STROKE

http://stroke.ahajournals.org/content/early/2013/05/07/STR.0b013e318296aeca.full.pdf+html

Table 1. Definition of Stroke
The term “stroke” should be broadly used to include all of the following: Definition of CNS infarction: CNS infarction is brain, spinal cord, or retinal
cell death attributable to ischemia, based on
1. pathological, imaging, or other objective evidence of cerebral, spinal cord,
or retinal focal ischemic injury in a defined vascular distribution; or 2. clinical evidence of cerebral, spinal cord, or retinal focal ischemic
injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded. (Note: CNS infarction includes hemorrhagic infarctions, types I and II; see “Hemorrhagic Infarction.”)

Definition of ischemic stroke: An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. (Note: Evidence of CNS infarction is defined above.)

Definition of silent CNS infarction: Imaging or neuropathological evidence of CNS infarction, without a history of acute neurological dysfunction attributable to the lesion.

Definition of intracerebral hemorrhage: A focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma.
(Note: Intracerebral hemorrhage includes parenchymal hemorrhages after CNS infarction, types I and II—see “Hemorrhagic Infarction.”)

Definition of stroke caused by intracerebral hemorrhage: Rapidly developing clinical signs of neurological dysfunction attributable to a focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma.

Definition of silent cerebral hemorrhage: A focal collection of chronic blood products within the brain parenchyma, subarachnoid space, or ventricular system on neuroimaging or neuropathological examination that is not caused by trauma and without a history of acute neurological dysfunction attributable to the lesion.

Definition of subarachnoid hemorrhage: Bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord).

Definition of stroke caused by subarachnoid hemorrhage: Rapidly developing signs of neurological dysfunction and/or headache because of bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord), which is not caused by trauma.

Definition of stroke caused by cerebral venous thrombosis: Infarction or hemorrhage in the brain, spinal cord, or retina because of thrombosis of a cerebral venous structure. Symptoms or signs caused by reversible edema without infarction or hemorrhage do not qualify as stroke.

Definition of stroke, not otherwise specified: An episode of acute neurological dysfunction presumed to be caused by ischemia or hemorrhage, persisting ≥24 hours or until death, but without sufficient evidence to be classified as one of the above. 

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Stroke is classically characterized as a neurological deficit attributed to an acute focal injury of the central nervous system (CNS) by a vascular cause, including cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), and is a major cause of disability and death worldwide. 


The current World Health Organization definition of stroke (introduced in 1970 and still used) is “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin.”  


In 2009, an expert committee of the AHA/ASA published a scientific statement defining TIA and recommending evaluation. The definition proposed was “transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction.” 


Based on advances including modern brain imaging, the 24-hour inclusion criterion for cerebral infarction is inaccurate and misleading, because permanent injury can occur much sooner.  

However, the location and extent of infarction is one variable to consider when choosing treatment. 

The word “transient” indicates a lack of permanence.    

Modern brain imaging has shown that many patients in whom symptoms and signs of brain ischemia are clinically transient have evidence of brain infarction. If the ischemia caused death of the tissue, it is misleading to designate the ischemia as transient. Similarly, ischemia may produce symptoms and signs that are prolonged (and so qualify in older definitions as strokes), and yet no permanent brain infarction has occurred. 


Knowledge of neuroanatomy and vascular anatomy is important for the clinical diagnosis of stroke and transient CNS ischemia. Brain injuries attributable to vascular causes are nearly always focal, unless they lead to increases in intracranial pressure that cause global cerebral hypoperfusion, as in SAH, or massive infarcts and ICHs.  

During clinical diagnosis, 3 questions require an answer: (1) Is the process vascular or a stroke-like mimic? If a vascular process, then (2) where in the CNS is the abnormality, and which blood vessels supply that area? and (3) What is the disease mechanism (e.g., ischemia or hemorrhage)? 



Retinal infarction is a clinical diagnosis in a patient with acute painless visual loss, typically associated with ischemic whitening of the retina observed on funduscopic examination. A “cherry red spot” may be evident in the macula in patients with central retinal artery occlusion. Retinal infarction rarely requires additional testing to confirm the diagnosis, although occasionally fluorescein angiography is used in atypical cases. 

Radiographic Diagnosis    


Traditional ideas that a strict brain time window exists for acute stroke differ from modern imaging findings obtained by methods such as MRI diffusion-weighted imaging (DWI), which highlights tissue changes after several minutes to days after transient or permanent ischemic events.12,13 A recent Cochrane review of CT and MRI for the diagnosis of acute cerebral infarction within 12 hours of symptom onset showed that the pooled estimates for CT sensitivity and DWI MRI sensitivity were 0.39 and 0.99, respectively, using a clinical diagnosis as the reference standard.


