Sandbox:AA

# Differential diagnosis of bacterial meningitis

# classification of bacterial meningitis
Prevention of stroke can work at various levels including:
- primary prevention - the reduction of risk factors across the board, by public health measures such as reducing smoking and the other behaviours that increase risk;
- secondary prevention - actions taken to redrombuce the risk in those who already have disease or risk factors that may have been identified through screening; and
- tertiary prevention - actions taken to reduce the risk of complications (including further strokes) in people who have already had a stroke.
The most important modifiable risk factors for stroke are hypertension, heart disease, diabetes, and cigarette smoking. Other risks include heavy alcohol consumption (see Alcohol consumption and health), high blood cholesterol levels, illicit drug use, and genetic or congenital conditions. Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Higher levels of Von Willebrand factor are more common amongst people who have had ischemic stroke for the first time. The results of this study found that the only significant genetic factor was the person's blood type. Having had a stroke in the past greatly increases one's risk of future strokes.
One of the most significant stroke risk factors is advanced age. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65. A person's risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in fetuses.
Sickle cell anemia, which can cause blood cells to clump up and block blood vessels, also increases stroke risk. Stroke is the second leading killer of people under 20 who suffer from sickle-cell anemia.
Men are 1.25 times more likely to suffer strokes than women, yet 60% of deaths from stroke occur in women. Since women live longer, they are older on average when they have their strokes and thus more often killed (NIMH 2002). Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause and the treatment thereof (HRT).
Prevention is an important public health concern. Identification of patients with treatable risk factors for stroke is paramount. Treatment of risk factors in patients who have already had strokes (secondary prevention) is also very important as they are at high risk of subsequent events compared with those who have never had a stroke. Medication or drug therapy is the most common method of stroke prevention. Aspirin (usually at a low dose of 75 mg) is recommended for the primary and secondary prevention of stroke.  Also see Antiplatelet drug treatment.  Treating hypertension, diabetes mellitus, smoking cessation, control of  hypercholesterolemia, physical exercise, and avoidance of illicit drugs and excessive alcohol consumption are all recommended ways of reducing the risk of stroke.
In patients who have strokes due to abnormalities of the heart, such as atrial fibrillation, anticoagulation with medications such as warfarin is often necessary for stroke prevention.
Procedures such as carotid endarterectomy or carotid angioplasty can be used to remove significant atherosclerotic narrowing (stenosis) of the carotid artery, which supplies blood to the brain. These procedures have been shown to prevent stroke in certain patients, especially where carotid stenosis leads to ischemic events such as transient ischemic attack. (The value and role of carotid artery ultrasound scanning in screening has yet to be established.)
A meta-analysis concluded that lowering homocysteine with folic acid and other supplements may reduce stroke. However, the two largest randomized controlled trials included in the meta-analysis had conflicting results. Lonn reported positve results; whereas the trial by Toole was negative.
Aysha's sandbox
TOAST CLASSIFICATION OF Acute ISCHEMIC STROKE:
- Large artery atherosclerosis
- Cardioembolism
- Small vessel occlusion-Lacunar infarct
- Stroke of other, unusual, determined etiology
- Stroke of undetermined etiology
Based on duration of symptoms:
- Transient ischemic stroke
- Acute ischemic stroke
- Chronic ischemic stroke:
Ischemic stroke due to cause:
- Artherosclerotic
- Non Artherosclerotic
- Systemic hypoperfusion
PATHOPHYSIOLOGY:
Hemodynamic changes:
- Reduction in blood flow due to systemic hypoperfsuion, involves watershed areas
hippocampal pyramidal cells, cerebellar Purkinje cells, and cortical laminar cells
- Thrombosis acutely or chronically, involves extrascranail and intracranial vesssels. Atherosclerotic blood vessels , plts adhere to plaque causing occlusion
