Incidence and Predictors of Post Stroke Seizure among Adult ...

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Incidence and Predictors of Post Stroke Seizureamong Adult Stroke Patients in Western AmharaRegion, Ethiopia, 2021: A Retrospective Follow upStudyDagmawit Zewdu 

Bahir Dar UniversityTadios Lidetu  ( [email protected] )

Bahir Dar University* 

Research Article

Keywords: Incidence, predictors, Stroke, Seizure, Bahir Dar, Ethiopia

Posted Date: August 19th, 2022

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

License: This work is licensed under a Creative Commons Attribution 4.0 International License.  Read Full License

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Abstract

BackgroundA seizure is an episode of neurological dysfunction caused by abnormal neuronal activity. Post strokeseizure affects patients’ lives and increase mortality in patients with stroke. It also negatively affects theprognosis 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 AmharaRegion, Ethiopia, 2021.

MethodsAn institution-based retrospective follow-up study was conducted at western Amhara region fromSeptember 20/2021, to October 10 / 2021. Patients who included in this study were come from westernAmhara 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. Descriptivestatistics and log-binomial regressions model were applied.

ResultThe cumulative incidence and incidence density rate of seizure were 22.18% and 37/1000 persons per dayobservation 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 signi�cant risk factors of post stroke seizure.

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

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

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

Post-stroke seizure is de�ned 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. Itcan be divided into early seizure and late seizure, depending on seizure onset time after the stroke. Earlyseizure 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 inpatients with late-onset seizures(9, 11).

The onset of post-stroke seizures is associated with a series of complex factors, including the type ofstroke (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 signi�cant corticalinvolvement, hypertension, sex, and alcoholism are associated with an increased risk of developingseizures(12–14).

Post stroke seizure affects patients’ lives and increase mortality in patients with stroke(12). It alsonegatively affects the prognosis of stroke, including the length of stay, disability rate, quality of life, as wellas 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 patientsdevelop 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 ischaracterized by a younger age of onset and very poor short and long-term outcomes or consequencesfrom mortality and post-stroke morbidity(4, 5).

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

Methods & MaterialsStudy design and period

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

Study area 

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

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 wereincluded 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 usingthe double population-proportion formula with the assumption of a 95% con�dence level, 80% power, and1:1 ratio of unexposed to exposed group. The �nal sample size was calculated using thevariable 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 �nal samplesize was 568).

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

Operational de�nition

Post-stroke seizure: seizure is an episode of neurologic dysfunction caused by abnormal neuronalactivity that occurs after a stroke without a previous history of epilepsy and con�rmed by physician.

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

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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. Thedata 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 datacollection period, the consistency between the data extraction checklist and completeness of the recordingsystem was checked using 5% of the sample size (28 charts). One-day training was given for the datacollectors and supervisors. Finally, all the collected data were checked by the investigators for theircompleteness 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 usedto enter the data, and then it was exported to stata version-15 Statistical software for �nal analysis. Beforeanalysis, missing values were checked by the principal investigators. Missing values were handledthrough multiple imputation technique. Multicollinearity was checked between independent variablesthrough the variance in�ation factor for continuous independent variables and spearman's rank correlationfor categorical independent variables. 

Hosmer and Lemeshow's test was used to test the model goodness of �t, and its value was 0.80. Toassess the association between outcome and independent variables log-binomial regression model wasapplied at 95% con�dence level. To select signi�cant predictors, bi-variable and multi-variable log-binomialregression was carried out. Those variables with a p-value less than 0.25 in the bi-variable analysis wereentered into multi-variable analysis. In multi-variable analysis, a P-value of less than 0.05 at 95%con�dence interval was taken as a cut point to declare a statistically signi�cant association betweenpredictors and post-stroke Seizure.

Results

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

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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

Male  342 60.21Age   23 – 44 133 23.42

45 – 64 127 22.3665 – 115 308 54.23 

Residence  Urban  161 28.35 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%), followedby 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 Dysphagia244(42.96%) (Table-2).

