CNS Diseases: Malformations, Edema & Herniation

• Diseases of the central nervous system (CNS) differ from other organ system disorders due to unique CNS features.
• These unique features include physical constraints within the skull, neuron sensitivity to hypoxia, and neurons' inability to regenerate.
• This chapter focuses on brain diseases, with spinal cord involvement mentioned when relevant, and concludes with a brief discussion of peripheral nerve diseases.

Congenital Malformations of the CNS

• Congenital malformations of the CNS arise from genetic abnormalities, trauma, or other insults.
• CNS malformations can lead to intellectual disability, cerebral palsy, or neural tube defects, affecting 1% to 2% of births.
• Neural tube defects are linked to folate deficiency during the first month of pregnancy.
• Folate supplementation throughout reproductive years is needed for risk reduction.

Cerebral Edema, Herniation, and Hydrocephalus

• These disorders often result from underlying conditions and reflect the anatomical constraints on the brain.
• Cerebral edema involves fluid accumulation in the brain parenchyma.
• Herniation involves brain tissue displacement due to increased intracranial pressure, causing damage by direct compression or blood vessel compression.
• Subfalcine herniation involves the cingulate gyrus being pushed under the falx, potentially compressing the middle cerebral artery.
• Transtentorial (uncinate) herniation has the temporal lobe compressed against the tentorium, leading to pupillary dilation and potential ischemic injury.
• Tonsillar herniation displaces cerebellar tonsils through the foramen magnum, causing brain stem compression and respiratory/cardiac failure.
• Hydrocephalus involves increased cerebrospinal fluid (CSF) volume within the brain's ventricles, typically from obstruction of CSF outflow.
• Noncommunicating hydrocephalus involves dilation of ventricles upstream of the block.
• Communicating hydrocephalus involves defective absorption and affects all ventricles.
• Hydrocephalus ex vacuo arises from brain parenchyma atrophy.
• In infants, hydrocephalus before cranial suture closure can enlarge the head.

Cerebrovascular Diseases

• Cerebrovascular disorders, mainly thromboembolic diseases, cause infarction and hemorrhage.
• Also called stroke, these are a leading cause of death and preventable cause of neurologic morbidity/mortality.
• The brain needs a lot of oxygen.
• Compromised blood supply to the brain causes devastating consequences.

Cerebral Artery Thrombosis, Embolism, and Brain Infarction

• Occlusion of arterial supply leads to liquefactive necrosis, forming an infarct.
• Embolism can stem from the heart or deep vein thrombi, with the middle cerebral artery as the common site.
• Thrombosis superimposed on atherosclerotic plaques can occur at various arterial locations.
• Hypertension-related thrombotic occlusions can lead to lacunar infarcts.
• Global ischemia from severe hypotension can also cause ischemic injury.
• Infarcts are initially nonhemorrhagic and can evolve, especially with restored blood supply.
• Hemorrhagic infarcts have petechial hemorrhages, while nonhemorrhagic infarcts evolve through stages to leave a cystic cavity.
• Ischemic injury in neurons causes cytoplasmic eosinophilia ("red neurons") and edema.
• Neutrophils infiltrate, followed by monocytes and activated astrocytes (reactive gliosis).
• Global ischemia can produce similar microscopic changes.
• Hypotensive episodes can cause watershed infarcts in distal arterial supply areas.
• Manifestations depend on the infarct's location and cerebral edema effects.

Intracranial Hemorrhage

• Hemorrhages in different brain compartments can stem from trauma, hypertension, or structural vessel abnormalities.
• Trauma is a major cause of vascular injury in the brain.
• Epidural and subdural hematomas are almost always secondary to trauma.
• Subarachnoid hemorrhage is often caused by saccular aneurysm rupture or arteriovenous malformation (AVM) rupture.
• Parenchymal hemorrhages are commonly from hypertension, leading to rupture of small arteries.
• Epidural and subdural hematomas involve blood collections in the cranial space, not extending into the brain.
• Hypertensive parenchymal bleeds typically affect basal ganglia, thalamus, pons, and cerebellum, eventually forming cavities with residual hemosiderin.
• Aneurysms are thin-walled outpouchings in the anterior cerebral circulation near arterial branch points and lack a muscular wall.
• AVMs (arteriovenous malformations) are vascular tissue networks.
• Presentation of hemorrhages may have a lucid interval after traumatic epidural bleed.
• Other times there may be sudden, excruciating headache follows aneurysm.

Other Vascular Diseases

• Hypertension and amyloid deposition can cause vascular abnormalities in the CNS.
• Hypertension causes hyaline sclerosis leading to hemorrhages or lacunar infarcts.
• Sudden increases in blood pressure may result in acute hypertensive encephalopathy.
• Cerebral amyloid angiopathy causes hemorrhages and have a relationship to Alzheimer's.

CNS Trauma

• Trauma directed to the brain can cause injury to the parenchyma or blood vessels.
• Coup injuries are ones at the site of impact, while contrecoup injuries are on the opposite side of the brain.
• Concussions are reversible changes in brain function
• Repeated head trauma may result in cognitive defects and neurological problems that leads to encephalopathy.

Perinatal Brain Injury

• Cerebral hemorrhages in infants leads to long-term effects.
• Premature babies in particular are susceptible to hemorrhages, which can result in cerebral palsy and injury.

CNS Infections

• Bacteria, Viruses, and Fungi all have potential to infect the brain tissue causing more complications.
• Pathogens enter the brain through hematogenous spread or direct implantation.
• CSF will show high amounts of protein and other bacteria.

Prion Diseases

• Prions are infectious proteins that cause more damage
• Prions self propagate and cause degeneration of white matter.

Demyelinating Diseases

• Loss of myelin occurs when the process of myelin is destroyed.
• In the CNS, myelinated axons are the components of white matter, resulting in damage.
• This occurs as either acquired or inherited issues.
• Mulitple Sclerosis is an autoimmune result of the mylein which is destroyed.
• This can result in lesions and white matter damage.

Neurodegenerative Diseases

• Accumulation of protein and cell death result from the various diseases.
• Diseases affecting the cortex may cause cognitive issues.
• Diseases that affect the ganglia cause movement disorders.
• Diseases that have an effect on the cerebelum cause disorders for the body, such as balancing.
• Amyotrophic Lateral Sclerosis results in weakness, and difficulty breathing and swallowing due to issues in the spinal cord.
• Various proteins aggregates either because of mutations or defects in protein. clearance.