	226	39.79
Sex	Male	342	60.21
Age	23 – 44	133	23.42
	45 – 64	127	22.36
	65 – 115	308	54.23
Residence	Urban	161	28.35
Residence	Rural	407	71.65

Clinical characteristics

Among 568 patients, 247(43.49%) had Glasgow coma scale of greater than twelve, and 483 (85.04%) patients had unilateral stroke attack. The predominant stroke type was ischemic, 367 (64.61%), followed by hemorrhagic, 201(35.39%). Half of the patients had at least one chronic disease like hypertension 300 (52.82%), heart diseases 94 (16.15%), diabetes mellitus 61 (10.74%), GERD 229 (40.32 %) and Dysphagia 244(42.96%) (Table-2).

Table-2 Clinical characteristics of patients with stroke at FCSH, Western Amhara region, Ethiopia, 2021 (N = 568)

Variables	Categories	Frequency	Percent

GCS level	≤8	144	25.35
	9 – 12	177	31.16
	>12	247	43.49
Stroked body part Stroked body part	Bilateral	85	14.96
Stroked body part Stroked body part	Unilateral	483	85.04
Type of stroke	Ischemic	367	64.61
Type of stroke	Hemorrhagic	201	35.39
Hypertension	No	268	47.18
Hypertension	Yes	300	52.82
Heart diseases	No	474	83.45
Heart diseases	Yes	94	16.15
Diabetes mellitus	No	507	89.26
Diabetes mellitus	Yes	61	10.74
GERD	No	339	59.68
GERD	Yes	229	40.32
Dysphagia	No	324	57.04
Dysphagia	Yes	244	42.96

Treatment-related characteristics

The majority of the patients were treated by non-surgical treatments (medication therapy) 543 (95.59%), and only 25 (4.41%) were treated with surgery. Among anti-pain medication therapies, Tramadol were the most administered one that accounted 322 (56.69%). Less than one third of participants 176(30.99 %) received oxygen therapy during the study period. Regarding the length of hospital stay, 397 (69.89%) patients spent three up to seven days, and 171 (30.11%) patients spent eight up to twenty-nine days (Table-3).

Table-3 Treatment-related characteristics of patients with stroke at FCSH, Western Amhara region, Ethiopia, 2021 (N = 568)

Variables	Categories	Frequency	Percent
Surgical intervention	No	543	95.59
Surgical intervention	Yes	25	4.41
Mannitol	No	404	71.13
Mannitol	Yes	164	28.87
Tramadol	No	246	43.31
Tramadol	Yes	322	56.69
Metoclopramide	No	428	75.35
Metoclopramide	Yes	140	24.65
Nasogastric tube insertion	No	312	54.93
Nasogastric tube insertion	Yes	256	45.07
Oxygen administered	No	392	69.01
Oxygen administered	Yes	176	30.99
Intravenous fluid therapy	No	383	67.43
Intravenous fluid therapy	Yes	185	32.57
Length of hospital stay	3-7	397	69.89
Length of hospital stay	8-29	171	30.11

Incidence of Post stroke Seizure

The cumulative incidence (CI) and incidence density rate (IDR) of seizure were 22.18% (95% CI 18.83% - 25.83%) and 37/1000 persons per day observation (95% CI 31/1000 – 44/1000), respectively.

Predictors of Seizure

Those variables with a p-value less than 0.25 on bi-variable log-binomial regression analysis were entered into multi-variable log-binomial regression analysis. In multi-variable log-binomial regression, four variables were significantly associated with the development of post-stroke Seizure (age, type of stroke, surgical intervention and tramadol treatment).

In this study, the risk of developing post-stroke Seizure was 1.98 times higher in patients with a age group 45-64 as compared to patients with age group 15-44 (ARR = 1.98, 95 percent CI 1.06—3.70). whereas the risk of developing post-stroke Seizure was 2.49 times higher in patients with a age group 65-115 as compared to patients with age group 15-44 (ARR = 2.49, 95 percent CI 1.33-4.69).

Patients with hemorrhagic stroke were 1.99 times more risk to develop seizure than those with ischemic stroke (ARR = 1.99, 95 percent CI 1.25-3.17). Patients who were managed by surgical intervention were 1.85 times more risk to acquire post stroke seizure than those not managed by surgical intervention (ARR = 1.85, 95 percent CI 1.22-2.81). Patients who were received tramadol medication anti-pain were 3.06 times more likely to acquire post stroke seizure than those not received tramadol medication for anti-pain (ARR = 1.85, 95 percent CI 1.22-2.81).

