RESEARCH ON CLINICAL, PARACLINICAL CHARACTERISTICS AND RISK FACTORS FOR EPILEPSY IN PATIENTS AFTER SUPRATENTORIAL STROKE

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES --- --- LE DINH AN RESEARCH ON CLINICAL, PARACLINICAL CHARACTERISTI

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

- -

LE DINH AN

RESEARCH ON CLINICAL, PARACLINICAL

CHARACTERISTICS AND RISK FACTORS FOR EPILEPSY

IN PATIENTS AFTER SUPRATENTORIAL STROKE

Speciality: Neuroscience Code: 9720158

ABSTRACT OF MEDICAL PHD THESIS

Hanoi – 2024

THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

Supervisor:

1 Dr Nguyen Hong Quan

2 Dr Ngo Tien Tuan

Reviewer:

This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences

Day Month Year

The thesis can be found at:

1 National Library of Vietnam

2 Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences

3 Central Institute for Medical Science Infomation and Tecnology

1

INTRODUCTION

Stroke is one of the most common causes of epilepsy, accounting for 10% of all epilepsy causes Post-stroke seizure (PSS) increases the risk of death, reduces quality of life, and reduces the ability to recover function after a stroke Prolonged treatment with antiepileptic drugs also increases the risk of recurrent stroke

According to some studies, the incidence of epilepsy after stroke is about 2.5-17% depending on the study Most studies show that damage

to the supratentorial region, especially the cerebral cortex, is a risk factor for PSS, as well as a number of other factors such as intracranial hemorrhage and hemorrhagic transformation in cerebral infarction , severe stroke level also increases the risk of post-stroke epilepsy

In Vietnam, there are a number of studies describing the characteristics of seizure after stroke, mainly studying late seizures There are currently no studies on early seizures or identifying risk factors for seizure after supratentorial stroke, so we conducted this topic with the research goal:

1 Describe clinical and paraclinical characteristics and prognosis

of seizures in patients after supratentorial stroke

2 Analyze risk factors for PSS in this patient group

CHAPTER 1 OVERVIEW 1.1 Seizure and diagnosis of seizure after stroke

+ Seizure ( seizure ) is defined as “a transient event of signs and/or

symptoms due to abnormally excessive or synchronized brain activity”

+ Epilepsy is a chronic disease process characterized by recurrent

2 unprovoked seizures

In 2014, the International League Against Epilepsy issued

diagnostic criteria to define epilepsy, that is a chronic disease

characterized by at least one of the following criteria:

- When there are at least 2 unprovoked seizures occurring more than 24 hours apart, not related to any acute brain injury or metabolic disorder

- When an unprovoked seizure occurs and the risk of recurrence after a second seizure occurring within the next 10 years is at least 60% (for causes including traumatic brain injury with intracranial lesions, after brain surgery, stroke, etc.)

- Diagnosed epilepsy syndrome

+ Post-stroke epilepsy ( PPE)

PSS is divided into two types based on the time of onset (Holtkamp, Beghi et al 2017) :

+ Early seizure (ES) is also called acute symptomatic seizure: is a

seizure condition that occurs within 7 days after a stroke The symptoms of ES are often acute, and appear most often within the first

24 hours after a stroke

+ Late seizures or unprovoked seizures ( LS): Seizures occurring

after the 7th day of the stroke According to the 2014 ILAE definition

of seizures, LS are considered to be seizures of remote origin or

unprovoked seizures and are also called Post Stroke Epilepsy

1.1.2 Pathology

Currently, the main widely accepted hypotheses for the mechanism

of ES include: damage to the blood -brain barrier (BBB), ion channel dysfunction , neurotransmitter imbalance, elevated serum cortisol levels, hemosiderin deposition

Brain lesions in LS are more long-term than the transient lesions that cause ES Many mechanisms are known to cause LS such as

3 chronic inflammation, astrocytic proliferation, structural changes in the brain cell network, angiogenesis, axonal degeneration, new synapse formation, altered synaptic plasticity or regional hemodynamic changes, and genetic disorders

1.2 Clinical, paraclinical and prognosis of PSS

1.2.1 Clinical

The frequency of the types of seizure does not differ much between

ES and LS, with focal seizures predominating (including focal with/without cognitive deficits, and bilateral secondary generalized seizures) Clinical studies of epilepsy after stroke show that signs of focal motor seizures are recorded earliest In terms of frequency, focal

to bilateral tonic-clonic seizures are recorded most often; followed by focal seizures with or without absence of consciousness

1.2.2 Paraclinical

Electroencephalography (EEG) is a medical imaging technique of supporting the clinical diagnosis of neurological disorders, especially for seizure patient Routine EEG is indicated to diagnose epilepsy and may assist in selecting treatment options with antiepileptic drugs Studies on EEG in ES show that abnormal signs on EEG are mainly: (1) slow activity (localized or general), (2) periodic discharge and (3) epileptiform activity on EEG

