Cellular pathology of the central nervous system
Neurons
Acute injury (sometimes referred to as “red neurons”) is a result of acute hypoxia/ischemia or other insults that causes a spectrum of changes:
- Cell body shrinkage
- Pyknosis of nucleus
- Disappearance of nucleus
- Loss of Nissl substance
- Intensification of eosinophilla of the cytoplasm
Progressive disease processes (e.g. amyotrophic lateral sclerosis and Alzheimer disease) causing neuronal death is generally referred to as subacure and chronic injury. Histological changes include cell loss often of selectively involving functionally related neurons accompanied by reactive gliosis. Gliosis is often the best indicator of neuronal injury as cell loss is difficult to detect.
They process of axon regeneration (after injury) is termed the axonal reaction and is characterized by:
- Increased protein synthesis
- Axon sprouting accompanied by rounding of cell body
- Peripheral displacement of the nucleus
- Enlarged nucleolus
- Central chromatolysis (dispersion of Nissl substance to periphery of cell)
Subcellular alterations to organelles and the cytoskeleton can cause intracytoplasmic accumulations of lipofuscin, proteins, or carbohydrates and are often caused by genetic disorders (see Chapter 5: Genetic disorders, are manifestations of aging, or can be caused by viral infections: cowdry bodies associated with herpetic infection, negri bodies associates with rabies, or inclusions in either the nucleus or cytoplasm due to cytomegalovirus infection. Neurofibrillary tangels and Lewy bodies accumulate in Alzheimer and Parkinson, respectively. Other disorders such as Creutzfeldt-Jakob disease cause vacuolization of the perikaryon and neuronal processes of the neuropil.
Astrocytes
Gliosis—the most important histopathologic characteristic of CNS injury—is characterized by hypertrophy and hyperplasia of astrocytes, metabolic buffers of the brain and contributors to the blood-brain-barrier. Gliosis is often seen in hypoxic, hypoglycemic, and toxic insult injuries. Chronic hyperammonemia—as in Wilson disease, for example—can cause formation of Alzhemier type 2 astrocytes (unrelated to Alzheimer disease), which has many of the features of gliosis. Rosenthal fibers: thick, eosinophilic bodies containing heat-shock proteins—are often seen in regions of chronic gliosis and is characteristic of pilocytic astrocytoma (a glial tumor).
Microglia
Other glial cells
Cerebral edema, hydrocephalus, raised intracranial pressure, and herniation
Neural tube defects
Failed closure or reopening of the neural tube account for the majority of CNS malformations mostly commonly affecting the spinal cord.
- Spinal dysraphism or spina bifida: An asymptomatic bony defect (spina bifida oculta) with mild dermal anomalies or sever malformation—flattened or tangled disorganization—with associated overlying meningeal herniation
- Mylenomenigocele: Extrusions of the CNS tissue through a defect in the vertebral column, most commonly in the lumbosacral region causing motor-sensory deficits in lower extremities, incontinence, infections into the CNS from inefficiencies in the overlying skin. The much less common menigocele refers to only meningeal extrusion.
- Encephalocele: A diverticulum of CNS tissue in the cranium most often in the posterior fossa but can include extrusions through the cribiform plate, sometimes called nasal gliomas.
Failed closure of the anterior neuropore results in the anencephaly: absence of brain tissue and calvarium—occurring at approximately 28 days
Forebrain anomalies
The total number of neurons is regulated by the number of progenitor cells that move from symmetric to asymmetric division. If progenitor cells leave the proliferating pool too early or late the number of neurons will be too few or too many. Cells live the germinal matrix zone to become excitatory neurons or inhibitory interneurons via radial and tangential migration. Defects in migration lead to effect formation of gyri and sulci.
- Volume abnormalities: Megalencephaly and microenecphaly. The latter is much more common and has a variety of etiologies: chromosome abnormalities, fetal alcohol syndrome, HIV-1 infection in utero—but it is postulated that it is a result of an insufficient number of neurons leading to simplified gyral folding.
- Lissencephaly: A spectrum of fewer gyri: agyria, smooth surfaced type 1, and cobblestone surfaced type 2. Type 1 is associated with pathogenic variants in cytoskeletal motor proteins while type 2 is associates with in disruptions of the “stop signal” for migration.
- Polymicrogyria: Typically bilateral symmetric small, numerous, irregular cerebral convolutions leading to entrapment of meningeal tissues with what would be the cortical surface.
- Neuronal heterotopias are defined by collections of neurons in atypical locations that can be caused by a variety of pathogenic variant involved in neuronal migration; some of which are on the X chromosome. Heterotopias are associated with epilepsy.
- Holoprosencephaly: A spectrum of disorders characterized by failed formation of the cerebral hemispheres, which manifests as: cyclopia, arrhinencephaly or absence of cranial nerve 1, or single central incisor. It is also associated with trisomey 13. Its etiology causes defects in the sonic hedge hog signalling pathway of the notochord and related structures.
- Agenesis of cropus callosum: This can present in isolation or as part of a syndrome and is associated with inhibition of higher cognitive function.
Posterior fossa anomalies