Luan an tom tat (anh) nghiên cứu đặc điểm lâm sàng, cận lâm sàng của nhồi máu não ở người cao tuổi có bệnh đái tháo đường

Diabetes increases the risk of atherosclerosis by 2-3 times and doubles the risk of stroke compared with normal people.. Patients with diabetes also experience co-occurring risk factors

108 INSTITUTE O F C LINICAL MEDICAL AND

PHARMACEUTICAL SC IENC ES

NGUYEN THE ANH

STUDY O N C LINICAL AND PARAC LINICAL O F ISC HEMIC S TRO KE IN THE ELDERLY PATIENT W ITH

108 INSTITUTE O F C LINICAL MEDICAL AND

PHARMACEUTICAL SC IENC ES

Sci entific Supervisors:

1 Prof P hD Le Quang Cuong

2 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:

1 Nat ional Library of Viet nam

2 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 5 million die and ot her 5 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 2 diabet es, 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 at heroma, hyperlipidaemia, hypert ension, which t ogether cause early, severe ischemic stroke and slower recovery In Viet nam, there hasn’t been any study on ischemic stroke that specified in elderly with diabetes

Hence our research: “Stu dy on clinical and paracl inical

ch aracteristics of ischemic stroke in th e elde rl y wi th di abe te s”

T here are two object ive:

1 Research on neurological characteristics, m etabolic syndrom es and m agnetic resonance imaging of ischem ic stroke in the elderly with diabetes

2 Consider the association between diabetes and cerebral infarction in the elderly

NEW MAIN C O NTRIBUTIO N O F THE THESIS

- T his is a prospect ive, descriptive, controlled study which systemat ized clinical, biochemical and imaging charact erist ic of ischemic stroke in elderly with diabetes T he results are described in detail, and are compared with pat ients 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, 1 diagram, 9 images, 172 references including 43s in Viet namese, 129s in English and 2 related art icles

*Acronyms: IS-ischemic stroke

C HAPTER 1: LITERATURE REVIEW

1.1 Abou t isch e mic s troke

1.1.1 De fi niti on and cl assifi cati on of isch e mic s troke

T he occurrence of IS is the consequence of a sudden decline in cerebral circulat ion due t o part ial or total cerebral art ery occlusion

Clinical manifest at ions of IS are sudden appearances of focal neurologic signs

1.1.2 C ause s of isch e mic s troke

According to T OAST ischemic stroke causes can be cat egorized int o five major group: major vascular disorders, cardiac disorders, small vessel disorders, other causes and unknown causes

1.1.3 C linical m anife stati ons

Sudden onset of focal neurologic sign depends on t he size and locat ion 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 di agnosis tools

- MRI is a met hod with high sensitivit y, surpass computerized tomography in t he diagnosis of IS

- Ot her tests also play roles in the diagnosis of IS, such as Doppler ultrasound of ext ernal carotid artery, elect rocardiography, biochemistry t est et c

2.1 Ische mic s troke in e lde rl y wi th diabe te s

2.1.1 Abou t diabe te s

- Diabetes is a chronic metabolic disorder, with genetic fact ors

T he disease is charact erized by increased blood glucose T he main cause is absolute or relat ive 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 1 diabetes, type 2 diabetes and

gestat ional diabet es 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 2 diabet es Insulin resistance is a central factor in metabolic syndrome Met abolic syndrome has six major components: abdominal obesity, at herogenic dyslipidaemia, hypert ension, insulin resistance, proinflammatorystat es ,

- Vascular complicat ion in pat ient with diabetes Cardiovascular diseases, especially at herosclerosis, are major causes of disability and deat h in people with diabet es It significantly increases the risk

of progressive coronary artery disease, cerebrovascular disease and other peripheral arterial diseases

2.1.2 Nati onal and i nte rn ati 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, at rial fibrillat ion, 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 diabet ic group

- T he rat e of first-trimester disability (on t he Rankin and Bart hel scale) of stroke pat ient was higher in diabetic group than that of non-diabetic group

- HbA1c were not associat ed with outcomes of ischemic stroke

C HAPTER 2: SUBJEC TS 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

Pat ients 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 pat ients

- Controlled group: Non-diabetic stroke pat ients

2.2.1 Eligibility cri te ri a

- Pat ients 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 1 imaging, high signal int ensity seen at

T 2 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 pat ient 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 t olerance t est (OGT T )

+ HbA1c ≥ 6.5%

2.2.2 Excl usion cri te ri a

- Pat ients with haemorrhage-ischemic stroke

- Pat ients with IS accompanied by cerebrovascular malformat ion

or brain tumours

- Pat ients were t reated with t hrombolytic therapy

- Pat ients with a history of stroke with sequelae of grade 1 or higher on a modified Rankin scale

- Pat ients with a history of mental disorders and / or traumatic brain

- p=0.314: the rate of diabetic stroke pat ients in the previous study

- d=0.1: T he absolute error rate of research results from the sample in comparison t o t he populat ion

