RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
DISSERTATION
1.NAME OF THE CANDIDATEAND ADDRESS
( in block letters ) / DR. DHEERAJ KUMAR SINGHANIA
BMC MEN’S PG HOSTEL
1ST MAIN, CHAMRAJAPET
BANGALORE-560018
2.NAME OF THE INSTITUTION / BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE, BANGALORE
3.COURSE OF STUDY AND SUBJECT / M.D. GENERAL MEDICINE
4.DATE OF ADMISSION TO THE COURSE / MAY 2nd , 2009
5.TITLE OF THE TOPIC / A STUDY OF ASSOCIATION OF SERUM HOMOCYSTEINE LEVEL IN PATIENTS OF STROKE IN YOUNG
6. BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR STUDY
Stroke remains a major cause of mortality and morbidity worldwide.1 The burden of stroke arises largely from the elderly population. However, there remains a small but significant subset of younger patients with ischemic stroke, in whom conventional vascular risk factors play a smaller role. Unusual causes of stroke, such as arterial dissection or thrombophilia, are more common, although the final cause may remain undetermined in 21% to 31%.2
There is growing evidence that high homocysteine levels contribute to the pathogenesis of ischemic stroke. Homocysteine is believed to cause atherogenesis and thrombogenesis via endothelial damage, vascular smooth muscle proliferation, and coagulation abnormalities. High homocysteine levels are associated with increased risk of cardiovascular and cerebrovascular disease, although there are studies that show no increase in risk, and there is still debate as to the strength and validity of the association. This disparity may be partly explained by methodological differences between the
different studies, such as use of fasting and non fasting samples, differing timing of sampling post-stroke and different subtypes of strokes studied.3
There is a lot of research in the field of stroke in young and its various etiologies. Various studies are currently assessing the role of homocysteine as a independent risk factor in stroke in young patients and its possible implication in prevention. This study will correlate the serum homocysteine level in patients of stroke in young.
6.2 REVIEW OF LITERATURE
A study done by Tan NC et al concluded that hyperhomocysteinemia is an independent risk factor for ischemic strokes in young Asian adults. The relationship between increasing homocysteine and stroke risk is strong, graded, and significant. The association with large-artery strokes suggests that hyperhomocysteinemia may increase stroke risk via a proatherogenic effect.1
A study done by Kittner SJ et al concluded that there is an independent association between elevated homocysteine level and stroke in young women.2
A study done by Eikelboom JW et al concluded that there is a strong, graded association between increasing plasma homocysteine and ischemic stroke caused
by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke.3
A study done by Kristensen B et al concluded that a moderately elevated increase in homocysteine levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting homocysteine levels did not differ between patients and controls. A moderately elevated increase in homocysteine after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease.4
A study done by Usman Khan et al on UK black stroke population concluded that homocysteine levels were elevated and highest levels were found in lacunar stroke with leukoaraiosis.5
A study done by Zolianthanga Zongte et al in 93 cerebrovascular accident cases admitted in the hospital concluded that hyperhomocysteinemia is associated with cerebrovascular accident with male preponderance, which increases with advancing age.6
A study done by Coull BM et al concluded that a moderately elevated plasma homocysteine concentration may be an independent risk factor for cerebrovascular disease.7
A study conducted by Hassan A et al concluded that hyperhomocysteinaemia is an independent risk factor for SVD, particularly ischaemic leukoaraiosis, and this effect may be mediated via endothelial dysfunction.8
6.3 OBJECTIVES OF THE STUDY:
To determine the association of serum homocysteine level in patients of stroke in
young.
7. MATERIALS AND METHODS
7.1 SOURCE OF DATA:
The study will be conducted in patients admitted to Victoria Hospital and Bowring & Lady Curzon Hospital attached to Bangalore Medical College and research institute, Bangalore.
7.2 METHOD OF COLLECTION OF DATA
1. INCLUSION CRITERIA:
a) Patients 15-45 years of age will be included.
b) Only first ever ischemic stroke cases proven by CT scan/ MRI brain will be
included.
2. EXCLUSION CRITERIA:
a) Hypertension
b) Diabetes mellitus
c) Transient ischemic attack
d) Hyperlipidemia
e) Smokers
f) Case of valvular heart disease
g) Cases of HIV and Neurosyphilis
h) Connective tissue disorders
3. SAMPLE SIZE AND DESIGN: A case control study with a minimum of 30 cases of ischemic stroke of age 15-45 years and equal number of age and sex matched controls will be studied according to protocol.
Controls will be volunteers taken from apparently healthy population preferably from patient’s attenders. Informed consent will be taken from controls.
4. DURATION OF STUDY: Over a period of two years from October 2009 to
November 2011.
Statistical methods.
Statistical analysis is performed using Chi square test/odds ratio.
