CEREBROVASCULAR DISEASES RISK FACTORS:

 Prevention of cerebrovascular disease is more likely to reduce death and disability than any medical or surgical
advance in management. Prevention depends upon the identification of risk factors and their correction. Increasing
age is the strongest risk factor (but is not amenable to correction).
 Hypertension:
o Hypertension is a major factor in the development of thrombotic cerebral infarction and intracranial haemorrhage.
o There is no critical blood pressure level; the risk is related to the height of blood pressure and increases
throughout the whole range from normal to hypertensive. A 6 mmHg fall in diastolic blood pressure is associated
in relative terms with a 40% fall in the fatal and non-fatal stroke rate.
o Systolic hypertension (frequent in the elderly) is also a significant factor and not as harmless as previously
thought.
 Cardiac disease
o Cardiac enlargement, failure and arrhythmias, as well as rheumatic heart disease, patent foramen ovale and,
rarely, cardiac myxoma are all associated with an increased risk of stroke.
 Diabetes
o The risk of cerebral infarction is increased twofold in diabetes. More effective treatment of diabetes has not
reduced the frequency of atherosclerotic sequelae.”

ISCHEMIC STROKE
 characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of
neurologic function. Acute ischemic stroke is caused by thrombotic or embolic occlusion of a cerebral artery and is
more common than hemorrhagic stroke.
Diagnostics:
 Emergent brain imaging is essential for evaluation of acute ischemic stroke. Noncontrast computed tomography (CT)
scanning is the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute
stroke. The following neuroimaging techniques may also be used emergently:
o CT angiography and CT perfusion scanning
o Magnetic resonance imaging (MRI)
o Carotid duplex scanning
o Digital subtraction angiography
 Lumbar puncture
o A lumbar puncture is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is negative
but the clinical suspicion remains high
 Laboratory studies
o Laboratory tests performed in the diagnosis and evaluation of ischemic stroke include the following:
 Complete blood count (CBC): A baseline study that may reveal a cause for the stroke (eg, polycythemia,
thrombocytosis, leukemia), provide evidence of concurrent illness, and ensure absence of thrombocytopenia
when considering fibrinolytic therapy
 Basic chemistry panel: A baseline study that may reveal a stroke mimic (eg, hypoglycemia, hyponatremia) or
provide evidence of concurrent illness (eg, diabetes, renal insufficiency)
 Coagulation studies: May reveal a coagulopathy and are useful when fibrinolytics or anticoagulants are to be
used
 Cardiac biomarkers: Important because of the association of cerebral vascular disease and coronary artery
disease
 Toxicology screening: May assist in identifying intoxicated patients with symptoms/behavior mimicking stroke
syndromes or the use of sympathomimetics, which can cause hemorrhagic and ischemic strokes
 Pregnancy testing: A urine pregnancy test should be obtained for all women of childbearing age with stroke
symptoms; recombinant tissue-type plasminogen activator (rt-PA) is a pregnancy class C agent

