Hypoxic Ischemic Encephalopathy

The Big Heart Disease Lie

How I Healed my Cardiovascular Disease

Get Instant Access


4 NMDA receptor



Post-synaptic ur necrotic cell death ne U TO n

Excitotoxic mechanisms in the neuron and astrocyte. In the neuron, glutamate is released from the pre-synaptic terminal into the synaptic cleft. The glutamate binding to NMDA receptors allows entry of Ca2+ into the postsynaptic neuron, which can result in necrotic cell death or apoptosis. The glutamate binding to non-NMDA receptors allows entry of Na+ into the post-synaptic neuron, resulting in cytotoxic edema of the neuron. Re-uptake of extracellular glutamate takes place at the pre-synaptic terminals and in adjacent astrocytes.Similar mechanisms also cause cytotoxic edema in the astrocyte with cytotoxic edema of various diseases, including infarction, hypoxic ischemic encephalopathy, status epilepticus, and traumatic brain injury, such as diffuse axonal injury, contusion and shaken baby syndrome [6, 7]. Increased extracellular glutamate is a direct cause of excitotoxic brain injury. In acute exci-totoxic injury, increased extracellular glutamate results from an increased release/ leakage of glutamate or a decreased re-uptake (Fig. 4.5). Neuronal glutamate is released from the pre-synaptic terminal into the synaptic cleft. The glutamate binding to N-methyl-D-aspartate (NMDA) receptors allows entry of Ca2+ into the post-synaptic neuron, which results in necrotic cell death or apoptosis. The glutamate binding to non-NMDA receptors allows entry of Na+ into the post-synaptic neuron, resulting in cytotoxic edema. Apoptosis is defined as a programmed cell death and is histologically characterized by fragmentation of DNA in the nucleus of the cell. Re-uptake of extracellular glutamate takes place at the pre-synap-tic terminals and in adjacent glial cells, which may cause cytotoxic edema (acute phase of reactive astro-cytosis).

Whatever the cause, cytotoxic edema can result in necrosis or delayed neuronal death, or degeneration similar to apoptosis with various amounts of reactive gliosis. Whether necrosis or apoptosis ensues, it may neurochemically depend on the levels of adenosine triphosphate or cytosol calcium ions that trigger protease and lipase production [8].

4.4 Diffusion-Weighted Imaging and Cytotoxic Edema

Cytotoxic edema characteristically shows hyperin-tensity on DW images associated with decreased apparent diffusion coefficient (ADC). The precise mechanisms underlying the reduction in ADC are unknown. The most common explanation is a shift of extracellular water to the intracellular space. However, the observed 40% reduction of ADC cannot be explained by an increase in intracellular water alone, even if all extracellular fluid went intracellular [9]. There must be a reduction in diffusivity of water molecules in the intracellular space which may be explained by the large number of intracellular organelles, that may act as obstacles for diffusion. A decrease in intracellular ADC could also be due to a decrease in the energy-dependent intracellular circulation or an increase in cytoplasmic viscosity from a swelling of intracellular organelles [10].

Tumors, hemorrhages, abscesses and coagulative necrosis also result in a decrease in ADC. The mechanisms underlying the reduction in ADC in those lesions are also unknown, but can be related to hyper-cellularity or hyperviscosity of the pathological tissue [11,12].

4.4.1 Conditions that Cause Cytotoxic Edema, and Reversibility

Cytotoxic edema of neuron and glial cells may accompany infarction [13-16], hypoxic ischemic encephalopathy [17,18],traumatic brain injury [19,20], status epilepticus [6, 21, 22], encephalitis [23] and Creutzfeldt-Jakob disease [24,25].

Neurons and glial cells are the cells most vulnerable to ischemia and hypoxia, but if the ischemia is severe, myelin sheaths and axons may also be involved [3]. These differences among cell types for cytotoxic edema can explain the different time courses of DW abnormalities between gray and white matter in cerebral infarction and hypoxic ischemic encephalopa-thy. In arterial infarction, the area of cytotoxic edema

