MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENSE 108 INSTITUTE O F C LINICAL MEDICAL AND PHARMACEUTICAL SCIENC ES NGUYEN THE ANH STUDY O N CLINICAL AND PARAC LINICAL O F ISCHEMIC S TRO KE IN THE ELDERLY PATIENT WITH DIABETES Speciality: Ne urology Code: 62720147 SUMMARY O F MEDICAL DO CTO RAL THESIS HA NO I - 2018 Re se arch comple te d at: 108 INSTITUTE O F C LINICAL MEDICAL AND PHARMACEUTICAL SCIENC ES Scientific Supervisors: Prof P hD Le Quang Cuong Prof P hD Hoang Van T huan Reviewer 1: Reviewer 2: Reviewer 3: T he doctoral thesis will be defended at the Public Defence At on A t hesis can be found at: Nat ional Library of Vietnam Library of 108 Milit ary Central Hospit al BAC KGRO UND Brain stroke, a fat al and disabling disease which is common among elderly and is an developmental problem Each year there are about 15 million people suffer from stroke, of which million die and ot her million are disabled Ischemic stroke takes about 80-85% of stroke Ischemic stroke (IS) occurs when blood supply to part of the brain are blocked, causing necrosis of the respect ive brain t issue T here are lot s of fact or that lead t o ischemic stroke and diabetes is one of the most common In 2015, there are about 415 million people with diabetes worldwide, 90% of which are type diabetes, and the rat e of diabetes among people aged 60-79 is 25.9% Diabetes increases the risk of atherosclerosis by 2-3 times and doubles the risk of stroke compared with normal people The rate of ischemic stroke in pat ients with diabetes is about 25-40% Patients with diabetes also experience co-occurring risk factors such as atheroma, hyperlipidaemia, hypert ension, which t ogether cause early, severe ischemic stroke and slower recovery In Vietnam, there hasn’t been any study on ischemic stroke that specified in elderly with diabetes Hence our research: “Stu dy on clinical and paraclinical characteristics of ischemic stroke in th e elderly wi th diabete s” T here are two object ive: Research on neurological characteristics, m etabolic syndrom es and magnetic resonance imaging of ischem ic stroke in the elderly with diabetes Consider the association between diabetes and cerebral infarction in the elderly NEW MAIN CO NTRIBUTIO N O F THE THESIS - T his is a prospect ive, descriptive, controlled study which systematized clinical, biochemical and imaging characteristic of ischemic stroke in elderly with diabetes T he results are described in detail, and are compared with patients with non-diabetic ischemic stroke - T he study utilized analytical algorit hms to assess the role of diabetes and related parameters such as blood glucose, HbA1c, NIHSS score, Glasgow scale upon hospit al admission and met abolic syndrome t o t he outcome of ischemic stroke in the elderly O VERALL LAYO UT T his thesis consist of 130 pages including: Background (2 pages), Chapter 1: Lit erature review (35 pages), Chapter 2: Subject s and methods (19 pages), Chapter 3: Results (30 pages) Chapter 4: Discussion (41 pages), Conclusions (2 pages), Recommendations (1 page) T his thesis also consist of 42 tables, 10 graphs, diagram, images, 172 references including 43s in Vietnamese, 129s in English and related art icles *Acronyms: IS-ischemic stroke CHAPTER 1: LITERATURE REVIEW 1.1 Abou t ische mic stroke 1.1.1 De fi niti on and cl assifi cati on of ische mic stroke T he occurrence of IS is the consequence of a sudden decline in cerebral circulation due t o part ial or total cerebral art ery occlusion Clinical manifestations of IS are sudden appearances of focal neurologic signs 1.1.2 Cause s of ische mic stroke According to T OAST ischemic stroke causes can be categorized int o five major group: major vascular disorders, cardiac disorders, small vessel disorders, other causes and unknown causes 1.1.3 Clinical manife stati ons Sudden onset of focal neurologic sign depends on t he size and location of the injured art ery, including hemiparesis, sensory disorders, speech disorders, facial paralysis, convulsions, disorders of consciousness In addition, clinical severity was assessed using t he NIHSS scale, with sequelae assessed using a modified Rankin scale 1.1.4 Imaging diagnosis tools - MRI is a method with high sensitivit y, surpass computerized tomography in t he diagnosis of IS - Other tests also play roles in the diagnosis of IS, such as Doppler ultrasound of ext ernal carotid artery, elect rocardiography, biochemistry t est etc 2.1 Ische mic stroke in e lderly wi th diabete s 2.1.1 Abou t diabete s - Diabetes is a chronic metabolic disorder, with genetic fact ors T he disease is characterized by increased blood glucose T he main cause is absolute or relative insulin deficiency which in t urn leads t o impaired glucose, protein, lipid