Table-4 Bi-variable and multi-variable log-binomial regression analysis to the predictors of dysphagia among hospital admitted adult stroke patients at FCSH, Western Amhara region, Ethiopia, 2021

Variables	Category	Seizure		CRR	ARR(95% CI)	P-value
Variables	Category	Yes	No	CRR	ARR(95% CI)	P-value
Sex	Female	52	174	1	-	-
Sex	Male	74	268	0.94	-	-
Age categorized	23-44	25	108	1	1
	45-64	32	95	1.34	1.98(1.06-3.70)	0.032
	65-115	69	239	1.19	2.49(1.33-4.69)	0.005
Residence	Urban	46	115	1	1
Residence	Rural	80	327	0.69	0.64(0.46-1.90)	0.073
GCS level	≤8	43	101	1	1
	9-12	42	135	0.79	1.54(0.94-2.54)	0.089
	>12	41	206	0.56	0.89(0.60-1.32)	0.558
Stroked body part	Bilateral	35	50	1	1
Stroked body part	Unilateral	91	392	0.46	0.80(0.46-1.42)	0.455
Type of stroke	Ischemic	50	317	1	1
Type of stroke	Hemorrhagic	76	125	2.78	1.99(1.25-3.17)	0.004
Hypertension	No	52	216	1	1
Hypertension	Yes	74	226	1.27	0.90(0.61-1.32)	0.577
Heart diseases	No	101	373	1	-	-
Heart diseases	Yes	25	69	1.25	-	-
Diabetes mellitus	No	106	401	1	1
Diabetes mellitus	Yes	20	41	1.57	1.00(0.62-1.61)	0.989
GERD	No	22	317	1	1
GERD	Yes	104	125	6.99	4.35(0.54-5.47)	0.764
Dysphagia	No	31	293	1	1
Dysphagia	Yes	95	149	4.07	2.94(0.99-4.34)	0.071
Surgical intervention	No	108	403	1	1
Surgical intervention	Yes	18	39	1.49	1.85(1.22-2.81)	0.012
Mannitol	No	70	334	1	1
Mannitol	Yes	56	108	1.97	0.94(0.54-1.63)	0.828
Tramadol	No	11	235	1	1
Tramadol	Yes	115	207	7.99	3.01(1.96-4.61)	< 0.001
Metoclopramide	No	99	329	1	-	-
Metoclopramide	Yes	27	113	0.83	-	-
Naso-gastric tube	No	89	223	1	1
Naso-gastric tube	Yes	37	219	0.51	0.16(0.09-1.27)	0.061
Oxygen-therapy	No	84	308	1	-	-
Oxygen-therapy	Yes	42	134	1.11	-	-
Intravenous fluid therapy	No	83	300	1	-	-
Intravenous fluid therapy	Yes	43	142	1.07	-	-
Length of hospital stay	3-7	76	321	1	1
Length of hospital stay	8-29	50	121	1.53	1.47(0.94-2.31)	0.092

ARR= Adjusted Risk Ratio, CI = Confidence Interval, CRR = Crude Risk Ratio, GCS = Glasgow coma scale

The current study assessed the incidence and predictors of post-stroke seizure at western Amhara region. The cumulative incidence (CI) and incidence density rate (IDR) of post stroke seizure were 22.18% (95% CI 18.83% − 25.83%) and 37/1000 persons per day observation (95% CI 31/1000–44/1000), respectively. This cumulative incidence finding was comparable with study conducted in Addis Abeba (25%)(23). In contrast, the incidence of this study was higher than the study conducted in the Ghana (11.4%),(13) Italy (2.3%),(24) Singapore (6.64%),(11) and west Africa (14.9%) (5). The possible reasons for the difference in these studies might be due to different post-stroke patient care and diagnosis approaches to post-stroke seizure.

In this study, the risk of developing post-stroke seizure was 1.98 times higher in patients with an age group 45–64 as compared to patients with age group 15–44. And also the risk of developing post-stroke seizure was 2.49 times higher in patients with an age group 65–115 as compared to patients with age group 15–44. This finding is similar with the study conducted in Japan and West Africa(25, 26). This is due to the reason that old age stage is a peak period for developing epilepsy and seizures.

However, new-onset seizure in the elderly is mainly the consequence of accumulated injuries to the brain and other secondary factors(27). Moreover, Physiological upset is common in older people and could result in acute symptomatic seizures, defined as seizures presenting in close temporal association with a brain insult. On top of that, several medications commonly prescribed to older people are associated with hypernatremia, which can increase seizure risk. Excessive use of alcohol and use of recreational drugs is also another risk factor(28).

Patients with hemorrhagic type of stroke were 1.99 times more risk to develop seizure than those with ischemic stroke. This finding is in line with the studies conducted in Egypt, Sudan and India (4, 25, 29). This is the reason that patients with hemorrhagic type stroke, especially lesions involving the cerebral cortex, are more susceptible to develop seizure after stroke. Furthermore, lesions with venous injury are more likely to present as seizure because venous injury may influence the cortex(27). Seizures after intracerebral hemorrhage may arise due to mechanical effects of the expanding hemorrhage of the cortex due to products of blood metabolism acutely and from hemosiderin depositions and gliotic scarring chronically(22).

