8. The Nervous System

Question 1

Edema, Herniation, and Hydrocephalus

Answer 1

• Cerebral edema is the accumulation of excess fluid within the brain parenchyma. Hydrocephalus is defined as an increase in CSF volume within all or part of the ventricular system.
• Increases in brain volume (as a result of increased CSF volume, edema, hemorrhage or tumor) raise the pressure inside the fixed capacity of the skull.
• Increases in pressure can damage the brain by decreasing perfusion or by displacing tissue across dural partitions inside the skull or through openings in the skull (herniations).

Question 2

Central Nervous System Trauma

Answer 2

• Physical injury to the brain can occur when the inside of the skull comes into forceful contact with the brain.
• In blunt trauma, there may be brain injury both at the original point of contact (coup injury) and on the opposite side of the brain (contrecoup injury) owing to impacts with the skull.
• Rapid displacement of the head and brain can tear axons (diffuse axonal injury), often causing severe, irreversible neurologic deficits.
• Traumatic tearing of blood vessels, depending on the location, leads to epidural, subdural, or intraparenchymal hematoma as well as subarachnoid hemorrhage.

Question 3

Congenital Malformations and Perinatal Brain Injury

Answer 3

• Malformations of the brain can occur because of genetic factors of external insults.
• The developmental timing and position of the injury determine its pattern and characteristics.
• Various malformations stem from failure of neural tube closure, improper formation of neural structures, and altered neuronal migration.
• Perinatal brain injury mostly takes one of two forms: (1) hemorrhage, often in the region of the germinal matrix with the risk for extension into the ventricular system; and (2) ischemic infarcts, leading to periventricular leukomalacia.
• Certain infections may affect the brain during development with subsequent tissue destruction and neurologic consequences.

Question 4

Infections of the Nervous System

Answer 4

• Pathogens from viruses through parasites can infect the brain; in addition, prion disease is a protein-induced transmissible disease that is unique to the nervous system.
• Different pathogens use distinct routes to reach the brain, and they cause different patterns of disease.
• Bacterial infections may cause meningitis, cerebral abscesses, or a chronic meningoencephalitis.
• Viral infections can cause meningitis or meningoencephalitis.
• HIV can directly cause meningoencephalitis, or indirectly affect the brain by increasing the risk for opportunistic infections (toxoplasmosis, CMV) or CNS lymphoma.
• Prion diseases are transmitted by an altered form of a normal cellular protein. They can be sporadic, transmitted, or inherited.

Question 5

Primary Diseases of Myelin

Answer 5

• Because of the critical role of myelin in nerve conduction, diseases of myelin can lead to widespread and severe neurologic deficits.
• Multiple sclerosis, an autoimmune demyelinating disease, is the most common disorder of myelin, affecting young adults. It often pursues a relapsing-remitting course, with eventual progressive accumulation of neurologic deficits.
• Other, less common forms of immune-mediated demyelination often follow infections and are more acute illnesses.
• Leukodystrophies are genetic disorders in which myelin production or turnover is abnormal.

Question 6

Neurodegenerative Diseases

Answer 6

• Neurodegenerative diseases cause symptoms that dpend on the pattern of brain involvement. Cortical disease usually manifests as cognitive change, alterations in personality, and memory disturbances; basal ganglia disorders usually manifest as movement disorders.
• Many of the neurodegenerative diseases are associated with various protein aggregates, which serve as pathologic hallmarks. Familial forms of these diseases are associated with mutations in the genes encoding these proteins or controlling their metabolism. Some of these protein aggregates can show prion like properties, facilitating spread from one cell to the next.
• Among dementias, Alzheimer disease (with plaques of AB and tangles of tau) is the most common; other predominantly dementing disease include the various forms of FTLDs (both forms with tau-containing lesions and with other types of inclusions) and dementia with Lewy bodies (with a-synuclein containing lesions).
• Among the hypokinetic movement disorders, Parkinson disease is the most common, with a-synuclein containing inclusions.
• Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, with diverse genetic causes as well as sporadic forms.

Question 7

Tumors of the Central Nervous System

Answer 7

• Tumors of the CNS may rise from the cells of the coverings (meningiomas), the brain (gliomas, neuronal tumors, choroid plexus tumors), or other CNS cell populations (primary CNS lymphoma, germ cell tumors), or they may originate elsewhere in the body (metastases).
• Even low-grade or benign tumors can have poor clinical outcomes, depending on where they occur in the brain.
• Distinct types of tumors affect specific brain regions (e.g., cerebellum for medulloblastoma, an intraventricular location for central neurocytoma) and specific age populations (medullablastoma and pilocytic astrocytomas in pediatric age groups, and glioblastoma and lymphoma in older patients).
• Glial tumors are broadly classified into astrocytomas, oligodendrogliomas, and ependymomas. Increasing tumor malignancy is associated with more cytologic anaplasia, increased cell density, necrosis and mitotic activity.
• Metastatic spread of brain tumors to other regions of the body is rare, but the brain is not comparably protected against the spread of distant tumors. Carcinomas are the dominant type of systemic tumors that metastasize to the nervous system.