Table-2 Clinical characteristics of patients with stroke at FCSH, Western Amhara region

Ethiopia, 2021 (N = 568)

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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

Unilateral  483 85.04

Type of stroke     Ischemic  367 64.61

Hemorrhagic  201 35.39

Hypertension

No  268 47.18

Yes  300 52.82

Heart diseases

No  474 83.45

Yes  94 16.15

Diabetes mellitus No  507 89.26

Yes  61 10.74

GERD No  339 59.68

Yes  229 40.32 

Dysphagia  No  324 57.04 

Yes  244 42.96

Treatment-related characteristicsThe 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 themost 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%)

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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

Yes  25 4.41Mannitol   No  404 71.13 

Yes   164 28.87Tramadol No  246 43.31

Yes  322 56.69Metoclopramide No  428 75.35

Yes  140 24.65Nasogastric tube insertion No  312 54.93 

Yes  256 45.07Oxygen administered  

No  392 69.01Yes  176 30.99

Intravenous fluid therapy 

No  383 67.43 Yes  185 32.57 

Length of hospital stay  3-7 397 69.898-29 171 30.11 

Incidence of Post stroke SeizureThe 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 enteredinto multi-variable log-binomial regression analysis. In multi-variable log-binomial regression, four

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variables were signi�cantly 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 group45-64 as compared to patients with age group 15-44 (ARR = 1.98, 95 percent CI 1.06—3.70). whereas therisk of developing post-stroke Seizure was 2.49 times higher in patients with a age group 65-115 ascompared 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 ischemicstroke (ARR = 1.99, 95 percent CI 1.25-3.17). Patients who were managed by surgical intervention were1.85 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 3.06times 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

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Variables  Category  Seizure  CRR ARR(95% CI) P-value

Yes  No Sex  Female  52 174 1 - -

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) 0.03265-115 69  239 1.19 2.49(1.33-4.69) 0.005

Residence Urban  46  115 1 1  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  Unilateral  91 392 0.46 0.80(0.46-1.42) 0.455

Type of stroke Ischemic  50  317 1 1  Hemorrhagic 76  125 2.78 1.99(1.25-3.17) 0.004

Hypertension No  52  216 1 1  Yes 74  226 1.27 0.90(0.61-1.32) 0.577

Heart diseases  No  101  373 1 - -Yes 25 69 1.25 - -

Diabetes mellitus  No  106  401 1 1  Yes 20 41 1.57 1.00(0.62-1.61) 0.989

GERD No  22 317 1 1  Yes 104  125 6.99 4.35(0.54-5.47) 0.764

Dysphagia  No  31 293 1 1  Yes 95  149 4.07 2.94(0.99-4.34) 0.071

Surgical intervention  No  108 403 1 1  Yes  18  39 1.49 1.85(1.22-2.81) 0.012

Mannitol  No  70  334 1 1  Yes  56  108 1.97 0.94(0.54-1.63) 0.828

Tramadol   No  11 235 1 1  Yes 115  207 7.99 3.01(1.96-4.61) < 0.001

Metoclopramide   No  99 329 1 - -Yes 27  113 0.83 - -

Naso-gastric tube  No  89  223 1 1  Yes 37 219 0.51 0.16(0.09-1.27) 0.061

Oxygen-therapy  No  84  308 1 - -Yes 42  134 1.11 - -

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Intravenous fluid therapy  No  83  300 1 - -Yes 43  142 1.07 - -

Length of hospital stay  3-7 76  321 1 1  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 

DiscussionThe 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% CI18.83% − 25.83%) and 37/1000 persons per day observation (95% CI 31/1000–44/1000), respectively.This cumulative incidence �nding was comparable with study conducted in Addis Abeba (25%)(23). Incontrast, 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 inthese studies might be due to different post-stroke patient care and diagnosis approaches to post-strokeseizure.