- Embolic stroke: clot foms elsewhere in the body and travels to the brain, usually heart in afib, other emboli causing stroke involves tumour, septic embolus, venous clot or fat
- Embolic stroke-cortical undergo hemorrhagic transformation
- Lacunar infarction: involves small penetrating vessels, chronic hypertension causes thickening of media and fibrinoid depositon in the vessel wall causing lumen narrowing and occlusion.
Ususally subcortical but any site can be involved.
Non atherosclerotic causes such as
-Fibromuscular dysplasia 
-Vasculitis
-Moyamoya disease 
-Sickle cell disease arteriopathy 
-Focal cerebral arteriopathy of childhood
Cause      Pathogenesis          area involved
Cellular changes:
- Focal ischemia-area affected by single blood vessel and its surrounding branches. Central core of tissue die by necrosis as directly supplied by the blood vessel, called infarct.
The cells surrounding the central infarct  supplied by collateral vessels receive some oxygen and glucose, at increased risk of infarction but can be salvaged by increase in blood flow to the area called Pneumbra. 
Molecular changes:
- Depletion of ATP
- Acidosis, lactate increased
- Ionic imbalance: Na,K, Ca
- Increase in excitatory neurotrasmittor glutamate at synases due to neuronal electrical failure-
Glutamate receptor stimulation NMDA receptors opening of ion channels, increased calcium and sodium influx and potassium eflux
- Increased Na influx and water-edema and causes decreased uptake of glutamate resulting in excitotoxicity state in the brain
- NMDA receptor activation causes increase NO levels in the brain-excessive levels acts as a free radical-reacts with other free oxygen radicals producing peroxynitirite causing breaks in DNA and DNA damage- Apoptosis
Type of cell death after ischemia
Type of infarct         time of initiation of cell death     Main mechanism of cell death     Area invol
- Global ischemia     delayed after 12 hours several days              Apoptosis                                     Hippoca
- Focal ischemia       Within 3-4 hours -12 to 24hrs                       Necrosis        central core by necrosis and periphery by apoptosis                      centre
Loss of brain structural integrity
Cerebral edema: 
Vasogenic: Disruption of bbb
Celluar/cytotoxic: ATP dep ion regualtion disrupted
Cerebral autoregulation
Cerebral blood flow determinants
- Cerebral perfusion pressure
- Cerebral blood flow is maintained in the pressure range of 60-150 mmg
- Cerebral blood flow increases in cases of low pressure by vasodilation- nitric oxide release by endothelial cells
- Blood flow decreases by vasoconstriction at high pressures. Smooth muscles in the Bv are the sensors for detection of blood vessels
Pressure below 60 mmhg ischemia 
Pressure above 150 mmhg edema
Cerebral autoregulation failure during ischemia:
Low pressures- cerebral vasodilation to increase blood flow-increased oxygen extraction ratio initially to maintain oxygen levels in the brain cells-further dcline in blood presssure- compensatory mechanisms fail-inhibtion of protein synthesis 35ml/100gm/min, increased glucose utilization  25ml/100gm/minanaerobic glycolysis-tissue acidosis-neuronal electric failure16-18ml/100gm/min-cell membrane dysfunctionml/100gm /min 10-12-cell death (infart)
In hypertension autoregulation set at higher pressures so drop to normal levels may exacerbate ischemia
GENETICS:
-HDAC9 for large vessel disease
-ABO for all ischemic stroke
Prognosis of ischemic stroke
1)a)age, stroke severity, stroke mechanism, infarct location, comorbid conditions, clinical findings, and related complication;
b) interventions such as thrombolysis, stroke unit care, and rehabilitation can play a major role in the outcome of ischemic strok
c)acute phase of stroke, the strongest predictors of outcome are stroke severity and patient age.
2):Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, et al. Acute blood glucose level and outcome from ischemic stroke.aird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, et al. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcomeMandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute strokeTissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study GroupAcute stroke: usefulness of early CT findings before thrombolytic therapy
3)Poor prognostic factors:
Severe middle cerebral artery infarction
- Large area of brain involvement