Today, attention is focused on multisequence use of rapid MRI as a biomarker for acute identification of permanent tissue injury as well as viable tissue at risk, widely known as the penumbra.15 Multimodal magnetic resonance angiography, DWI, fluid-attenuated inversion recovery (FLAIR), and perfusion-weighted MRI are used to detect “mismatch,” which identifies the area of potentially reversible injury.  


The use of all of these imaging studies is based on the underlying hypothesis that if the blood supply is not restored, the penumbra will succumb to permanent injury eventually and result in a negative clinical outcome.  

Pathology   


The histopathological criteria for recognizing acute irreversible ischemic neuronal injury (necrosis) have been recognized for decades: An affected neuron loses its basophilic cytoplasm (the result of Nissl substance, or rough endoplasmic reticulum) and prominently nucleolated nucleus, which are replaced by a neuronal cell body showing brightly eosinophilic neuronal cytoplasm lacking identifiable substructure, and a pyknotic or collapsed nucleus; the tinctorial change in the cytoplasm may precede nuclear change (Figure 1).  

A, Subacute cerebral infarction involving left cerebral hemisphere (indicated by arrowheads) that had occurred ≈3 to 4 days before death. Note the pronounced cerebral edema with left-to-right shift of midline structures, including subfalcine herniation of the cingulate gyrus, and marked central diencephalic herniation. 

C, Old cystic cerebral infarcts (observed at autopsy) in 2 different patients. Brain at left shows appearance of left cerebral hemisphere immediately after calvarium has been removed. Arrowheads indicate a large cavity in the middle cerebral artery territory. Brain (coronal section) at right shows a large right MCA territory infarct (indicated by arrowheads) in a patient who had experienced stroke many years previously.  

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The timing of the neuroimaging in relation to the onset of ischemia may impact whether imaging evidence of stroke is seen, since signs of ischemia on noncontrast head CT are seen within the first few hours of CNS infarction in 31% to 60% of cases.45–48 Therefore, within the first 12 hours of an acute stroke, a tissue-based diagnosis of CNS infarction is not possible with the use of routine noncontrast head CT alone but could be if MRI were widely used. Because noncontrast head CT remains the most commonly used imaging modality in the acute setting,49 a patient may have a clear clinical vascular syndrome supporting a diagnosis of CNS infarction but not meet a tissue-based definition of CNS infarction if only CT is used. 

Although the duration of ischemia is important in both focal and global ischemia, focal ischemia is acutely treated with reperfusion strategies to improve flow in an artery. In distinct contrast, global ischemia is acutely treated by correcting the systemic disorder that is the underlying cause of hypo perfusion   


The evaluation of patients with focal and global ischemia also differs. Focal ischemia typically requires assessment of the cervical and cerebral arteries, investigation of a possible cardiac source of emboli, and evaluation of risk factors for atherosclerosis, whereas the evaluation of global ischemia is focused on identifying the underlying cause of hypo perfusion. 


Patients with focal ischemia present with neurological deficits that are localizable to a particular vascular distribution and rarely have a depressed level of consciousness.

However, patients with global ischemia    most commonly present with diffuse nonfocal neurological symptoms, particularly diminished consciousness. The prognosis also differs between focal and global ischemia, because mortality for focal ischemia is ≈12%,56 while for global ischemia >80% of patients do not survive hospitalization, with two thirds of the deaths attributable to neurological injury.

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The brain, spinal cord, and retina derive from neural tube tissue and therefore constitute the CNS, while the cranial and peripheral nerves derive from neural crest tissue.62 There are differences in the mechanisms of ischemia, treatment, and recovery between CNS and peripheral nervous system (PNS) ischemia that warrant limitation of the definition of infarction to the CNS.  


CNS ischemia, as previously described, results from stenosis or occlusion of both large vessels and small vessels attributable to local thrombosis or embolization from other vascular regions or from critical hypoperfusion in border-zone regions. PNS ischemia typically results from small-vessel occlusion of the vasa nervorum presenting as mononeuropathies, most commonly related to vasculitis or diabetes mellitus. 


For CNS ischemia, the treatment is focused on establishing reperfusion in the acute setting and then secondary prevention of ischemia. For PNS ischemia, treatments are focused on the underlying condition (ie, steroids for vasculitis or glucose control for diabetes mellitus), and acute reperfusion treatments are not available. The CNS and PNS also differ with respect to potential for recovery after ischemic injury. The PNS has a greater regenerative capacity than the CNS because of innate differences between the neurons and supportive cells in these locations, allowing for PNS axonal regeneration after injury.