7.3 DOES THE STUDY REQUIRES ANY INVESTIGATIONS OR
INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER
HUMANS OR ANIMALS? IF SO DESCRIBE BRIEFLY
STUDY ON ANIMAL INTERVENTION IS NOT REQUIRED.
INVESTIGATIONS REQUIRED
· Complete haemogram with ESR
· RBS
· Blood VDRL & CSF VDRL if required
· ELISA for HIV
· Blood urea & S.creatinine
· Fasting lipid profile
· Total serum homocysteine level
· Urine routine
· CT Scan Brain/ MRI Brain
· ECHO
· ANA / RA factor and any specific investigation if indicated
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3
YES
8. LIST OF REFERENCES
8.1 JOURNAL REFERENCES
1. Tan NC, Venketasubramanian N, Saw SM, Tjia HT. Hyperhomocysteinemia and risk of ischemic stroke among young Asian adults. Stroke. 2002;33:1956–1962.
2. Kittner SJ, Giles WH, Macko RF, Hebel JR, Wozniak MA, Wityk RJ et al. Homocysteine and risk of cerebral infarction in a biracial population, the stroke prevention in young women study. Stroke. 1999;30:1554–1560.
3. Eikelboom JW, Hankey GJ, Anand SS, Lofthouse E, Staples N, Baker RI. Association between high homocysteine and ischemic stroke due to large and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke. 2000;31:1069–1075.
4. Kristensen B, Malm J, Nilsson TK, Hultdin J, Carlberg B, Dahlen G et al. Hyperhomocystenemia and hypofibrinolysis in young adults with ischemic stroke. Stroke. 1999;30:974–980.
5. Usman Khan, Carollyn Crossley, Lalit Kalra, Anthony Rudd, Charles DA Wolfe, Paul Collinson et al. Homocysteine and its relationship to stroke subtypes in a UK black population ,the South London ethnicity and stroke study. Stroke. 2008;39:2943-2949.
6. Zolianthanga Zongte, L Shaini, Asis Debbarma, Th Bhimo Singh, S Bilasini Devi and WG Singh. Serum homocysteine level in cerebrovascular accidents. Indian Journal of Clinical Biochemistry. 2008; 23(2):154-157.
7. Coull BM, Malinow MR, Beamer N, Sexton G, Nordt F, de Garmo P. Elevated plasma homocysteine concentration as a possible independent risk factor for stroke. Stroke. 1990;21:572–576.
8. Hassan A, Hunt BJ, O’Sullivan M, Bell R, D’Souza R, Jeffery S et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain. 2004;127: 212–219.
8.2 TEXT BOOK REFERENCES:
1. PM Dalal. Ischemic cerebrovascular diseases. Siddharth N Shah,M Paul Anand, Aspi R Billimoria, Sandhya A Kamath, Dilip R Karnad, YP Munjal, Milind Y Nadkar, PS Shankar, ME Yeolekar. API textbook of medicine volume 2, 8th Edition. The Association of Physicians of India 2008;19:1163.
2. Allan H Ropper, Robert H Brown. Cerebrovascular diseases. Adam’s and Victor’s principles of neurology, 8th Edition. McGraw Hill 2005;34: 708-711.
3. Jose Biller, Besty B Love, Michael J.Schneck. Vascular diseases of the nervous system, ischemic cerebrovascular disease. Walter G Bradley, Robert B Daroff, Gerald M Fenichel, Joseph Jonkovic. Neurology in clinical practice volume 2, 5th Edition. Elesvier 2008;55A:1191-1192.
9. SIGNATURE OF THE CANDIDATE
(DR. DHEERAJ KUMAR SINGHANIA)
10. REMARKS OF THE GUIDE: In young adults with ischemic stroke elevated fasting homocysteine level is an important risk factor. The study has been taken to determine association of serum homocysteine level in young stroke patients.
11. NAME AND DESIGNATION OF
(In block letters)
11.1 GUIDE : DR. C.M. SHAMAIAH
PROFESSOR, DEPT OF MEDICINE
BANGALORE MEDICAL COLLEGE &
RESEARCH INSTITUTE ,
BANGALORE
11.2 SIGNATURE :
11.3 CO GUIDE (IF ANY) : DR. RITA CHRISTOPHER
PROFESSOR AND HEAD
DEPT OF NEUROCHEMISTRY
NIMHANS, BANGALORE
11.4 SIGNATURE :
11.5 HEAD OF THE DEPARTMENT: DR.VASANTHA KAMATH MD, FICP
PROFESSOR AND HEAD
DEPARTMENT OF MEDICINE
BANGALORE MEDICAL COLLEGE
& RESEARCH INSTITUTE ,
BANGALORE
11.6 SIGNATURE :
12.
12.1 REMARKS OF THE DIRECTOR AND DEAN
12.2 SIGNATURE :
1