Central chromatolysis (axonal reaction)

• A process in when axons are severely injured and cell bodies swell and lose some of their components.

  • This process is reversible

    • Ischemic cell change is **__NOT __**reversible

Wallerian degeneration

• Degeneration of the axon pistol to the point of separation

In the PNS, regeneration of the nerve is possible if the cell body survives

• Functionally significant regeneration of axons does not occur in the CNS.

Neurofibrillary degeneration

• Characterized by the formation of clumps in neurofibrils in the cytoplasm of CNS neurons.

  • Most common form of degeneration associated with dementia (Alzheimer's disease)

Senile plaques

• A related pathogenic change

  • Characterized by fibrous protein deposits, amyloid, in cell bodies and degenerated nerve processes.

Inclusion bodies

• Abnormal, discrete deposits in nerve cells

  • Presence may identify specific diseases such as Parkinson’s, Pick’s, and certain viral infections

Storage cells

• Abnormal accumulations of metabolic products in nerve cells

  • Aka “balloon cells”

Injury to a CNS axon usually does not result in death of postsynaptic neurons, but activities of postsynaptic neurons may be altered by diaschisis (a process in which the neurons function abnormally because influences necessary to their normal function have been removed by damage to neurons to which they are connected).

• May explain abnormalities in neuronal function at sites distant from a lesion in the CNS.

Positron emission tomography (PET)

• Demonstrated that neuronal cell death in one region of the brain can lead to changes in metabolic functions of adjacent and even distant regions to which the damaged area has important anatomic connections.

  • Highlight the importance of interrelationships among groups of neurons in CNS.

Demyelinating disease

• Meylin is attacked by some exogenous agent, broken down, and absorbed.

  • Most common is MS but also occurs in other CNS and PNS diseases (such as Guillain-Barre syndrome).

  • ***Leukodystrophies ***are diseases in which myelin is abnormally formed in response to inborn errors in metabolism which leads to the eventual breakdown of myelin.

Astrocytes react to many CNS injuries by forming scars in injured neural tissue.

• Referred to as gliosis, astrocytosis, astrogliosis

  • May also react more specifically to metabolic diseases (hepatic - liver failure) or form inclusion bodies in cell nuclei in response to certain viral infections.

The localization of neurologic disease can be broadly characterized as:

• Focal

  • Involving a single circumscribed area or contiguous group of structures

    • Frontal lobe

• Multifocal

  • Involving more than one area or more than one group of contiguous structures

    • Cerebellar and cerebral hemisphere plaques associated with MS

• Diffuse

  • Involving roughly symmetric portions of the nervous system bilaterally

    • Generalized cerebral atrophy associated with dementia

The development of symptoms can be:

• Acute

  • Within minutes

• Subacute

  • Within days

• Chronic

  • Within months

The evolution or course of the disease after symptoms have developed can be:

• Transient

  • When symptoms resolve completely after onset.

• Improving

  • When severity is reduced but symptoms are not resolved.

• Progressive

  • When symptoms continue to progress or new symptoms appear.

• Exacerbating-remitting

  • When symptoms develop, then resolve or improve, then recur or worsen, and so on.

• Stationary (Chronic)

  • When symptoms remain unchanged for an extended time

Degenerative diseases

• Characterized by gradual decline in neurologic function of unknown cause.

  • Many are probably genetically determined biochemical disorders that share basic mechanisms that lead to neuronal death.

  • Most often chronic, progressive, and diffuse, but sometimes begin with focal manifestations.

Inflammatory Diseases

• Characterized by an inflammatory response to microorganisms, toxic chemicals, or immunologic reactions.

• Pathologic Hallmark is an outpouring of white blood cells

  • Development of clinical signs and symptoms is usually subacute.

  • Include but aren’t limited to infectious processes

• Many are progressive and diffusely located in the leptomeninges and CSF (as in meningitis) or in the brain parenchyma (as in encephalitis).

• Inflammation in the PNS may occur in single nerves (mononeuritis) or in multiple nerves (polyneuritis).

• Inflammatory diseases in the CNS are focal and may be abscess formation

  • a process in which astrocytes proliferate to form a wall of flail fibers that limits spread of infection

    • Eventually leaving a cavity that reflects loss of the enclosed brain tissue.

Toxic Metabolic diseases

• Vitamin deficiencies, thyroid hormone deficiency, genetic biochemical disorders, complications of kidney and liver disease, hypoxia, hypoglycemia, hyponatremia, and drug toxicity.

  • Effects are usually diffuse and development can be acute, subacute, or chronic.

Neoplastic Diseases

• Any cell type in the nervous system can become neoplastic but because neurons in the adult nervous system do not normally undergo cell division, neuronal neoplasms are rare.

• Astrocytes are very reactive and astrocytomas are the most common primary CNS tumor.

• Tumors are often named after the cell types from which they arise.

• PNS tumors rarely metastasize (spread) outside the CNS, but systemic cancer can spread to the CNS.

• Tumors usually create focal signs and symptoms and are chronic or progressive in their course

• Not all progressive mass lesions represent a neoplasm.

Trauma

• Usually has an identifiable precipitating event (gunshot, fall, car accident)

• Onset is almost always acute with maximum damage around the time of onset

• PNS traumatic injuries can be focal or multifocal.

• CNS traumatic injuries are often diffuse initially, as in concussion (an immediate and transient loss of consciousness or other neurologic function after head injury).

