Interesting cases of young stroke

Prof.S.RAMASAMY’s unit

Dr.A.Prakash

Case 1

35 year old male Mr. Arul, businessmanc/o inability to use right UL & LL since previous day nightc/o inability to talk since previous day night.h/o right facial lag with deviation of the mouth to the left

side.No h/s/o sensory disturbances.No h/s/o autonomic disturbances. No h/s/o cerebellar symptoms.No h/s/o cortical sensory disturbances.No h/s/o meningitis.No h/o wasting/twitching.

A known alcoholic for past 2 years; weekly twice

Not a smoker.

Not a k/c of DM/HTN/CAD/BA/CVA/seizure.

No h/o chronic drug intake.

No relevant family history.

General examination

Conscious, aphasic, not dyspnoeic, afebrile, response to oral commands,

No pallor/cyanosis/clubbing/jaundice/PE/GLA JVP not elevated Hydration adequate no neurocutaneous markers Vitals: BP-110/80mmHg, PR-88/min, felt in all

peripheral vessels, left carotid pulse feeble, RR-16/min, Temp N

Examination of CNS

HFs- aphasic Cranial nerves- right sided UMN facial palsy Motor system- f/o right sided hemiplegia Sensory system normal No Cerebellar signs No signs of meningeal irritation Spine & cranium normal

Examination of other system

CVS- S1, S2 +, no murmur, left carotid bruit +

RS- NVBS +, no added sounds. Abdomen –soft, no organomegaly.

Provisional diagnosis

CVA/ RIGHT HEMIPLEGIA/ RIGHT UMN FACIAL PALSY/ YOUNG STROKE-?CAUSE.

CASE 2

Krishnamoorthy 34 year old male, shopkeeper,c/o inability to use left UL & LL since previous nightc/o facial lag on the left side with deviation of angle of

mouth to right sideNo h/o loss/difficulty in speech..No h/s/o sensory disturbances.No h/s/o autonomic disturbances. No h/s/o cerebellar symptoms.No h/s/o cortical sensory disturbances.No h/s/o meningitis.No h/o wasting/twitching.

Not an alcoholic/smoker.

Not a k/c of HTN/DM/CVA/IHD/BA/PT/seizure.

No h/o chronic drug intake.

No relevant family history.

General examination

Conscious, drowsy, not dyspnoeic, afebrile, response to oral commands,

No pallor/cyanosis/clubbing/jaundice/PE/GLA JVP not elevated. Hydration adequate., no neurocutaneous markers. Vitals: BP-120/80mmHg, PR-80/min,

RR-16/min, Temp N

Examination of CNS

HFs- NORMAL Cranial nerves- LEFT sided UMN facial palsy Motor system- f/o left sided hemiparesis. Sensory system normal. No Cerebellar signs. No signs of meningeal irritation. Spine & cranium normal.

Examination of other systems

CVS- S1, S2 +, no murmur, RS- NVBS +, no added sounds. Abdomen –soft, no organomegaly.

Provisional diagnosis

CVA/LEFT SIDED HEMIPARESIS/LEFT UMN FACIAL PALSY/ YOUNG STROKE-?CAUSE.