HEMORRHAGIC STROKE
Intracerebral hemorrhage
 Usually due to hypertension
 Pathologic basis for hemorrhage is probably the presence of microaneurysms that develop on perforating vessels in
hypertensive patients
 Hypertensive intracerebral hemorrhage occurs most frequently in the basal ganglia, pons, thalamus, cerebellum and
less common in the cerebral white matter
 S/sx
o Consciousness is initially lost or impaired in about ½ of patients
o Vomitting occurs very frequently at the onset of bleeding and headache is sometimes present
o With hypertensive hemorrhage, there is generally a rapidly evolving neurologic deficit with hemiplegia or
hemiparesis
o With lesions of the putamen, loss of conjugate lateral gaze may be conspicuous
 o With thalamic hemorrhage, there may be a loss of upward gaze, downward, or skew deviation of the eyes, lateral
gaze palsies, and pupillary inequalities
o Cerebellar hemorrhage may present with sudden onset of nausea and vomiting, disequilibrium, ataxia of gait,
limbs or trunk; headache; loss of consciousness that may terminate fatally within 48 hours
o Pontine hemorrhage causes some combination of lateral conjugate gaze palsies to the side of the lesion; small
reactive pupils; contralateral hemiplegia; peripheral facial weakness; and periodic respiration
From Harrison’s
Hypertensive Intracerebral Hemorrhage
PATHOPHYSIOLOGY
 Hypertensive ICH usually results from spontaneous rupture of a small penetrat-ing artery deep in the brain. The most
common sites are the basal ganglia (especially the putamen), thalamus, cerebellum, and pons. The small arteries in
these areas seem most prone to hypertension-induced vascular injury. When hemorrhages occur in other brain areas
or in nonhypertensive patients, greater consideration should be given to other causes such as hemorrhagic disorders,
neoplasms, vascular mal-formations, and cerebral amyloid angiopathy. The hemorrhage may be small, or a large clot
may form and compress adjacent tissue, causing herniation and death. Blood may also dissect into the ventricular
space, which substantially increases morbidity and may cause hydrocephalus.
 Most hypertensive ICHs initially develop over 30–90 min, whereas those associated with anticoagulant therapy may
evolve for as long as 24–48 h. However, it is now recognized that about a third of patients even with no coagulopathy
may have significant hematoma expansion with the first day. Within 48 h, macrophages begin to phagocytize the
hemorrhage at its outer surface. After 1–6 months, the hemorrhage is generally resolved to a slitlike orange cavity
lined with glial scar and hemosiderin-laden macrophages.
CLINICAL MANIFESTATIONS:
 ICH generally presents as the abrupt onset of a focal neurologic deficit. Seizures are uncommon. Although clinical
symptoms may be maximal at onset, commonly the focal deficit wors-ens over 30–90 min and is associated with a
diminishing level of con-sciousness and signs of increased ICP such as headache and vomiting. The putamen is the
most common site for hypertensive hem-orrhage, and the adjacent internal capsule is usually damaged (Fig. 446-17).
Contralateral hemiparesis is therefore the sentinel sign.
 When mild, the face sags on one side over 5–30 min, speech becomes slurred, the arm and leg gradually weaken,
and the eyes deviate away from the side of the hemiparesis. The paralysis may worsen until the affected limbs
become flaccid or extend rigidly. When hemorrhages are large, drowsiness gives way to stupor as signs of upper
brainstem compression appear. Coma ensues, accompanied by deep, irregular, or intermittent respiration, a dilated
and fixed ipsilateral pupil, and decerebrate rigidity. In milder cases, edema in adjacent brain tissue may cause
progressive deterioration over 12–72 h.
 Thalamic hemorrhages also produce a contralateral hemiplegia or hemiparesis from pressure on, or dissection into,
the adjacent internal capsule. A prominent sensory deficit involving all modalities is usually present. Aphasia, often
with preserved verbal repetition, may occur after hemorrhage into the dominant thalamus, and constructional apraxia
or mutism occurs in some cases of nondominant hemorrhage. There may also be a homonymous visual field defect.
Thalamic hemor-rhages cause several typical ocular disturbances by virtue of extensioninferiorly into the upper
midbrain. These include deviation of the eyes downward and inward so that they appear to be looking at the nose,
unequal pupils with absence of light reaction, skew deviation with the eye opposite the hemorrhage displaced
downward and medially, ipsilateral Horner’s syndrome, absence of convergence, paralysis of vertical gaze, and
retraction nystagmus. Patients may later develop a chronic, contralateral pain syndrome (Déjérine-Roussy syndrome).
 In pontine hemorrhages, deep coma with quadriplegia often occurs over a few minutes. Typically, there is prominent
decerebrate rigidity and “pinpoint” (1 mm) pupils that react to light. There is impairment of reflex horizontal eye
movements evoked by head turning (doll’s-head or oculocephalic maneuver) or by irrigation of the ears with ice water
(Chap. 328). Hyperpnea, severe hypertension, and hyperhidrosis are common. Most patients with deep coma from
pontine hemorrhage ultimately die, but small hemorrhages are compatible with survival
 Cerebellar hemorrhages usually develop over several hours and are characterized by occipital headache, repeated
vomiting, and ataxia of gait. In mild cases, there may be no other neurologic signs except for gait ataxia. Dizziness or
vertigo may be prominent. There is often pare-sis of conjugate lateral gaze toward the side of the hemorrhage, forced
deviation of the eyes to the opposite side, or an ipsilateral sixth nerve palsy. Less frequent ocular signs include
blepharospasm, involuntary closure of one eye, ocular bobbing, and skew deviation. Dysarthria and dysphagia may
occur. As the hours pass, the patient often becomes stuporous and then comatose from brainstem compression or
obstruc-tive hydrocephalus; immediate surgical evacuation before brainstem compression occurs may be lifesaving.
Hydrocephalus from fourth ven-tricle compression can be relieved by external ventricular drainage, but definitive
hematoma evacuation is recommended. If the deep cerebellar nuclei are spared, full recovery is common.
 Lobar Hemorrhage The major neurologic deficit with an occipital hem-orrhage is hemianopia; with a left temporal
hemorrhage, aphasia and delirium; with a parietal hemorrhage, hemisensory loss; and with fron-tal hemorrhage, arm
weakness. Large hemorrhages may be associated with stupor or coma if they compress the thalamus or midbrain.
Most patients with lobar hemorrhages have focal headaches, and more than one-half vomit or are drowsy. Stiff neck
and seizures are uncommon
ENDOMETRIAL CARCINOMA BRAIN METASTASIS
(NCBI, Ettie Piura and Benjamin Piura)
 Endometrial cancer is the most common gynecologic malignancy and accounts for 6% of all cancers in women. An
estimated 43,470 cases are diagnosed with an estimated 7950 deaths in 2010[1]. Endometrial carcinoma is divided
into several histologic categories based on cell type. Endometrioid is the most common cell type, accounting for 75–
80% of cases, and subdivided into grade 1 (well differentiated) to grade 3 (poorly differentiated). Other aggressive
pathologic variants with a high risk of metastatic disease include papillary serous carcinoma (<10%), clear cell
carcinoma (4%), squamous cell carcinoma (<1%), mixed (10%) and undifferentiated types[2].
 brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median
survival after diagnosis of brain metastases from endometrial carcinoma was 5 months
 Female genital tract cancers, however, are considered “neurophobic” since brain metastases from female genital tract
cancers, apart from choriocarcinoma, are rare and usually develop as part of a widespread disseminated disease.
 The primary mechanism of metastatic spread from genital tract cancers to the brain is by the hematogenous rout.
Detached tumor cells are carried from the genital tract by the blood stream through the inferior vena cava, right
atrium, right ventricle, pulmonary artery, lungs, pulmonary veins, left atrium, left ventricle, and aorta to the brain
 Symptoms and signs of brain metastases from endometrial carcinoma are not different from symptoms and signs of
other brain space occupying lesions.
o headache, confusion, dizziness, decreased mental status, consciousness disturbance, general weakness,
extremity weakness, gait disturbance, neurological motor deficit, hemiparesis, ataxia, visual disturbance,
papilledema, incontinence, nausea, vomiting, speech impairment (aphasis), parasthesias, syncope, and
seizure.
o the most common neurologic symptoms were confusion: 9 (45%) patients, gait disturbance: 8 (40%),
paralysis: 4 (20%), speech difficulty: 2 (10%), and nausea and vomiting: 2 (10%)