- Other co morbid conditons
- Advanced age
- Severe hemiplegia
4)Good prognostic factors:
5)NIHSS score predicts early mortality predicts prognosis; The NIHSS score strongly predicts the likelihood of a patient's recovery after stroke. A score of > or =16 forecasts a high probability of death or severe disability whereas a score of < or =6 forecasts a good recovery.
6)The 1-year mortality in first-time stroke sufferers is 14% to 24% in persons aged 40 to 69 years, and the 1-year mortality increases to 22% to 27% in patients aged 70 years and older. (Find citation)
CDC
Stroke kills almost 130,000 Americans each yearthats 1 out of every 20 deaths.1
On average, one American dies from stroke every 4 minutes.2
Every year, more than 795,000 people in the United States have a stroke.
About 610,000 of these are first or new strokes.
About 185,00 strokesnearly one of fourare in people who have had a previous stroke.2
About 87% of all strokes are ischemic strokes, when blood flow to the brain is blocked.2
Stroke costs the United States an estimated $34 billion each year.2 This total includes the cost of health care services, medications to treat stroke, and missed days of work.
Stroke is a leading cause of serious long-term disability.2
Classification of Ischemic Stroke:
According to the causative agent:
- Thrombotic
- Embolic
- Small vessel disease
- Systemic hypoperfusion
- Crytogenic-Undetermined etiology
Toast classification of ischemic stroke:
According to anatomical location:
- Cortical
- Subcortical
- Watershed areas
According to vessel involved:
- Anterial cerebral artery
- Middle cerebral artery
- Posterior cerebral artery
According to duration of symptoms:
- Acute
- subacute
- Chronic
According to clinical presentaion
- Pure Motor
- Pure Sensory
- Mixed
Stroke epidemiology PMID: 26673558
In 2013, stroke fell from the fourth to the fifth leading cause
-f death in the United States, behind diseases of the heart,
cancer, chronic lower respiratory diseases, and unintentional
injury.
 From 2003 to 2013, the relative rate of stroke death fell
by 33.7% and the actual number of stroke deaths declined by 18.2%. Yet each year, 795 000 people continue to
experience a new or recurrent stroke (ischemic or hemorrhagic).
Approximately 610 000 of these are first events
and 185 000 are recurrent stroke events. In 2013, stroke
caused 1 of every 20 deaths in the United States. On average,
every 40 seconds, someone in the United States has
a stroke, and someone dies of one approximately every 4
minutes.
 The decline in stroke mortality over the past decades, a
major improvement in population health observed for
both sexes and all race and age groups, has resulted from
reduced stroke incidence and lower case fatality rates. The
significant improvements in stroke outcomes are concurrent
with cardiovascular risk factor control interventions.
The hypertension control efforts initiated in the 1970s
appear to have had the most substantial influence on the
accelerated decline in stroke mortality, with lower blood
pressure distributions in the population. Control of diabetes
mellitus and high cholesterol and smoking cessation
programs, particularly in combination with hypertension
treatment, also appear to have contributed to the decline in
stroke mortality.
 Approximately 10% of all strokes occur in people 18 to
50 years of age. Between 1995 and 2008, National Health
Interview Survey data reveal that hospitalizations for
ischemic stroke increased among adolescents and young
adults (aged 544 years), whereas subarachnoid hemorrhage
hospitalizations decreased during that same time
period.
 Stroke death rates declined more among people aged 65
years (54.1%; from 534.1 to 245.2 per 100 000) than
among those aged 45 to 64 years (53.6%; from 43.5 to
20.2 per 100 000) or those aged 18 to 44 years (45.9%;
from 3.7 to 2.0 per 100 000).

## Common complications
MRI syphilis 17628376
- 20 mg/kg/dose twice daily (max = 500 mg/dose)
- 10 days
- 30 mg/kg once daily (max = 1 g)
- 10 days
- 7 mg/kg/dose 3 times daily (max = 300 mg/dose)
- 10 days
- 12 mg/kg once daily (max = 500 mg)
- 5 days
- 7.5 mg/kg/dose twice daily (max = 250 mg/dose)
- 10 days

## Postexposure prophylaxis

### Active immunisation
Varicella vaccine is recommended for immunocompetent individuals exposed to varicella infection but did not receive full two dose course of vaccine previously

### Passive immunisation
VZV immunoglobulin
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