INVESTIGATIONSINVESTIGATIONS CASE 1 CASE 2

HB 11.8 12.2

TC 7600 6800

DC P66, L33, E1 P71, L26, E2

PLATELET 1.4 LAKS 1.6 LAKS

PCV 35% 37%

RBC 3.9 MILLION 3.6 MILLION

ESR 8/22 10/26

PERIPHERAL SMEAR NORMAL NORMAL

INVESTIGATIONS CASE 1 CASE 2

BLOOD SUGAR 113 MG% 97

UREA 22 25

SR CREATININE 0.8 0.8

Na 134 137

K 3.8 3.8

Cl 106 102

HCO3 23 23

urinalysis SUG NIL, ALB NIL, 1-2 PC SUG NIL, ALB NIL, 2-4 PC

PT/APTT 17 (C 12-15), 25 (C 26-39) 16 , 25

LIPID PROFILE CASE 1 CASE 2

TOTAL CHOLESTEROL 173 mg% 185

TRIGLYCERIDES 129 136

HDL 39 42

LDL 99 88

VLDL 35 30

investigations Case 1 Case 2

HIV NR NR

RHEUM ATOLOGICAL PROFILE

ANA NEG NEG

RAF NEG NEG

ACLA IgG IgM IgA

APLA IgM IgG

2.88 GPL/ml (N <10)3.04 MPL/ml(N <7)3.2 APL/ml (N <15)

NOT DETECTABLE ( N <15)3 U/ml (N <15)

5.64.83.3

NOT DETECTABLE3.4 u/ml

LA NEG NEG

INVESTIGATIONS CASE 1 CASE 2

BLEEDING TIME 3 MIN 4 MIN

PROTEIN C 142.1 (n 70-140) 90

PROTEIN S 138.4 (N 60-150) 110

ANTI THROMBIN III 24 (n 22-39MG/DL) 26

HOMOCYSTEINE 126.8 (n 5-16) 150.4

INVESTIGATIONS CASE 1 CASE 2

CAROTID DOPPLER PLAQUE IN LEFT CAROTID BULB

NORMAL

ECHO NORMAL NORMAL

CT BRAIN NORMAL RIGHT SIDED INFARCT

MRI BRAIN LEFT MCA INFARCT

CXR NAD NAD

OPINION CASE 1 CASE 2

CARDIOLOGY ECHO- NCARDIAC STATUCS NORMAL

ECHO –NCARDIAC STATUS NORMAL

NEUROLOGY CVA/RIGHT HEMIPLEGIA/ RIGHT UMN FACIAL PALSY/YOUING STROKE DUE TOHYPERHOMOCYSTENEHYPERHOMOCYSTENEMIAMIA

CVA/LEFT HEMIPARESIS/ LEFT UMN FACIAL PALSY/YOUNG STROKE DUE OT HYPERHOMOCYSTENEHYPERHOMOCYSTENEMIAMIA

OPHTHALMOLOGY LENS- N, FUNDUS- N, LENS- N, FUNDUS-N

DIAGNOSIS

YOUNG STROKE DUE TO HYPERHOMOCYSTINEMIA.

Young stroke

A stroke or CVA is defined by this abrupt onset of a neurologic deficit, that is attributable to a focal vascular cause as occurred if neurological signs & symptoms last for >24 hrs.

Young stroke means stroke occurring in persons < 40 years of age.

Causes of young stroke

Premature atherosclerosis Cardiovascular causes RHD Infective endocarditis Embolism Prosthestic valve MVPS Left atrial myxoma Specific arteritis – TB, sypilis Nonspecific arteritis- aortoarteritis, moya moya ds, takayasu, trauma,

drugs Collagen vascular diseases- SLE, APLAS, spontaneous dissection of

carotid Inborn errors of metabolism- homocystinuria, fabrys angiokeratosis hematological causes- sickle cell ds, ITP,

THROMBOPILIA

CONGENITAL- Activated protein c resistant syndrome (factor V leiden mutation) Protein C & S deficiency Antithrombin III def Hyperhomocystinemia (MTHFR mutation) TPA def Hyperfibrinogenemia Factor XII def Increased conc of factor VIII Heparin cofactor II def Prothrombin gene mutation

Acquired

Increased age Cancer Pregnancy OCP &HRT APLAS Nephrotic syndrome Myeloproliferative disorder PNH Hyperhomocystinemia Increased factor VIII Heparin induced trombocytopenia Increased viscosity

Approach to iscemic stroke

Emergent (for Rx purpose) History & physical examination CT brain ECG CBC PT & aPTT Blood sugar Serum electrolytes RFT urinalysis

