1. stroke

2. Stroke is defined as: rapidly developing clinical signs of focal cerebral dysfunction, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin.

3. Epidemiology (in points)
>500,000 strokes /year
Third cause of death
25-30% occur <65 y/o
Leading cause of disability
15% die shortly after stroke
10% requiring care in a nursing home
40% have moderate –severe impairment require special care
25% recover with minor impairment
10% of stroke recover almost completely

4. Classification:
Stroke is classified by the pathology as either an infarction or a hemorrhage
Ischemic infarction:Two major mechanisms are responsible
for ischemia in acute stroke: thromboembolism and hemodynamic failure.
classified into various subgroups(based on the mechanism of the ischemia and the type and localization of the vascular lesion).
 (1) Large-vessel Atherosclerotic Infarction:
Atherosclerotic plaque usually locate at a bifurcation or curve in one of the larger vessels(most common sites:bifurcation of the common carotid artery origins of MCA and ACA, and the origins of the vertebral from the subclavian arteries.)

5. 2) Cardiac Embolism
accounts for 20% to 30% of all ischemic stroke
Embolism originates from a cardiac source of thrombus, as a small particle of thrombus breaks off from the source and is carried through the bloodstream until it lodges in an artery too small to allow it to pass( other types of particles that may embolize include: neoplasm, fat, air, or other foreign substances)
(3) Small vessel (lacunar)
20% to 30% of all ischemic strokes.
Mechanism of small vessel disease described as a tiny focus of microatheroma or lipohyalinosis stenosing one of the deep penetrating arteries.
Secondary to long-standing hypertension or diabetes mellitus.
(4) Cryptogenic Infarction
When the cause of infarction is undetermined (in spite of extensive work up)

6. According to type and localization of the vascular lesion
Anterior circulation =ICA, ACA, MCA
Posterior circulation=vertibrobasilar
Risk factors (increase the liability to stroke)
Modifiable:
Hypertension
Cardiac disease
Atrial fibrillation
Endocarditis
Mitral stenosis
Recent large MI
cigarette smoking
Sickle cell sisease
TIA
Asymptomatic carotid stenosis
Physical inactivity
Use of birth control pills Infective

7. Potentially Modifiable
Diabetes mellitus,
Hyperhomocyteinemia
Left ventricular hypertrophy
Non-modifiable
Age
Gender
Hereditary/familial factors
Race/ethnicity
Prior medical history
Geographic location

10. interruption of blood flow through vascular occlusion.
A decrease in regional CBF leads to diminished tissue perfusion.
The difference in tissue outcome following arterial occlusion is based on the concept that CBF thresholds exist, below which neuronal integrity and function are differentially affected

11. Over a range of mean blood pressures of 50 to 150 mmhg, the small vessels are able to dilate and constrict in order to maintain cerebral blood flow in a narrow range..(cerebral autoregulation)
this accommodation fails at the extreme of blood pressure CBF will follow systemic pressure passively..
In persistent large vessel occlusion,local perfusion pressure, which is the main factor influencing the eventual outcome of tissue depends on several factors such as the presence and extent of collaterals and systemic arterial pressure (due to loss of the ischemic brain’s autoregulatory capacity).
cerebral ischemia may be triggered by conditions that decrease perfusion proximally to the arterial lesion (systemic hypotension or low cardiac output) and increase metabolic demands(fever, acidosis)

12. Strokes occurring through these mechanisms are located predominantly in the so-called borderzones or watershed regions, which are areas in the brain bordering major vascular territories.

13. Clinical picture
Middle Cerebral Artery MCA stroke:
In general MCA occlusion causes:
Contralateral weakness, sensory loss, homonymous hemianopia.
Language disturbance or impaired spatial perception (depending on the hemisphere involved).

14. (3) Posterior Cerebral Artery Contralateral homonymous hemianopia
(2) Anterior Cerebral Artery
In general ACA infarction causes:
Weakness, clumsiness, and sensory loss affecting mainly the distal contralateral leg.
Urinary incontinence,
Speech disturbance (supplementary motor area)
(3) Posterior Cerebral Artery
Contralateral homonymous hemianopia
Occlusion of PCA trunk (proximal): Structures affected: Thalamus or midbrain

15. Cortical blindness

16. (4) Internal Carotid Artery
In general it clinically may be silent or cause massive cerebral infarction (depending on collateral circulation).