• Residual focal signs and symptoms tend to reflect areas of severe anatomic damage, as can occur with contusions, lacerations, and hematomas.

• An exception to general rule of acute onset of signs and symptoms from trauma can occur in subdural hematoma

  • The bleeding in this case is under low pressure because it occurs in veins crossing from the brain to the dural sinuses where blood is then drained from the brain.

• Traumatic Brain Injury (TBI) can be subdivided into penetrating and closed head injury.

  • Penetrating Head Injury (bullets or shrapnel)

    • Can produce relatively focal neurologic abnormalities.

  • Closed Head Injury (falls, sports injuries, car accidents)

    • Cognitive deficits are the most common and persistent neurological deficit associated with CHI.

      • Up to 60% of people with CHI in acute rehabilitation settings may be dysarthric.

    • Injuries from CHI can create focal lesions, diffuse axonal injury, and superimposed hypoxia or ischemia and microvascular damage.

      • Focal contusions (superficial injuries characterized by leptomeningeal hemorrhage and variable degrees of edema) often occur at the site of impact and result in focal neurologic deficits; they are known as coup injuries.

      • Contrecoup lesion: if the injury is associated with acceleration, the motion of the brain may also cause trauma at sites opposite the point of impact.

    • Most common sites of these focal injuries: orbitofrontal region and the anterior temporal lobes

      • Locations where the brain abuts on edges of the skull and are subject to trauma when the head rapidly decelerates.

        • Causes rupture of veins in the area of trauma, although hemorrhage in CHI can be extradural, subdural, subarachnoid, or intracerebral.

    • Diffuse axonal injury is a consistent, biologically complex contributor to neurologic deficits in mild-to-severe CHI

    • Occurs more frequently when trauma is associated with rotational forces and reflects a shearing of axons, potentially in numerous brain areas

      • Centrum semiovale, corpus callosum, and brainstem

    • Trauma creates a physiologic response in affected axons that can lead to their swelling and eventual Wallerian Degeneration, effectively disrupting functions of the networks in which they play a role.

    • Other physiological responses that can occur include: hypoxia and ischemia in response to stretch and strain on blood vessels, subtle problems with metabolic and vascular regulatory processes, and neuroinflammation.

      • TBI from blast injuries is more complicated physiologically than TBI associated with non blast causes.

        • The high-force pressure wave from an explosion can injure the brain internally and can be combined with penetrating injuries such as shrapnel.

    • Many of these anatomic and physiologic sequelae and their effects on cognitive and sensorimotor functions can be negatively influenced by comorbid factors such as age, previous history of psychiatric disorder, substance abuse, lower socioeconomic status, and possibly genetic variations.

Vascular Diseases

• The most common cause of neurologic deficits and possibly MSDs

• The most common cerebrovascular disease is stroke (infarct or cerebrovascular accident [CVA])

  • Where neurons are deprived of oxygen and glucose because of an interruption in blood supply (inchemia)

    • Neurons don’t function within seconds of ischemic event

    • Pathologic changes occur in minutes

• Stroke

  • Almost always sudden in onset

  • Usually focal

  • Embolic stroke

    • Tend to develop suddenly and without warning

    • Emboli usually comes from the heart

• Edema

  • Cerebral edema is common in stroke because ischemia affects the blood-brain barrier, neuronal, and glial cell membranes

  • Fluid may collect in the extracellular space and cause significant increase in intracranial pressure

  • May be cytotoxic

    • Intracellular accumulation of water occurs

  • Vasogenic and cytotoxic edema often occur in response to a stroke

• Ischemic

  • Common cause: embolism

    • Fragments of material travels through a blood vessel to a point of arterial narrowing sufficient to block its passage

  • Account for about 80% of strokes

• Thrombosis strokes

  • Narrowing and occlusion of an artery at a fixed point

  • Can cause ischemia

  • Reflects a build up of plaque made up of liquids and fibrous material on the inner wall of a vessel

  • Usually occurs in the internal carotid, vertebral, or basilar arteries

  • Sometimes preceded by transient ischemic attacks (TIAs)

    • Neurological symptoms that last for seconds to minutes and are a warning sign of cerebrovascular disease and impeding a stroke

    • Most common symptoms:

      • Motor speech

      • Language deficits

  • Not all are associated with atherosclerosis

• Aneurysms

  • Balloon-like malformations in weakened areas of arterial walls

  • Most commonly found in:

    • Internal carotid

    • Anterior or middle cerebral artery

• Cerebral hemorrhage

  • A vessel ruptures into the brain, with an accumulation of blood in neural tissue

  • Associated with:

    • High blood pressure

    • Chronic hypertension

  • Symptoms appear abruptly and are

  • Common sites of intracerebral hemorrhages

    • Thalamus

    • Basal ganglia

    • Brainstem

    • Cerebellum

• Subarachnoid hemorrhage (SAH)

  • Most common extracerebral hemorrhage

  • When blood vessels rupture on the surface on the brain and blood spreads over its surface and throughout the subarachnoid space

  • Onset: abrupt

  • Causes:

    • Most common: ruptured aneurysms

    • Could also be from arteriovenous malformation (AVM)

      • Collection of abnormally formed veins and arteries

      • Can become enlarged by expansion of weak vessel walls

      • Create neurologic symptoms through mass effects

    • Could occur if weakened walls rupture

    • Closed head injury (CHI)

      • Dural blood vessels are torn apart