Besides, some imaging diagnostic tools such as MRI/CT perfusion also play a certain role Signs such as increased perfusion or no visible lesion on DWI pulse help distinguish PSS and post-stroke lesions

1.2.3 Prognosis of PSS

Many studies around the world show that both ES and LS have negative effects on the recovery ability, quality of life and mortality rate of patients after stroke

Gender, and factors such as smoking and alcohol abuse are often included in the analysis, however results from studies are inconsistent, and data from meta-analyses have not shown the impact of these factors

Among the factors of medical history and comorbidities: hypertension, diabetes, arrhythmia, lipid disorders are often mentioned Hypertension has been evaluated by more studies To date, studies have not yet reached a consensus on the impact of these factors

on the risk of ES

Characteristics of stroke lesions have been evaluated by many studies In which, the severity of stroke, lesions related to the cerebral cortex, cerebral hemorrhage, and extensive lesions are thought to increase the risk of stroke

1.3.2 Late seizures

Some studies also show that old age is a risk factor for LS (Chi (2018), Burn (1997) Regarding gender, Roivainen (2013) noted that men have a higher rate of LS Meanwhile, Mehta's study (2018) did not record a clear effect of this factor

Regarding medical history and comorbidities, some studies have noted factors associated with increased risk of LS including: history of arrhythmia (Tanaka -2015), hypertension ( J.Phan -2022), alcohol and tobacco abuse (Conrad-2013), Chen -2022), diabetes, renal failure, electrolyte disturbances (Mehta -2018)

5 Stroke characteristics factors recorded the most significant impact

on LS through studies Galovic (2018) developed a model to predict

LS prognostic factors, showing that cortical lesions were one of the independent prognostic factors, increasing the risk of LS by 4.2 times (p=0.003)

CHAPTER 2 METHODS 2.1 RESEARCH SUBJECTS

Including 1061 patients diagnosed with supratentorial stroke according to WHO standards, examined at the Department of Neurology and Stroke Department, Central Military Hospital 108 from 2018-2022 and Stroke Center, Provincial General Hospital Phu Tho from 2020-2022

2.1.1 Criteria for selecting patients

- Diagnosed with confirmed stroke according to WHO standards

- Over 18 years

- Stroke in the supratentorial region

- Agree to participate in the study

2.1.2 Exclusion criteria

- Patients with a history of seizures or epilepsy

- There is combined cerebellar and brainstem damage, or subarachnoid hemorrhage

- Patients with brain damage due to other causes

- Suffering from serious systemic diseases such as sepsis, cancer, kidney failure, severe metabolic disorders Alcoholism or mental disorders

- Patients who are not followed up or die within 3 months of stroke

2.1.3 Research sample size

Use the sample size calculation formula for cross-sectional, retrospective and prospective descriptive studies with longitudinal follow-up

𝑛 =

𝑍1−𝛼 2

2 𝑃(1 − 𝑃)

ⅆ2

d is the acceptable error level of 0.02

Applying this we get n ≥ 865 patients

2.2 Research Methods

2.2.1 research process

- Select patients who satisfy the selection criteria

- Collect information at the time of admission to the hospital, including: general characteristics, related medical history, lifestyle, clinical and paraclinical characteristics of the PSS and stroke

- Information on recovery, mortality, and characteristics of seizure at the time of discharge for all patients ,6 months to 1 year after discharge,

or when there is suspicion of seizure reported by the patient or their families Finish time of research is December 2022

2.2.2 Evaluation and monitoring criteria

- Genaral characteristic: age, gender

- Medical history and comorbidity , including: hypertension, diabetes, cardiovascular disease, lifestyle, history of stroke

- Characteristics of stroke: lesion type, location, size, Glassgow score, NIHSS, mRS, TOAST

- Characteristics of seizures: time, classification, number of seizures, type of seizure

- EEG characteristics: pathological changes outside and during attacks

- Blood test: Complete Blood Count, serum biochemistry, echocardiography, electrocardiography, CT/MRI of the brain

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2.2.3 Research facilities

- Video electroencephalogram from Nippon model EEG 200, NeuroWerk EEG36 Sigma electroencephalogram

- 1.5 or 3 Tesla magnetic resonance machine, 16 slice CT scanner

- Biochemistry and hematology machines are available at Central Military Hospital 108 and Phu Tho Provincial General Hospital

2.2.4 Statistical methods

Data were collected according to the survey form and entered into EpiData Entry software, version 3.1 and processed according to SPSS, 20.0 program

Describe quantiative variables in terms of mean and standard deviation, qualitative variables in terms of proportions Univariate analysis with Chi-square test (qualitative) or T-test (quantitative) Logistic multivariate regression model evaluates factors related to SCD, results are presented as odd-ratio (OR) and 95% confidence interval (95% CI) When there are multiple multivariate models, the model with the lowest AIC score is selected