and minerals met abolism T here are four main types of diabetes: type diabetes, type diabetes and gestational diabetes and other specific t ypes of diabetes - Insulin resistance is a decrease in the biological response to insulin, usually expressed by an increase in insulin levels in the blood Insulin resistance is considered to be one of the primary defect s leading to the onset of type diabetes Insulin resistance is a central factor in metabolic syndrome Met abolic syndrome has six major components: abdominal obesity, atherogenic dyslipidaemia, hypert ension, insulin resistance, proinflammatorystates , - Vascular complication in patient with diabetes Cardiovascular diseases, especially atherosclerosis, are major causes of disability and deat h in people with diabetes It significantly increases the risk of progressive coronary artery disease, cerebrovascular disease and other peripheral arterial diseases 2.1.2 Nati onal and inte rnati onal re se arch e s re late to the sis -Diabetes is one of the leading independent risk factors of IS The risk of stroke in people with diabetes is two t imes higher than that of ordinary people - Age, previous strokes, atrial fibrillation, art erial hypert ension, smoking, dyslipidaemia, hyperglycaemia, durat ion of diabetes are risk fact ors of IS - T he rat e of acute onset of IS, lacunar stroke and stroke due t o cerebrovascular disease was higher in the diabetic group than t hat of the non-diabetic group T he incidence of hippocampal stroke and posterior cerebral art ery stroke is also higher in the diabetic group - T he rat e of first-trimester disability (on t he Rankin and Bart hel scale) of stroke patient was higher in diabetic group than that of nondiabetic group - HbA1c were not associat ed with outcomes of ischemic stroke CHAPTER 2: SUBJECTS AND RESEARC H METHO DS 2.1 Locati on and durati on of th e re se arch - Locat ion: T hanh Nhan Hospit al, Ha Noi - Duration: From November 2011 t o May 2015 2.2 Subje cts Patients aged 60 years and over who were diagnosed with cerebral ischemic stroke (IS) and treated in T hanh Nhan hospit al - Research group: Diabetic stroke patients - Controlled group: Non-diabetic stroke patients 2.2.1 Eligibility cri te ria - Patients aged 60 years and over - Hospit alizat ion within the first 48 hours of symptom onset - Diagnostic criteria for cerebral ischemic stroke (IS) + Clinical crit eria as defined by t he World Healt h Organization (1989): a clinical syndrome consisting of rapidly developing clinical signs of focal (or global in case of coma) disturbance of cerebral funct ion lasting more than 24 hours or leading to deat h with no apparent cause other than a vascular” + Diagnostic Imaging Criteria: MRI was performed within the first 48 hours of symptom onset MRI revealed IS: isointensity or low signal intensity seen at T imaging, high signal int ensity seen at T imaging or FLAIR, restrict ed diffusion on DWI - Diagnostic crit eria for diabetes as defined by American Diabetes Associat ion (ADA) 2010 , are any of the following: + A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with symptoms of hyperglycaemia or hyperglycemic crisis + A fast ing plasma glucose (FP G) level of 126 mg/dL (7 mmol/L) or higher Fasting is defined as no caloric intake for ≥8 hours + A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75g oral glucose tolerance t est (OGT T ) + HbA1c ≥ 6.5% 2.2.2 Exclusion cri te ria - Patients with haemorrhage-ischemic stroke - Patients with IS accompanied by cerebrovascular malformation or brain tumours - Patients were t reated with t hrombolytic therapy - Patients with a history of stroke with sequelae of grade or higher on a modified Rankin scale - Patients with a history of mental disorders and / or traumatic brain 2.3 Re se arch me th od 2.3.1 Research design: Prospective descriptive comparative crosssectional study 2.3.2 Sample Sample calculation : n= - Z2 (1- α/2 ): Confidence interval 95%, α = 0.05 Z2 (1- α/2 ) = 3.8416 - p=0.314: the rate of diabetic stroke patients in the previous study - d=0.1: T he absolute error rate of research results from the sample in comparison t o t he population - n: study sample Accordingly n=83 In fact, we selected 112 patients in the study group (diabetic stroke patients) and 103 patients in the comparison group (non-diabetic stroke patients) 2.3.3 Data colle cti on me th od 2.3.3.1 Clinical data We used uniform medical records for all patients in the study - History of present illness: Ask the patient and his relatives carefully about the onset (t ime/date; circumstance: at rest , on exert ion, sleeping, waking up, psychologically stressed, taking a bath) Are there any symptoms like change in mental