Patients who were managed by surgical intervention were 1.85 times more risk to acquired post stroke seizure than those not managed by surgical intervention. This is in line with the studies conducted in Singapore and Saud Arabia (30). This is due to the cause of seizures following surgery is a lack of oxygen reaching the brain, a condition called hypoxia. Moreover Dialysis and brain damage predict seizures after surgery(31). As cerebral vascular occlusion completely obliterates oxygen delivery to the brain, the use of supplemental oxygen, even when not hypoxic, would seem a reasonable solution to try and correct the oxygen deficit(32).

Patients who were received tramadol medication anti-pain were 3.06 times more risk to acquire post stroke seizure than those not received tramadol medication for anti-pain. This finding was similar to studies conducted in USA and Europe(33, 34). this is due to tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile and two such adverse events are serotonin syndrome and seizures(35).

LIMITATION OF THE STUDY

Since the data was gathered from a secondary source, certain essential variables such as patient position status and behavioral variables, which could be predictors of post-stroke seizure, were missed.

This study aimed to determine the incidence and predictors of post-stroke seizure. The cumulative incidence (CI) and incidence density rate (IDR) of post stroke seizure were 22.18% (95% CI 18.83% − 25.83%) and 37/1000 persons per day observation (95% CI 31/1000–44/1000), respectively. Older age, hemorrhagic type of stroke, surgical management of stroke and use tramadol as anti-pain were found as risk factors that increase the risk of post-stroke seizure. The findings of this study would help the healthcare professionals by providing information regarding to predictors of post-stroke seizure for the prevention and the treatment approaches. Thus, health care professionals shall give special attention and clinical care accordingly for patients with risk factors of post-stroke seizure.

ARR -------------------------- Adjusted Risk Ratio

CI ------------------------------ Cumulative Incidence

CRR -------------------------- Crude Risk Ratio

DM --------------------------- Diabetes Mellitus

FCSHF…………………… Felege Hiwot Comprehensive Specialized Hospital

IDR ---------------------------- Incidence Density Rate

GCS ---------------------------- Glasgow Coma Scale

LOHS ------------------------ Length of Hospital Stay

MRN --------------------------- Medical Registration Number

NGT ----------------------------- Nasogastric Tube

PI ------------------------------- Principal Investigator

OPD --------------------------- Out Patient Department

USA ---------------------------- United States of America

Ethical approval and consent

The ethical approval was obtained from the institutional review board of Bahir Dar University, college of medicine and health science. Informed consent was taken from FCSH to review the patient’s medical records. Patient identification numbers and their names were removed for their confidentiality. The data was only used for the study, not for other purposes. This study was conducted following the ethical standard of the declaration of Helsinki.

Consent for publication

Not applicable

Availability of the data

The data used to support the findings of this study are available from one of the corresponding authors on reasonable request.

Competing interest

The authors declare that there is no competing interest.

Funding

The funding source for the current research is from Bahir Dar University College of medicine and health science. The funder had no role in the data collection, analysis, drafting, manuscript, preparation, and publication of this paper.

Author information

Affiliation

Department of Adult Health, College of medicine and health science, Bahir Dar University, Bahir Dar, Ethiopia

Tadios Lidetu, Dagmawit Zewdu

Contributions

Tadios Lidetu ([email protected]) and Dagmawit Zewdu ([email protected]) have equal contribution on organized the original investigation; coordinated the collection of data; analysis and writing the report, supervision in the design of the study and statistical analyses and drafted and revision of the Manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondent: Tadios Lidetu ([email protected])

Acknowledgment

We want to thank Bahir Dar University for the opportunity and financial aid. We would like to extend our sincere thanks to the employees of FCSH (research coordinator, medical ward coordinator, card room workers, and others) for their help during the data collection for this thesis.

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No competing interests reported.

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Reviewers invited by journal
09 Sep, 2022
Editor assigned by journal
09 Sep, 2022
Editor invited by journal
09 Sep, 2022
Submission checks completed at journal
09 Sep, 2022
First submitted to journal
18 Aug, 2022

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Incidence and Predictors of Post Stroke Seizure among Adult Stroke Patients in Western Amhara Region, Ethiopia, 2021: A Retrospective Follow up Study

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Result

Conclusion

Introduction

Methods & Materials

Results

Socio-demographic characteristics

Clinical characteristics

Treatment-related characteristics

Incidence of Post stroke Seizure

Predictors of Seizure

Discussion

LIMITATION OF THE STUDY

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1