In this study, the risk of developing post-stroke seizure was 1.98 times higher in patients with an age group45–64 as compared to patients with age group 15–44. And also the risk of developing post-stroke seizurewas 2.49 times higher in patients with an age group 65–115 as compared to patients with age group 15–44. This �nding is similar with the study conducted in Japan and West Africa(25, 26). This is due to thereason 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 brainand other secondary factors(27). Moreover, Physiological upset is common in older people and couldresult in acute symptomatic seizures, de�ned as seizures presenting in close temporal association with abrain insult. On top of that, several medications commonly prescribed to older people are associated withhypernatremia, which can increase seizure risk. Excessive use of alcohol and use of recreational drugs isalso another risk factor(28).

Patients with hemorrhagic type of stroke were 1.99 times more risk to develop seizure than those withischemic stroke. This �nding 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 cerebralcortex, are more susceptible to develop seizure after stroke. Furthermore, lesions with venous injury aremore likely to present as seizure because venous injury may in�uence the cortex(27). Seizures afterintracerebral hemorrhage may arise due to mechanical effects of the expanding hemorrhage of the cortexdue to products of blood metabolism acutely and from hemosiderin depositions and gliotic scarringchronically(22).

Patients who were managed by surgical intervention were 1.85 times more risk to acquired post strokeseizure than those not managed by surgical intervention. This is in line with the studies conducted in

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Singapore and Saud Arabia (30). This is due to the cause of seizures following surgery is a lack of oxygenreaching the brain, a condition called hypoxia. Moreover Dialysis and brain damage predict seizures aftersurgery(31). As cerebral vascular occlusion completely obliterates oxygen delivery to the brain, the use ofsupplemental oxygen, even when not hypoxic, would seem a reasonable solution to try and correct theoxygen de�cit(32).

Patients who were received tramadol medication anti-pain were 3.06 times more risk to acquire post strokeseizure than those not received tramadol medication for anti-pain. This �nding was similar to studiesconducted in USA and Europe(33, 34). this is due to tramadol's serotonin and norepinephrine reuptakeinhibitory effects result in a unique adverse effect pro�le and two such adverse events are serotoninsyndrome and seizures(35).

LIMITATION OF THE STUDYSince the data was gathered from a secondary source, certain essential variables such as patient positionstatus and behavioral variables, which could be predictors of post-stroke seizure, were missed.

ConclusionThis study aimed to determine the incidence and predictors of post-stroke seizure. The cumulativeincidence (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 asrisk factors that increase the risk of post-stroke seizure. The �ndings of this study would help thehealthcare professionals by providing information regarding to predictors of post-stroke seizure for theprevention and the treatment approaches. Thus, health care professionals shall give special attention andclinical care accordingly for patients with risk factors of post-stroke seizure.

AbbreviationsARR -------------------------- 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

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

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

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

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

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

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

DeclarationsEthical approval and consent  

The ethical approval was obtained from the institutional review board of Bahir Dar University, college ofmedicine and health science. Informed consent was taken from FCSH to review the patient’s medicalrecords. Patient identi�cation numbers and their names were removed for their con�dentiality. The datawas only used for the study, not for other purposes. This study was conducted following the ethicalstandard of the declaration of Helsinki. 

Consent for publication

Not   applicable

Availability of the data 

The data used to support the �ndings of this study are available from one of the corresponding authors onreasonable 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 healthscience. The funder had no role in the data collection, analysis, drafting, manuscript, preparation, andpublication of this paper. 

Author information 

A�liation 

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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]) haveequal contribution on organized the original investigation; coordinated the collection of data; analysis andwriting the report, supervision in the design of the study and statistical analyses and drafted and revisionof the Manuscript. All authors read and approved the �nal manuscript.

Corresponding author

Correspondent: Tadios Lidetu ([email protected])

Acknowledgment 

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

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