status, weakness, paralysis, numbness, headache, dizziness, nausea, blurred vision - Medical history: Ask about history of diabetes, hypert ension, lipid disorders, cerebral stroke, transient ischemic attack, heart diseases, atrial fibrillation, atrial fibrillation, heart failure, valvar heart diseases and ot her medical conditions - Physical examination + Neurological examination: assessment of impairment of conscious level, hemiplegia, sensory disorders, language disorders, cranial nerve paralysis, visual disturbances, dysphagia, convulsion, sphincter dysfunct ion Assessment of clinical severity in t he NIHSS scale + Medical examination: * Measurement of height, weight, waist circumference, obesity assessment based on body mass index (BMI) according to World Health Organization (2004) crit eria for Asia Pacific region Ocean * Blood pressure measurement, classifying hypert ension according to JNC VII * Det ect ing comorbidities 2.3.3.2 Paraclinical data - Biochemical blood tests were done at the department of biochemistry in T hanh Nhan Hospit al All patients were t ested for blood glucose immediately aft er admission and repeat ed fast ing plasma glucose at 6am, after no caloric intake for at least hours In the comparative group, in order to distinguish newly diagnosed with diabetes and reactive hyperglycaemia, HbA1c and twice fast ing plasma glucose t est were done - Head MRI was performed in the department of Radiology in T hanh Nhan hospit al using Magnet om C 0.35 T esla produced by Siemens + Signals: T 1W, T 2W, FLAIR, T 2*, DWI, T OF + Planes: horizontal, vertical sections 5mm t hickness for each slide (parameters of Magnet om C) + Results were interpret ed by radiologist + Dat a collection: anatomical location, size, number of new infarcts; location and number of old infarcts; location and number of lacunar infarcts + Other investigation: Complete blood count, urinalysis, electrocardiogram, carotid Doppler ultrasonography, echocardiography, chest X-ray 2.3.3.3 Diagnosis - Clinical diagnosis + Lacunar infarction + Part ial anterior circulation infarct + T otal anterior circulation infarct + Posterior circulation infarct 11 % Chart 3.5 Lacu nar syndrome s Comment: In diabetic group, clinical symptoms on admission included: hemiplegia 79.46 %, cranial nerve palsy 79.46%, hemianesthesia 41.07%, aphasia 40.18%, dysphagia (30/80 patients) 37.5%, visual impairment 31.25%, less common symptoms including disturbances of consciousness 11.61%, sphincter dysfunct ion 8.93% T he rat e of patients presenting with dysphagia and visual impairment in diabetic group was higher than t hat of comparative group (p0.05) 12 3.1.2 Metabol ic syndrome s Table 3.15 Rati o of patie nts wi th me tabol ic syndrome s Groups Metabolic syndromes Number of Yes patients Diabetic Non-diabetic group group Total 87 44 131 Percentage Number of patients 77.68 25 42.72 59 60.93 84 Percentage Total 22.32 112 57.28 103 39.07 215 No p 0.0001 Comment: The rate of patient with metabolic syndrome in diabetic group was 77.68% that was higher than data of non-diabetic group (p 0.05) 3.2 The re lati onship be twe e n diabete s and ische mic stroke 3.2.1 Characteristics of history of diabetes and some risk factors - In diabetic patients, t he rate of hypert ension was only 4.46%, the rat e of hypert ension combined with elevated LDL-C was 35.71%, the rate of hypertension combined with elevated LDL-C and 14 transient ischemic attack was 29.46%, the rat io of hypert ension accompanied by elevated LDL-C and history of stroke was 33.93%, the proportion of hypert ension coexisting with one risk fact or was 43.75% - T he rat e of patients diagnosed with diabetes for less than years and more than years were 23.21% and 76.79%, respectively Mean time was 8.3 ±3.72 (years) T he rat e of diabetics treated with injectable medicat ions was 50% - Mean plasma glucose level on admission was 11.24 ± 5.71 mmol/l in comparison to data of non-diabetic patients that was 6.06 ± 1.43 3.3.2 The re lationship betwe e n diabete s and ische mic stroke Table 3.26 The association between ti me of diabete s diagnosis and outcome Good O utcome Time of Number of patie nt Pe rce ntage Bad Number of patie nt p Pe rce ntage diagnosis Less than years ≥ years OR (95%CI) 22 84.6 15.4 50 58.1 36 41.9 0.014 3.96 (1.21-12.97) Comment: Ischemic patients who had a diagnosis of diabetes for more than years were 3.96 times are more likely to have worse outcome than those diagnosed with diabetes for less than years T his correlat ion is statistically significant (OR = 3.96, 95% CI: 1.21-12.97) 15 Table 3.28 The re lationship betwe e n plasma glucose l e vel on admission and outcome Outcome Glucose (mmol/l) Diabetic patients Good Bad Number of Percent- Number of Percentpatient age patient age