HYPERGLYCEMIA
 Diabetes is a well-established risk factor for stroke. It can cause pathologic changes in blood vessels at various
locations and can lead to stroke if cerebral vessels are directly affected. Additionally, mortality is higher and
poststroke outcomes are poorer in patients with stroke with uncontrolled glucose levels.

 There are several possible mechanisms wherein diabetes leads to stroke. These include vascular endothelial
dysfunction, increased early-age arterial stiffness, systemic inflammation and thickening of the capillary basal
membrane. Abnormalities in early left ventricular diastolic filling are commonly seen in type II diabetes. The
proposed mechanisms of congestive heart failure in type II diabetes include microvascular disease, metabolic
derangements, interstitial fibrosis, hypertension and autonomic dysfunction (Figure 1). Vascular endothelial
function is critical for maintaining structural and functional integrity of the vessel walls as well as the vasomotor
control. Nitric oxide (NO) mediates vasodilation, and its decreased availability can cause endothelial dysfunction
and trigger a cascade of atherosclerosis. For example, NO-mediated vasodilation is impaired in individuals with
diabetes, possibly due to increased inactivation of NO or decreased reactivity of the smooth muscle to NO.
Individuals with type II diabetes have stiffer arteries and decreased elasticity compared with subjects having
normal glucose level. Type I diabetes is more often associated with an early structural impairment of the common
carotid artery, commonly reflected as increased intima-medial thickness, and is considered as early sign of
atherosclerosis. An increased inflammatory response is frequently seen in individuals with diabetes, inflammation
plays an important role in the development of the atherosclerotic plaque. The C-reactive protein, cytokines and
adiponectin are the main serum markers of inflammation. The C-reactive protein and the plasma levels of these
cytokines including interleukin-1, interleukin-6 and tumor necrosis factor-α are independent predictors of
 cardiovascular risk. Adiponectin appears to be a modulator of lipid metabolism and systemic inflammation. A low
level of adiponectin itself has also been associated with CVD.