17. Syndromes of infarction
Lateral Medullary Infarction (Due to occlusion of vertebral artery or less often, the posterior inferior cerebellar artery)
Manifestations :( according to nuclei involved)
Vestibular nuclei =causes vertigo, nausea, vomiting and nystagmus.
Cerebellum or inferior cerebellar peduncle =causes gait and ipsilateral limb ataxia
Spinal tract and nucleus of the trigeminal nerve =causes impaired pain and temperature sensation on the ipsilateral face the contralateral body (spinothalamic tract);
Nucleus ambiguous =causes dysphagia, hoarseness, and ipsilateral weakness of the palate and vocal cords and decrease of the gag reflex
Descending sympathetic fibers =causes ipsilateral Horner syndrome.

18. Infarction of Medial Medulla
Due to infarction of the medial medulla usually follows an occlusion of a vertebral artery or a branch of the lower basilar artery and involves the pyramidal tract, medial lemniscus, and hypoglossal nucleus or outflow tract.
Manifestation:
Ipsilateral tongue weakness with deviation toward the paretic side
Contralateral hemiparesis and
Impaired proprioception

19. Lateral Pontine Infarction
Caudal structures affected (due to occlusion of the anterior inferior cerebellar artery).
Middle cerebellar peduncle-ipsilateral ataxia
Vestibular nuclei-vertigo
Trigeminal nucleus-ipsilateral decreased pain and temp.
Spinothalamic tract-contralateral body decreased pain and temp.
Descending symp.fibers-ipsilateral horner.
Rostral structures affected (occlusion of the superior cerebellar artery)
Sup.cerebellar peduncle and cerebellum-ipsilateral ataxia.

20. Medial Pontine Infarction Syndromes
Foville’s syndrome: Contralateral weakness and dysarthrea, ipsilateral face weakness, ipsilateral horizontal gaze palsy
Millard Gubler syndrome: Contralateral weakness and dysarthrea and ipsilateral face weakness.
Pontine wrong way eyes: Contralateral weakness ,ipsilateral horizontal gaze palsy and dysarthrea

21. Midbrain Infarction(occlusion of the posterior cerebral artery)
Weber syndrome (oculomotor palsy with contralateral hemiparesis)
Benedikt syndrome(crossed hemiataxia and chorea)

22. LACUNAR STROKES
Definition: Lacunar strokes are syndromes associated with discrete occlusion of penetrating arterioles (less than 500 µm diameter)
Causes:
most frequently due to sustained hypertension and causing cystic degeneration of brain due to tissue infarction.
Presentation:
1) Silent with no meaningful symptoms.
2) Symptomatic: depend on the location of the small infarcts accordingly there are lacunar syndromes as the following:
Pure motor hemiplegia, seen with infarcts involving the corticospinal tracts in the internal capsule or the pons.
Pure hemisensory stroke, due to involvement of the ascending sensory fibers( a common site is sensory nuclei of the thalamus) in pattern as the pure motor lacunar stroke;
Ipsilateral ataxia and hemiparesis; and the
dysarthria-clumsy-hand syndrome.
Prognosis:
Prognosis for the lacunar syndrome is good, esp. expected hypertension is controlled.
Multiple lacunar infarcts, (whether symptomatic or silent) are correlate with diabetes mellitus, leukoaraiosis or dementia.

23. Work up for stroke
The following diagnostic studies should be done for patient with suspected acute ischemic stroke
For all patients
Noncontrast brain CT
Blood glucose
Serum electrolytes/renal function tests
ECG
Markers of cardiac ischemia
Complete blood count, including platelet count
Prothrombin time/international normalized ratio (INR)
Activated partial thromboplastin time
Oxygen saturation

24. Further investigations be followed to complete stroke work up (esp
Further investigations be followed to complete stroke work up (esp. to what help for secondary prevention and follow up):
MRI Brain
MRA Head and Neck
Carotid Doppler Ultrasound
4- Vessel Angiography

25. Special investigation are mandatory for stroke in young adult (15-45 year old), these include:
Thrombophilia profile
Factor Five liden
Protein S
Protein C
Antithrombin 3ANTITHROMBIN 3
Homocystine level
Lupus anticoagulant
Vasculitic Profile
Anti-phospholipid antibodies
Anti-cardiolipine

