Chapter 22 The Central Nervous System

REACTION OF THE CENTRAL NERVOUS SYSTEM TO INJURY

2 List the most important pathologic reactions of neurons

Acute injury: This is most commonly caused by hypoxia/ischemia but also under the influence of toxic or infectious agents that can kill neurons. Affected neurons have pyknotic nuclei and an acidophilic cytoplasm, which stains intensely red with eosin (“red is dead”) in standard hematoxylin and eosin (H&E) slides.

Axonal reaction: It occurs following transection or other severe injury of the axon and is characterized by histologic and ultrastructural changes in the cytoplasms of the neuron (perikaryon). Following axonal injury, the perikaryon swells. Ultrastructurally, the ribosomes of rough endoplasmic reticulum (RER) are lost. This degranulation of the RER, which in the neurons is called Nissl substance, is visible by light microscopy as a loss of basophilia and is called chromatolysis.

Formation of neuronal inclusions: Neuronal inclusions can be intracytoplasmic or intranuclear. Typical examples include lipofuscin (i.e., the cytoplasmic brown “wear and tear” pigment of aging) and viral inclusions (cytoplasmic inclusions, e.g., the Negri bodies in rabies; nuclear inclusions such as those seen in herpes encephalitis and known as Cowdry type A bodies; or nuclear and cytoplasmic inclusions such as in cytomegalovirus infection).

Aggregation of abnormal proteins: Cytoplasmic bodies are found in neurons in several neurodegenerative diseases, such as the formation of neurofibrillary tangles in Alzheimer disease or the formation of cytoplasmic Lewy bodies made out of α-synuclein in Parkinson disease.

Neuronophagia: Phagocytosis of damaged neurons by microglial and inflammatory cells is a common reaction to CNS injury in various infectious or toxic diseases.

4 How do microglial cells respond to CNS injury?

Microglia cells are bone-marrow-derived macrophages that accumulate at the site of CNS injury, forming glial nodules. Activated microglial cells show nuclear elongation resulting in rod cells. Microglia cells take part in phagocytosis of dying neurons, a process known as neuronophagia.

5 What are the common forms of cerebral edema?

Three forms of cerebral edema are recognized: vasogenic, cytotoxic, and interstitial.

Vasogenic edema: It is characterized by the accumulation of fluid in between the neurons and glial cells and most prominently in the Virchow–Robin spaces around the blood vessels. It develops as a consequence of blood–brain barrier dysfunction. Fluid escapes from the vascular space into the interstitial space of the parenchyma across the cytoplasm of vascular endothelial cells or between these cells through the disrupted tight junctions. It may be localized (e.g., around a tumor or an abscess) or generalized (e.g., in encephalitis or following head trauma).

Cytotoxic edema: In this form of edema, the fluid accumulates inside the cells. It is most frequently caused by ischemia, hypoxia, or both, which lead to hydropic swelling of neurons and glial cells.

Interstitial edema: It is the result of increased intracerebral influx of CSF through the ependymal lining. Fluid from the ventricles enters into the periventricular white matter, typically under conditions associated with an increased intraventricular CSF pressure. This form of edema is typically a complication of hydrocephalus.

7 Describe various forms of intracranial cerebral or cerebellar herniations

Herniations (Fig. 22-1) occur as a result of increased intracranial volume. Most often, they accompany space-occupying lesions, such as tumors, hematomas, or abscesses, but they may also be caused by trauma. The displacement of parts of the brain is morphologically most evident at three herniation sites:

Cingulate herniation (subfalcine herniation): It results from a unilateral hemispheric mass lesion (e.g., abscess, hematoma, and tumor) that expands the volume of one hemisphere, dislocates the midline structures (midline shift), and forces the ipsilateral cingulate gyrus to be compressed (“herniate”) underneath the falx cerebri. Focal necrosis and hemorrhage may develop in the herniated tissue together with distant reduction of blood flow (i.e., compression of the anterior cerebral artery).

Transtentorial herniation (uncinate herniation): It is caused by the expansion of one or both supratentorial tissue compartments (cerebral hemispheres). The uncus gyri hippocampi is displaced on one or both sides and is herniated underneath the free edge of the rigid cerebellar tentorium. Simultaneously, the ipsilateral third cranial nerve is compressed between the tentorium and the expanding temporal lobe, as indicated by the dilatation of the ipsilateral pupil plus abnormal eye movements on the same side.