2.3 Research content

- Clinical, paraclinical and prognostic assessment of PSS

- Evaluate risk factors for PSS

2.4 Research ethics :

The study was approved by the Research Topic Approval Council, according to Decision No 320/QD- V108 dated September 1, 2016, the Board of Directors of Central Military Hospital 108 Research participation is voluntary, personal information has been encrypted and data is only used for this study

2.5 Research diagram

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CHAPTER 3 RESULT 3.1 Clinical, paraclinical, prognosis of PSS

3.1.1 Clinical and paraclinical characteristics of ES

Stroke patient enroll

Supratentorial stroke patient meet

No ES (n=1000) Compare 2 group

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Table 3.1 Distribution of patients with early CDK by type of CDK

Comment : Generalized seizures account for the majority In focal

type, simple partial seizure (seizure without reduced awareness) account for 73.7%

Chart 3.1 Onset date of ES

Comment :

The first day has the highest rate of onset of ES (24.6%)

Table 3.2 Distribution of patients with early seizures according

to patient age and gender

Male 47 (6.6) 661 (93.4) 708 (100)

>0.05 Female 14 (4.0) 339 (96.0) 353 (100)

Age group

<65 32 (4.1) 755 (95.9) 787 (100) < 0.001

2.43 (1.44-4.09)

≥65 29(10.6) 245 (89.4) 274 (100)

Total 61 (5.7) 1000 (94.3) 1061 (100)

𝑋 ̅ ±SD 61.5±12.3 57±10.7 57.4 ± 10.8 <0.05

Comment : There is a significant difference between the age

groups above and below 65

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3.1.1 Clinical and paraclinical characteristics of LS

Chart 3.4 Late seizure onset time Comment : LS appeared in 41/1061 patients with stroke, of

which 17/41 (41.5%) patients had late onset seizures in the first 6 months after stroke and there were 31/41 (75.6%) case appear first LS

in the first year

Table 3.9 Distribution of LS according to seizure type

Type of seizure

Type of attack (n, %) Awareness Impaired

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Table 3.11 Distribution of patients with tardive epilepsy according to

age and sex

Age group

< 65 20 (2.5) 767 (94.9) 787 (100) < 0.01

1.69 (0.89-3.2)

mainly in the left hemisphere, accounting for 57%

32%

57%

11%

Abnormal activities on EEG

Chart 3.9 Abnormal EEG activities location by lobe

Comment : On video EEG or long-term EEG recordings,

temporal and parietal lobe damage is common in 09/41(22%) patients 3.1.3 Prognosis of DKSQ

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Table 3.20 Association between early epilepsy and modified Rankin

scale scores at different time points

After 6 months

to 1 year

mRS < 3 21 519 2.06 (1.19 – 3.54),

< 0.05 mRS ≥ 3 40 481

Time to end

the study

mRS < 3 23 572 1.92 (1.10 – 3.34)

< 0.05 mRS ≥ 3 31 402

Comment: ES increased the rate of slow recovery

Table 3.22 Association between LS and modified Rankin scale

Comment: There was no significant difference in longitudinal

follow-up between groups with and without late seizures

3.2 Risk factors of PSS

3.2.1 Some factors related to ES

Table 3 23 Association of ES and general characteristics

Characteristic Univariate

OR (95% CI), p

Multivariate

OR (95% CI), p Woman 0.97 (0.96 - 1.01), > 0.05 0.55 (0.29 - 1.00), > 0.05 Age: Taller 1.03 (1.01 - 1.04), < 0.01 1.64 (1.16 - 2.33), < 0.01 BMI: Higher 1.14 (0.99 – 1.31), > 0.05 0.71 (0.47 – 1.06), > 0.05

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Comment: Univariate and multivariate analysis of age groups

showed that the older the age, the higher the rate of ES increased by 1.64 times with p < 0.01, statistically significant

Table 3.24 Association of ES with stroke characteristics

Comorbidities Univariate

OR (95% CI), p

Multivariate

OR (95% CI), p Hypertension 1.01 (0.98 - 1.04), >

0.05 0.99 (0.96 - 1.02), > 0.05 Diabetes 1.00 (0.96 - 1.04), >

0.05 0.99 (0.96 - 1.03), > 0.05 Disorders of

blood lipid

metabolism

1.02 (0.95 – 1.11), >

0.05 1.02 (0.96 - 1.10), > 0.05 Heart valve

disease

1.00 (0.90 – 1.11), >

0.05 0.95 (0.84 - 1.06), > 0.05 Heart arrhythmia 1.10 (1.03 – 1.19), <

0.01 1.04 (0.97 - 1.12), > 0.05 Previous stroke 1.27 (1.23 –

1.31),<0.001 1.27(1.22 - 1.31),< 0.001

Comment: Multivariate analysis showed that only the factor of

having a previous stroke was statistically significantly associated with early stroke

Table 3.25 Relationship of ES with Glasgow scale and NIHSS

Characteristic Univariate

OR (95% CI), p

Multivariate

OR (95% CI), p Glasgow decreased

Comment: The lower the Glasgow score, the higher the risk of ES

Specifically, when the Glasgow score decreases by 1 point, O