26. Management of ischaemic stroke
(1) Acute treatment ( Intravenous Thrombolysis)
Intravenous Recombinant Tissue Plasminogen Activator (rtPA
Candidate patient: every patient fulfills the criteria in table below.
Dosage: 0.9 mg/kg IV, maximum 90 mgI (give 10% of the dose as a bolus then infuse the remainder dose over 60 minutes)
Time be administered: within 4.5 hours of symptom
Major risk of treatment by thrombolytic agent:
Symptomatic brain hemorrhage,( in 6.4% of patients treated with rtPA compared to 0.6% of patients with placebo)
Other potential adverse experiences include systemic bleeding, myocardial rupture if the agent is given within a few days of acute myocardial infarction, and reactions such as anaphylaxis or angioedema, although these events are rare

28. Anti-platelets (used in most patients) Aspirin
(2) Secondary prevention
The most important medical point in prevention of recurrent stroke is the modifying of risk factors
Anti-platelets (used in most patients)
Aspirin
Significant reduction of recurrent stroke(25% reduction in incidence)
In dose:325mg per day
Dipyridamole
Used in combination with aspirin: twice as effective as aspirin alone
Dose: 75mg four times a day(or extended release form 200mg twice daily .
Ticlopidine
Considered with 10% RR reduction over Aspirin
Not used widely in practice because of S/E(almost reversible with discontinuation of drug) include diarrhea(12%), rash, eutropenia (2% and TTP
Used in dose: 250 mg twice a day.
Clopidogrel (Platelet ADP receptor antagonist)
Platelet effects lasts for the lifetime of the platelet (~7-10 days).
Used in dose: 75mg a day
Superior to aspirin for secondary prevention ( debate issue )
Used as alternative for patients who cannot tolerate aspirin

29. the addition of aspirin to clopidogrel increases the risk of hemorrhage and is not routinely recommended for ischemic stroke or TIA patients
 Anticoagulants
Atrial fibrillation with prior transient ischemic attack or stroke
Cardio-embolic stroke
Oral anticoagulants are initiated within 2 weeks, for patients with large infarcts or uncontrolled hypertension, further delays may be appropriate.

30. Anti-lipid
According to Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study (SPARCL) improve the outcome of stroke
2.4 Carotid artery stenosis:
For patient symptomatic carotid stenosis (e.g patient who have had storke or TIA secondery to carotid disease)

31. Transient Ischemic Attack
TIA was originally defined as a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, caused by a transient decrease in blood supply.
This "classic" definition of TIA is inadequate because even relatively brief ischemia can cause permanent brain injury. Furthermore, about one-half of patients with classically defined TIA syndromes (<24 hours in duration) have corresponding appropriate ischemic lesions by brain MRI on diffusion-weighted or perfusion-weighted imaging.

32. Transient ischemic attack (TIA) is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. This tissue-based definition of TIA relies on the absence of end-organ injury as assessed by imaging or other techniques. 

33. The ABCD2 score may identify patients at high risk of ischemic stroke in this time period. The ABCD2 score is tallied as follows:
Age (≥60 years = 1 point)
Blood pressure elevation when first assessed after TIA (systolic ≥140 mmHg or diastolic ≥90 mmHg = 1 point)
Clinical features (unilateral weakness = 2 points; isolated speech disturbance = 1 point; other = 0 points)
Duration of TIA symptoms (≥60 minutes = 2 points; 10 to 59 minutes = 1 point; <10 minutes = 0 points)
Diabetes (present = 1 point)

34. Estimated two-day stroke risks determined by the ABCD2 score in the combined derivation and validation cohorts were as follows [26]:
Score 6 to 7: High two-day stroke risk (8 percent)
Score 4 to 5: Moderate two-day stroke risk (4 percent)
Score 0 to 3: Low two-day stroke risk (1 percent)