Tonsillar herniation: It may develop unilaterally or bilaterally and is a life-threatening condition because the herniated cerebellar tonsils that are forced into the foramen magnum compress the vital respiratory and cardiac centers within the medulla oblongata. Compression of vital centers may cause cardiac or respiratory paralysis (or both).

Figure 22-1 Cerebral herniations.

(From Stevens A, Lowe J: Pathology. London, Mosby, 1995. Reproduced with permission, p. 399.)

DEVELOPMENTAL DISORDERS

8 Define dysraphic malformations and list the most common forms of this malformation

Dysraphic malformations result from a failure of the dorsal closure of the fetal neural tube. Two main forms of dysraphism are recognized: cranial and spinal. Both occur in several subtypes.

Cranial dysraphism: It is associated with incomplete formation of the skull and occurs most often as anencephaly or encephalocele. This severe cerebral malformation is usually incompatible with life.

Spinal dysraphism: This group of developmental disorders includes spina bifida occulta, meningocele, meningomyelocele, and rachischisis, all of which are characterized by variably severe defective closure (most commonly) of the lumbosacral segment of the neural tube, vertebral arches, and, in the most severe cases, the skin. Severe forms of spinal dysraphism are not compatible with life. Spina bifida occulta, however, is not life threatening and is typically accompanied only by neurologic defects affecting the lower extremities.

PHYSICAL INJURY

10 What are the main forms of spinal cord or brain injury caused by physical forces?

Skull fractures are often accompanied by parenchymal injuries, which include:

Contusions (“bruising”): This type of injury results from rapid deceleration or acceleration of the skull and the brain. Typically it involves a coup lesion at the site of the impact of force or a contrecoup contusion, diametrically opposite to it.

Lacerations (tearing of tissue): It is a severe form of brain injury typically seen in vehicular accidents. It is associated with bleeding and high mortality.

Diffuse axonal injury: It is usually found in the parasagittal or deep centroaxial white matter. Such injury results from the action of shearing forces in laminar planes within the brain and is frequently accompanied by focal hemorrhages.

Tearing of cerebral blood vessels: This traumatic vascular injury is accompanied by bleeding.

Penetrating wounds: These are most often caused by bullets.

Key Points: Physical Injury

1. Physical injury may directly damage the brain and the spinal cord, or it may cause hemorrhages, which cause secondary brain lesions.

2. Hemorrhages into various compartments of the intracranial space produce distinct clinical syndromes, but all of them may be lethal.

11 Describe the most common spinal cord injuries

Concussions, contusions, lacerations, and penetrating injuries are similar to those elsewhere within the CNS. Unique to the spinal cord are the hyperextension and hyperflexion injuries.

Hyperextension injury: It typically occurs in the cervical spine and is caused by sudden posterior displacement of the head that causes rupture of the anterior spinal ligament. The so-called posterior angulation of the cervical vertebrae is accompanied by contusion of the posterior segment of the cervical spinal cord.

Hyperflexion injury: It also affects the cervical spine and results from trauma that leads to a compression of one of the cervical vertebrae. Such a “teardrop” fracture of the vertebral body is usually caused by an impact force that rapidly drives the head down and forward. This is accompanied by anterior angulation and consecutive anterior contusion of the cervical spinal cord.

13 What is epidural hematoma ?

Epidural hemorrhage results from bone fractures at the base of the skull that tear the middle meningeal artery. Arterial bleeding leads to the formation of a hematoma in the virtual space between the inner aspect of the cranial bones and the dura mater. Hematoma that forms under arterial pressure grows progressively, and without proper surgical intervention, it is invariably fatal within several hours after injury.

VASCULAR DISORDERS

15 List the most common aneurysms found in the CNS

An aneurysm is a circumscribed, segmental dilatation of an artery. The most important forms of intracranial aneurysms are:

Berry aneurysms: These small saccular aneurysms are typically found in and around the circle of Willis at the base of the brain. They develop at the site of arterial branching corresponding to the congenital weakest part of the vessels. The rupture of these aneurysms leads to a usually fatal subarachnoid and/or intraparenchymal/intraventricular hemorrhage.

Atherosclerotic aneurysms: These aneurysms may involve the extraparenchymal or intracerebral arteries. Most often, they are asymptomatic and rarely rupture.

Hypertensive microaneurysms: Long-standing hypertension leads to deposition of lipid–hyaline substances within the wall of small branches of penetrating arteries and arterioles. These deposits weaken the vessel wall and cause microscopic Charcot–Bouchard aneurysms.