- n: study sample

Accordingly n=83 In fact, we selected 112 patients in the st udy group (diabetic stroke pat ients) and 103 pat ients in the comparison group (non-diabetic stroke pat ients)

2.3.3 Data colle cti on m e th od

2.3.3.1 Clinical data

We used uniform medical records for all pat ients in the st udy

- History of present illness: Ask the pat ient and his relatives carefully about the onset (t ime/dat e; circumstance: at rest , on exert ion, sleeping, waking up, psychologically stressed, taking a bath) Are there any symptoms like change in mental stat us, weakness, paralysis, numbness, headache, dizziness, nausea, blurred vision

- Medical history: Ask about history of diabetes, hypert ension, lipid disorders, cerebral stroke, transient ischemic at tack, heart diseases, at rial fibrillat ion, at rial fibrillat ion, 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 pat ients 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 8 hours In the comparative group, in order to distinguish newly diagnosed with diabetes and react ive 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 collect ion: anat omical locat ion, size, number of new infarct s; locat ion and number of old infarcts; locat ion and number of lacunar infarct s

+ Ot her investigat ion: Complete blood count, urinalysis, cardiogram, carotid Doppler ultrasonography, echocardiography, chest X-ray

electro-2.3.3.3 Diagnosis

- Clinical diagnosis

+ Lacunar infarction

+ Part ial anterior circulat ion infarct

+ T otal anterior circulat ion infarct

+ Posterior circulat ion infarct

- Diagnosis of comorbidities and combined syndromes

- Met abolic syndrome: NCEP: AT P III 2005 Diagnostic Crit eria for Met abolic Syndrome Presence of three or more of these components:

+ Abdominal obesity: Increased waist circumference: male ≥ 90

cm, female ≥ 80cm

+ Elevat ed T riglycerides ≥ 150 mg/dL (1.70 mmol/L) + HDL-cholesterol < 40 mg/dL (< 1.04 mmol/l) for male, or <

50 mg/dL (< 1.3 mmol/l) for female

+ Systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 85 mm Hg of medical history of hypertension treated with antihypert ensives

+ Fasting plasma glucose ≥ 5.6 mmol/L

- Comorbidities: heart diseases, pneumonia, renal failure et c

2.3.3.4 Assessm ent of outcom e after treatm ent based on m odified

Rankin scale :

- Good: Rankin 0, 1, 2, 3;

- Bad: Rankin 4, 5, 6

2.4 Analysis and proce ssing of data

- Using the medical stat istical method T he data was checked, filt ered before import ing and analysed by SPSS 22.0 software

- Using chi-squared test, fisher's exact test, t-test Whitney test; ANOVA/Kruskal Wallist test OR, 95% confidence int ervals, and stat istically significant at p <0.05

Student/Mann-C HAPTER 3 RESEARStudent/Mann-C H RESULTS

3.1 C linically neurological ch aracteristics, metabolic syndrome and MRI findings of ischemic stroke in e lderly patients wi th di abe te s 3.1.1 C linically n e urological ch aracte ri sti cs

- Ge neral fe atu re s: 215 pat ients with ischemic stroke, aged ≥ 60

years old

+ Research group (ischemic stroke pat ients with diabet es): mean age was 71.30±6.68; rat e of female/male was1.43; the number of pat ients aged from 60-74, 75-84 and over 85 accounted for 69.64%; 25.89%, 4.46%, respectively

+ Comparative group (ischemic stroke patients without diabet es): mean age was 71.72±7.80; rat e of female/male was 1.01; the number

of pat ients aged from 60-74, 75-84 and over 85 accounted for 64.8

C hart 3.5 Lacu nar s yndrome 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 (p<0.05)

Comment: In diabetic group the rat e of pure motor hemiparesis was 41.42%, sensorimotor stroke 18.57%, pure sensory stroke 14.28%,

At axic hemiparesis 8.57%, Dysart hria-clumsy hand syndrome 7.14% T here was no differences in rat e of lacunar syndromes in two groups (p>0.05)

%

of patient

age

infarction were 13.43% and 8%, respect ively There was a difference

in distribution of infarct s in head MRI bet ween diabet ic pat ients and non-diabetic pat ients (p<0.05)

Table 3.20 Locati on of lacu nar i nfarcts

Pe rce age

nt-Numbe r

of patie nts

Pe age

rcent-Basal nuclei, internal

capsule

0.05 Corona radiate,

centrum ovale accounting for 22.85%, and of t halamus (22.85%)

T here was no difference in locat ion of lacunar infarcts in two groups (p > 0.05)

3.2 The re lati onship be twe e n di abe te s and i sch e mic stroke

3.2.1 Characteristics of history of diabetes and some risk factors

- In diabetic pat ients, t he rat e of hypert ension was only 4.46%, the rat e of hypert ension combined with elevat ed LDL-C was 35.71%, the rate of hypertension combined with elevat ed LDL-C and