الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Stroke is the second commonest cause of death and the principal cause of adult disability in the world and two thirds of all stroke deaths occur in low-income and middle income countries. About one in ten of all deaths in these communities are attributable to cerebrovascular diseases and stroke is now a major health problem for many countries. In these countries, the burden of stroke was 5-14 disability-adjusted life years lost per 1000 population.
Cerebrovascular stroke is a complex genetic disorder with variable phenotypes. Family history is recently being focused on by studying family pedigree, with much attention to the genetic base of stroke and the role of inflammatory mediators and immunological reaction in relation to cerebrovascular stroke regarding pathogenesis, prognosis and outcome.
A growing body of evidence primarily from animal models with cerebral ischemia and preliminary human studies, using linkage analysis, association studies and others has implicated genetic influences in the pathogenesis of multifactorial ischemic stroke. However the identification of individual causative mutations remains problematic.
This study attempts to investigate the role of genetic factors represented by ACE gene insertion-deletion poly-morphism in small versus large vessels diseases. Also the role of different risk factors of ischemic cerebrovascular disease, in small versus large vessels disease was investigated.
This study was carried out on two equal groups of adult patients with ischemic stroke and 30 apparent healthy adults as a control group. Both patients and controls were aged above 40 years, and they were closely matched as regards age and sex factors.
The patients groups were:
30 patients with cerebral small vessels disease (Group Ia)
30 patients with cerebral large vessels disease (Group Ib)
All patients were subjected to the following:-
1. Clinical evaluation including history taking and complete physical, medical and neurological examination using a modified form of the cerebrovascular stroke sheet of the Neurology department, Ain Shams University.
2. Family pedigree study
3. Assessment of the severity of the stroke using the National Institute of Health Stroke Scale (NIHSS) and activity of daily living using modified Barthel Index (BI).
4. Laboratory investigations including:
a) Routine laboratory investigations: complete blood count (CBC) and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fasting and 2 hours post-prandial blood sugar levels, lipid profile, serum uric acid, liver and kidney functions tests and serum electrolytes.
b) Genetic profile: polymerase chain reaction (PCR) was performed in the Molecular Genetics Laboratory, Department of Genetics, Faculty of Agriculture, Ain Shams University to detect the presence of genetic polymorphism and genotyping of the ACE gene.
5. ECG and trans-thoracic echocardiography
6. Carotid duplex
7. Neuroimaging: imaging was performed initially by CT scan to exclude intracranial hemorrhage and to diagnose cerebral infarction, and then MRI imaging according to the stroke protocol of Ain Shams University Specialized Hospital will be done.
Results
Clinical results
The age of the patients in the cerebral small vessel patient group (group Ia) ranged from 43-75 years with a mean age of 61.1± 8.66 years, while the age of patients in the cerebral large vessel patient group (group Ib) ranged from 42-84 years with a mean age of 66.87± 9.3. On the other hand the age of the controls ranged from 42-81 years with a mean age of 62.23± 8.96 years.
The family history of either stroke or one of the clinical risk factors was positive in 20 patients (66.7%) in group Ia. Among those, positive family history of stroke was present only in 9 patients (30%). On the other hand, the family history of either stroke or one of the clinical risk factors was positive in 17 patients (56.7%) in group Ib. Among those, positive family history of stroke was present only in 11 patients (36.7%).
Hypertension was found in 27 patients (90%) in group Ia, but 24 patients (80%) in group Ib were hypertensive. In group Ia, 21 patients (70%) were found to be diabetic while in group Ib, only 11 patients (36.7%) were found to be diabetic. Ischemic heart disease was found in 10 patients (33.3%) in group Ia, but 5 patients (16.7%) in group Ib had history of ischemic heart disease.
As regards smoking, 9 patients (30%) in group Ia were smokers while in group Ib, 12 patients (40%) were smokers. Transient ischemic attacks were reported to be positive in 4 patients (13.3%) in both patients groups.
There was no statistical significant difference between patients with small and large vessels diseases as regards the distribution of clinical risk factors except for diabetes mellitus which was significantly more associated with small vessels disease patients group.
Laboratory results
On comparing the values of the laboratory risk factors between both patients groups, there was a statistical significant difference between group Ia and group Ib as regards the mean levels of FBS and 2hours PPBS. Otherwise, no significant differences were found between patients with small and large vessels disease as regards the mean level of other parameters.
As regard CRP, it was positive in 16 patients (53.3%) in small vessels disease patients group while 22 patients (73.3%) in large vessels disease patients group were CRP positive. There was no significant difference between patients with small and large vessels disease as regards the distribution of CRP.
Outcome results
On comparing between groups with small and large vessels disease according to the level of NIHSS and modified BI scores, there was a statistical significant difference between both patients groups. Patients with small vessels disease showed statistically significant lower NIHSS score and higher modified BI score when compared to patients with large vessels disease.
Genotyping results
The DD genotype was more common in cases compared with control subjects (53% versus 10%). On the other hand, there was no statistical significant difference between patients with small and large vessels diseases as regards the distribution of ACE genotypes.
Patients with high triglycerides serum levels (>200 mg/dl) had a significantly higher rate of deletion than those with low triglycerides serum levels (<200 mg/dl). Other risk factors show no specific significant genotype.
On comparing different ACE genotypes according to both NIHSS and modified Barthel index scores, there were no statistical significant differences between the levels of NIHSS and modified BI scores in different ACE genotypes.
To conclude that different stroke risk factors contribute to the functional outcome of stroke patients; and that genetic factors play an important role in the pathogenesis of stroke. Further genetic research is needed to determine the risk factors profile of each subtype of ischemic stroke. The ultimate goal of genetic research will be, not only to provide new insights into factors influencing the outcome of stroke, but also to identify people at greater risk of ischemic stroke and new therapeutic targets when preventive strategies have failed.