Non-emergent ( to r/o causes) LAB INVESTIGATIONS Serum lipid profile ESR HIV serology Rheumatological profile –ANA, RA, ACLA, LA SPECIAL HEMATOLOGICAL STUDIES HB electrophoresis BT & Thrombin time Protein C & S Antithrombin III Serum fibrinogen

Imaging study Carotid doppler MRI brain ECHO Cerebral angiograpy

Approac to a Hemorragic stroke

Emergent (for Rx purpose) History & physical examination CT brain ECG CBC PT & aPTT Blood sugar Serum electrolytes RFT urinalysis

Non emergent LAB INVESTIGATIONS Serum lipid profile ESR HIV serology Hematology Peripheral smear HB electrophoresis Imaging CT brain Echo MRI brain Cerebral angiograpy

Non emergent LAB INVESTIGATIONS Serum lipid profile ESR IV serology Hematology Peripheral smear HB electrophoresis Imaging CT brain Eco MRI brain Cerebral angiograpy

Homocystinuria

Homocysteine is an intermediate product in the metabolism of amino acid metheonine

Homocystinemia can be caused by an error in metabolism of sulfur containing amino acid

Causes of elevated homocysteine level--- A genetic defect in MTHFR gene nutritional def of folate ,vit. B12, vit. B6

Homocystinuria classified in to 4 types Classic homocystinuria due to reduced activity of cystathionine

beta synthase (the pyridoxol phosphate dependent enzyme that condenses homocystein with serine to form cystathionine

Clinical features Dislocated optic lenses, MR, marfanoid habitus, osteoporosis,

life threatening thrombotic vascular diseases Classic homocystinuria can be diagnosed with analysis of

plasma amino acids showing elevated metheonine, and presence of free homocystein. Total plasma homocystein is also extremely elevated usually >100 micromol

Treatment

Special diet restricted in protein & metheonine & supplemented with cystein

Oral pyridoxine (25-500 mg/d) Folate def should be prevented by adequate

supplementation Betaine is also effective in reducing

homocysteine level in pyridoxine unresponsive patient

Other form of homocysteinuria

Due to result of impaired remethylation of homocystein to metheonine---

Metheonine synthase def- MR, hypotonia, seizures, megaloblastic anemia

Two essential cofactor def (5-methyl THF & methyl cobalamine)

Changes of homocystein levels are also observed with increased age, smoking, post menopausal women, renal failure, hypothyroidism, leukemias, IBD, psoriasis, during therapy with drugs such as methotrexate, N2O, isoniazid and some anti epileptic agent

pathophysiology

homocystein acts as an atherogenic & thrombophilic agent

An increased in plasma homocystein represents is an independent risk factor for coronary, cerebro vascular & peripheral arterial disease as well for DVT

homocystein is synergistic with hypertension & smoking and it is additive with other risk factor that predispose to arterial disease

In defective MTHFR gene causes premature Atherosclerosis as well as stroke in affected individuals

Cell culture studies suggest that homocystein may have prothrombotic on endothelium & vascular smooth muscle

Mild hyperomocystinemia is an independent risk factor for increased carotid artery wall thickeness & plaque formation

It also increases endothelial cell injury, platelet aggregation, and abnormalities of the clotting cascade by activations of factor V, X, XII

Studies supportive for elevated homocystein is an independent risk factor for young stroke.

Framingham study: the relative risk for stroke associated with non-fasting levels of 14.24 to 219.84 micromol/L compared with level of 4.13 to 9.25 micromol/L was 1.82 (95% confidence interval ).

Rotterdom study:Rotterdom study: relationship between elevated homocystein levels in the elderly as well as young, the risk of stroke and myocardial infarction are found a risk of increase of 6 -7% for every 1 micromol/L increse in total plasma homocystein..

In another case control studyanother case control study of 80 patients with stroke between the age of 18 to 44 years, a 4.8 fold of increase of iscemic stroke was found in those with post-metheonine load elevations in palsma homocystein levels.

Hyperhomocysteine level is an Hyperhomocysteine level is an independent risk factor for young strokeindependent risk factor for young stroke.

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