 By provoking anaerobic metabolism, lactic acidosis, and free radical production, hyperglycemia may exert direct
membrane lipid peroxidation and cell lysis in metabolically challenged tissue. Moderately and severely increased
blood glucose has been found to further the metabolic state and mitochondrial function in the area of ischemic
penumbra.
 Insulin resistance is a known risk factor for the onset of stroke acting through a number of intermediate vascular
disease risk factors (ie, thrombophilia, endothelial dysfunction, and inflammation).4 The evolution of an acute
infarction may be expedited by the very same vascular factors, explaining why ischemia time seems to fly faster
with patients with diabetesor grave hyperglycemia. Relative insulin deficiency liberates circulating free fatty acids,
which, together with hyperglycemia, reportedly diminishes vascular reactivity. Furthermore, lowering glucose with
insulin has been reported to reduce ischemic brain damage in an animal model.
 The evolution of an infarction is accompanied by glutamate release mediating repeated waves of spreading
depression (SD), another mechanism believed to propagate the necrosis of the penumbral tissue. Although
hyperglycemia alone did not trigger early-response genes in the cortical tissue of rats, in conjunction with induced
SD, the expression of c-fos and cyclooxygenase-2 were substantially increased.8 This suggests that elevated
glucose may trigger untoward intracellular biochemical cascades also by altering early gene expression in
metabolically challenged neurons. The blood-brain barrier is well known to be vulnerable to hyperglycemia,
presumably through the liberation of lactic acid and free radicals. The recent experimental study by Song et al in a
rat model of collagenase-induced intracerebral hemorrhage (ICH) adds that hyperglycemia aggravates edema
formation in a zone surrounding cerebral hemorrhages.9 The study also documented increased cell death
measured by the TUNEL staining. It is conceivable that hemorrhages are surrounded by a zone of similarly
challenged tissue as infarctions are, where the availability of glucose influences the metabolic state

Medscape:
 The specific mechanism(s) by which hyperglycemia leads to poorer clinical outcome in patients receiving
anticoagulants or thrombolytics is not known, although several have been proposed. In some vascular beds,
hyperglycemia causes glycosylation and thereby interferes with protein and enzyme function, including those
functions that regulate production of substances that cause vasodilation and cellular adhesion within the
vasculature. Hyperglycemia results in the formation of advanced glycation end products that are toxic to
endothelial cells, and production of free radicals from various sources may result in further vascular injury.
 Hyperglycemia worsens outcome and increases rate of mortality from stroke. Two mechanisms have been
postulated to explain the negative influence of hyperglycemia on outcome following stroke: (1) poorer reperfusion
due to vascular injury and a loss of vascular tone through oxidation of nitric oxide dependent mechanisms; and (2)
increased acidosis, perhaps from lactic acid/acid sensing channels, leading to further tissue injury. Both
mechanisms have been supported by experimental data.
 Martini and Kent suggest that, even if an occluded vessel causing stroke is recanalized, effective reperfusion may
not be established in patients with hyperglycemia. [17] By setting up a “pro-constrictive, pro-thrombotic and pro-
inflammatory” state, hyperglycemia may be harmful to the endothelial cells and the vascular tree.
 Parsons et al. used magnetic resonance imaging (MRI) and magnetic resonance spectroscopy in patients with
hyperglycemic stroke and reported that the detrimental effect of hyperglycemia may be due to metabolic acidosis
in the infracted brain parenchyma. [18] However, earlier animal studies suggested that hyperglycemia has a
detrimental effect on the cerebral vascular tree. [19, 20]