35. Spontaneous intracerebral hemorrhage:
Intracerebral hemorrhage (ICH) is the second most common cause of stroke, trailing only ischemic stroke in frequency .
Etiologies — Hypertensive vasculopathy is the most common etiology of spontaneous ICH. Cerebral amyloid angiopathy is the most common cause of nontraumatic lobar ICH in the elderly, while vascular malformations are the most common cause of ICH in children .Additional causes of nontraumatic ICH include:
Hemorrhagic infarction (including venous sinus thrombosis)
Septic embolism, mycotic aneurysm
Brain tumor
Bleeding disorders, anticoagulants, thrombolytic therapy
Central nervous system (CNS) infection (eg, herpes simplex encephalitis)
Moyamoya
Vasculitis
Drugs (cocaine, amphetamines

36. Hypertensive hemorrhages occur in the territory of penetrator arteries that branch off major intracerebral arteries.
These vessels supply the pons and midbrain (penetrators off the basilar artery), thalamus (thalamostriate penetrators off the P1 and P2 segments of the posterior cerebral arteries), and putamen and caudate (lenticulostriate penetrators off the M1 segment of the middle cerebral artery).

37. Mechanisms of brain injury 
Primary direct mechanical injury to brain parenchyma by the expanding clot
Increased intracranial pressure (ICP)
Herniation secondary to mass effect
Risk factors — Hypertension is the most important risk factor for the development of intracerebral hemorrhage (ICH) risk factors for ICH:
Older age
High alcohol intake
Black ethnicity
Lower cholesterol and lower LDL cholesterol
Lower triglycerides
Antithrombotic therapy 

38. Headache, vomiting, and a decreased level of consciousness develop if the hematoma becomes sufficiently large.
Headache may be due to traction on meningeal pain fibers, increased intracranial pressure (ICP), or blood in the cerebrospinal fluid (CSF); it is most common with cerebellar and lobar hemorrhages.
Patients may complain of a stiff neck and have meningismus on physical examination, if there is intraventricular blood.
Seizures

39. EVALUATION AND DIAGNOSIS The acute evaluation of patients with suspected stroke, including issues related to the history, physical examination, airway and breathing, and immediate laboratory studies, were discussed.
Head CT:  CT can define the size and location of the hematoma. It also provides information about extension into the ventricular system, the presence of surrounding edema, and shifts in brain contents (herniation).
Underlying etiology 
 Contrast-enhance MRI
Evaluation for a bleeding disorder

40. General management issues 
Sources of fever should be treated
Hyperglycemia in the first 24 hours after stroke is associated with adverse outcomes
Prevent DVT
Early mobilization and rehabilitation are suggested in patients with ICH who are clinically stable.
Reversal of anticoagulation .
Intracranial pressure control .
Blood pressure control .
Seizure prophylaxis and treatment : 2010 guidelines recommend against prophylactic use of AEDs

41. Surgery For patients with cerebellar hemorrhages >3 cm in diameter who are deteriorating or who have brainstem compression and/or hydrocephalus due to ventricular obstruction, we recommend surgical removal of hemorrhage. S urgery for supratentorial ICH is controversial
Secondary prevention Treating hypertension is the most important step to reduce the risk of ICH, and probably recurrent ICH.
The prognosis after ICH depends upon the location of hemorrhage (supra versus infratentorial location), size of the hematoma, level of consciousness, patient age, and overall medical health.

42. ICH score — A simple six-point clinical grading scale called the ICH score has been devised to predict mortality after ICH [44].
Thirty-day mortality rates increased steadily with ICH score.
The ICH score is determined by adding the score from each component as follows:
Glasgow Coma Scale (GCS) score 3 to 4 (= 2 points); GCS 5 to 12 (= 1 point) and GCS 13 to 15 (= 0 points)
ICH volume ≥30 cm3 (= 1 point), ICH volume <30 cm3 (= 0 points)
Intraventricular extension of hemorrhage present (= 1 point); absent (= 0 points)
Infratentorial origin yes (= 1 point); no (= 0 points)
Age ≥80 (= 1 point); <80 (= 0 points).

43. . Hemphill J C et al. Stroke 2001;32:891-897
Copyright © American Heart Association

44. Possible symptoms and signs?

45. 62 yr old f pt with a history of HTN and AF, awoke early one morning with headache, fell at the doorway when she tried to walk to bathroom, she has left sided weakness and she believed nothing was wrong, no blink to threat on the left and no voluntary gaze to the left, left plantar response was up going and no response to pinprick to on the left side.
On the basis of the symptoms and signs shown , where is the lesion?
What is the most likely diagnoses?

46. Is this patient a candidate for tPA? Treatment?