Ischemia With Edema
Figure 4.6 a-e

Hyperacute cerebral infarction (3 h after onset) in a 39-year-old woman with decreased consciousness. Her neurologic functions improved after intra-arterial thrombolytic therapy.aT2-weighted image appears normal.b DW image shows a hyperintense lesion in the right corona radiata (arrow) and a slightly hyperintense lesion in the right middle cerebral artery (MCA) territory,which may correspond to ischemic penumbra (arrowheads). c ADC map shows a definite decrease in ADC in the corona radiata and slightly decreased ADC in the right MCA territory (arrowheads).d On DW image after fibrinolytic therapy (3 days after onset),the hyperintense lesion in the cortical area is largely resolved,with remaining small, peripheral infarcts. Early cytotoxic edema with slightly decreased ADC does not always result in infarction. e Another case. Pathological specimen of cytotoxic edema in the cortex in an acute stroke shows swelling of neurons (arrows) and glial cells (arrowheads) (hematoxylin-eosin stain,original magnification x200).(From [36])

Hypoxic Ischemic Encephalopathy
Figure 4.7 a-d

A 2-day-old term girl with hypoxic ischemic encephalopathy due to perinatal hypoxia-ischemia event. a T2-weighted image appears normal. b DW image shows hyperintense lesions in the temporo-occipital gray and white matter including the corpus callosum (arrows).Low intensity in bilateral frontal deep white matter (arrowheads) is a normal finding in a patient of this age.c ADC map shows these lesions as decreased ADC representing cytotoxic edema. Increased ADC in the frontal deep white matter is also a normal finding in a patient of this age.These ischemic lesions are more clearly seen on DW imaging than on the ADC map because DW imaging depicts subtle T2 contrast abnormalities (T2 shine-through effect) in addition to the contrast of diffusion restriction of these lesions on DW imaging seems to be irreversibly damaged tissue, resulting in coagulative or liquefactive necrosis. However, mild decreased ADC in the ischemic penumbra can be reversible after intra-arterial or intravenous fibrinolytic therapy (Fig. 4.6). In transient ischemic attacks and venous infarctions, an initially abnormal signal on DW imaging has occasionally been reversed, partially or completely, on follow-up MR images. Hypoxic ischemic encephalopathy (Fig. 4.7) and traumatic brain injury are usually related to irreversible brain damage.

In status epilepticus, cytotoxic edema is often reversed, partially or completely, but may result in selective necrosis, brain atrophy or gliosis (Fig. 4.8). A cytotoxic edema of reactive astrocytes in the acute phase can be responsible for the reversible signal abnormalities [6].

In Creutzfeldt-Jakob disease, the area of cytotoxic edema will eventually develop into prominent brain atrophy (Fig. 4.9). Axonal swelling can also accompany diffuse axonal injury (Fig. 4.10) and the early phase of wallerian degeneration (Fig. 4.11) [26].

Intramyelinic edema may accompany the acute phase of multiple sclerosis (Fig. 4.12) [27,28],toxic or metabolic leukoencephalopathy (Fig. 4.13) [29-31] and osmotic myelinolysis [32]. Partially or completely reversible lesions are also seen in these diseases. The explanation for this reversibility may be an in-tramyelinic edema where the edema is often primarily located in the intramyelinic cleft [1].

Status epilepticus in a 2-year-old girl 24 hours after onset. a T2-weighted image shows diffuse cortical hyperintensity in the entire left hemisphere cortex. b DW image shows diffuse hyperinten-sity mainly in the gray matter of the left hemisphere. c ADC map shows decreased ADC of these lesions. d Diffuse brain atrophy and hyperintense lesions in the left hemisphere are seen on a 5-month follow-up T2-weighted image

Creutzfeldt Jakob Dementia

Creutzfeldt-Jakob disease in a 72-year-old woman with progressive dementia. a T2-weighted image demonstrates mildly increased signal bilaterally in the caudate nuclei and putamina (arrows). b DW image clearly demonstrates bilateral, symmetrical increase in signal intensity in the caudate nuclei and putamina. c ADC map shows these lesions as decreased ADC. d 4-month follow-up MRI shows prominent brain atrophy. (From [37])

Cytotoxic Edema

Figure 4.10 a-c

Diffuse axonal injury in an 18-year-old female 48 h after motor vehicle accident. a T2-weighted image shows mildly hyperintense lesions in the corpus callosum and the white matter of bilateral frontal lobes (arrows). b DW image demonstrates diffuse axonal injury as high signal intensity,repre-senting cytotoxic edema (arrows). c ADC map shows decreased ADC lesions in the anterior to posterior corpus callosum and the frontal deep white matter (arrows). (From [37])

Corpus Callosum Gliosis

Was this article helpful?

0 0
Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

Get My Free Ebook


  • albert
    How does status epilepticus causes hypoxicischemic encephalopathy?
    7 years ago

Post a comment