Key Points: Vascular Disorders

1. Stroke can be caused by intracerebral hemorrhage or infarction.

2. Ischemia of the brain may cause only transient functional changes or a variety of lesions, such as watershed infarct and laminar necrosis.

16 What are cerebral arteriovenous malformations?

Arteriovenous malformations (AVMs) result from defective formation of capillaries in a normal part of the brain. The arterial blood thus enters directly into the veins, usually by way of arteriovenous anastomoses that form at the defective site. Typical AVMs consist of tortuous arteries and veins that form cortical–subcortical networks of “wormlike” arteriovenous shunts embedded in hemosiderin–laden glial tissue. AVMs have a high blood flow, often pulsate, and may be a source of mixed parenchymal/subarachnoidal bleeding and seizures.

17 List the most important causes of nontraumatic intracerebral hemorrhage (i.e., hemorrhagic strokes)

Hypertension: Chronic, severe (usually uncontrolled), systemic hypertension is the most common cause of hemorrhagic stroke. Hypertension accelerates arteriosclerosis of the larger arteries and also causes lipohyalinosis of the smaller branches promoting the development of rupture-prone Charcot–Bouchard aneurysms. Hypertensive hemorrhages occur most often within the basal ganglia and less commonly in the cerebellum or the medulla oblongata.

Coagulation abnormalities: Most often, this kind of hemorrhage occurs in terminal stages of leukemia and severe thrombocytopenia.

Rupture of berry aneurysms: Because the blood exits the ruptured arteries under pressure, it may penetrate into the cerebral parenchyma and even into the ventricles. Thus the blood may be found not only in the subarachnoid space but also inside the brain (mixed bleeding: subarachnoidal plus parenchymal/intraventricular).

18 What are the most common sites of hypertensive cerebral hemorrhages?

Basal ganglia and thalamus (65%)

Pons (15%)

Cerebellum (10%)

20 What are the most important causes of occlusion of cerebral arteries?

Thrombi: Most thrombi form over ruptured atheromas. They account for 80% cerebral infarcts.

Thromboemboli: Most of these stem from the heart chambers or valves and the large arteries.

INFECTIONS

23 List the most common causes of acute bacterial meningitis

The infection can be caused by a variety of microorganisms. Streptococcus pneumoniae has become the most common cause because immunization has eliminated many other causes such as Hemophilus influenzae. In neonates it is most commonly caused by Escherichia coli and group B streptococci. Among children and young adults, an important cause is Neisseria meningitidis (meningococcus), which may cause miniepidemics among army recruits or in student camps. Gram-negative bacteria (E. coli, Klebsiella, and Enterobacter) cause meningitis in immunosuppressed people following brain trauma or brain surgery.

26 Describe the pathologic findings in chronic meningitis

The pathologic findings in various forms of chronic meningitis vary depending on the causative pathogen. The infection is usually more circumscribed than in acute meningitis and may be localized to parts of the brain. For example, tuberculous meningitis typically involves the basal cisterns and the lateral sulci that contain gelatinous whitish gray material. Histologically, these lesions contain caseating granulomas. In secondary and tertiary syphilis, the meninges show focal irregular thickening. These changes are most prominent around the spinal cord but may be seen over the convexity of the brain or over the cerebellum. Histologically, thickened meninges contain infiltrates of lymphocytes and plasma cells, typically arranged around the meningeal blood vessels. Tertiary syphilis may also present in the form of a granulomatous inflammation (gumma of syphilis).

27 List the most important causes of viral meningitis

Viral meningitis (also known as aseptic meningitis) may occur as part of a systemic viral disease (e.g., varicella, mumps, and measles), or it may be limited to the CNS. The latter may be sporadic (e.g., herpes virus infection) or epidemic (e.g., arboviruses transmitted by arthropods such as eastern or western equine encephalitis), and is often associated with encephalitis (i.e, meningoencephalitis).

28 What is tabes dorsalis?

Tabes dorsalis (Fig. 22-2) is a manifestation of tertiary syphilis involving the lumbar spinal cord. Syphilitic meningitis leads to fibrosis, compressing the posterior nerve roots. In normal circumstances, these afferent nerves, originating from the spinal ganglia, form the posterior columns in the spinal cord, and transmit proprioceptive and sensory impulses. Wallerian degeneration that results from the injury of axons entering the spinal cord results in posterior columns. Clinically, these patients experience loss of vibration and proprioception, which affects their gait. Joint degeneration resulting in deformities (Charcot joints) is commonly found.