Chapter 21: Nervous System

Cortex and subcortical gray matter

• composed of numerous neurons and support cells. • axons emanating from the nerve cell bodies extend into the white matter, where they become myelinated. • Myelinated axons extend from the white matter into other parts of the brain and into the spinal cord.

Prions

• minute infectious particles composed only of proteins that are smaller than viruses • survive only in nerve cells and are therefore selectively harmful to the CNS. • cause spongiform degeneration of the brain that is typical of such diseases as kuru and Creutzfeldt-Jakob disease

Tonsillar herniation

involves the cerebellar tonsils protruding into the foramen magnum.

Subfalcine herniation

involves the cingulate gyrus protruding beneath the falx cerebri.

Transtentorial (uncinate) herniation

involves the uncus protruding below the tentorium cerebelli.

Herpesvirus

• most common viral cause of localized encephalitis in the United States

Rabies

• neurotropic viruses that infects only nerve cells.

Neck and Spinal Cord Injuries

• "Backlash injury" of the neck is the most common • injuries of the cervical spine have traditionally been classified as either hyperextension or hyperflexion injuries • in hyperextension injury, an impact on the forehead causes hyperextension and rupture of the anterior spinal ligaments, with subsequent compression of the posterior side of the spinal cord • in hyperflexion injury, the impact on the occiput causes extensive anterior flexion of the spinal cord and compression of the anterior portion of the spinal cord. • Both hyperextension and hyperflexion injuries may cause complete transection of the spinal cord, resulting in a loss of both motor and sensory functions below the site of injury. • Typically, the injured person experiences flaccid paralysis accompanied by a loss of sensation below the site of injury. • Urination and defecation reflexes are also lost. • With time, the reflex functions return and the paraplegia or quadriplegia becomes spastic. • The reflexes governing the bladder and bowel functions may also be partially restored. (Damjanov, 2016, p. 478)

Cerebral Infarct

• An infarct or ischemic necrosis of a distinct anatomic part of the brain caused by CVD clinically presents as a stroke • most often caused by thrombotic occlusion of an atherosclerotic artery • thromboemboli originating in the heart chambers (e.g., after a myocardial infarction) or on the cardiac valves (e.g., resulting from endocarditis) are the second most common causes • pathologic changes in the brain vary depending on the time that has elapsed since the onset of occlusion.

Affect of Other Diseases on CNS

• CNS is affected by many multisystemic diseases, especially those classified as circulatory, metabolic, or infectious. • atherosclerosis of the coronary arteries and aorta is often accompanied by cerebrovascular accidents (CVAs) • End-stage kidney disease (uremia) or liver disease (cirrhosis) may be accompanied by metabolic disturbances that typically cause numerous neurologic symptoms. • Systemic infections caused by various bacteria or viruses may spread to the brain, usually by a hematogenous route.

herniations of the brain

• Death caused by increased intracranial pressure usually results from the compression of vital centers in the brainstem. • Most often, the centers of the medulla oblongata are compressed by the edematous tonsils of the cerebellum, which herniates through the foramen magnum

Glial cells

• support the neurons • facultative and mitotic (labile) cells • capable of dividing when properly stimulated. • retain a capacity for multiplication and are capable of multiplying in response to certain forms of injury.

Foramina of Luschka and Magendie

• From the fourth ventricle, the CSF may enter the central canal of the spinal cord or exit through the lateral openings (foramina of Luschka) and a median opening (foramen of Magendie) into the subarachnoid space.

arachnoid granulations of the meninges

• From the subarachnoid space, the CSF is resorbed through the arachnoid granulations of the meninges into the venous system.

uncal or transtentorial herniation

• Herniation of the medial portion of the cerebral hemisphere beneath the tentorium cerebelli may compress the pons and can also cause death

laminar necrosis

• Hypoperfusion also leads to laminar necrosis of the deeper zones of the gray matter • these zones receive blood from the short penetrator arteries entering the cortex from the surface → because of hypotension, the blood entering the cortex does not reach the deep cortex, and necrosis ensues. If heart function is restored, patients recover with only minor neurologic deficits • nevertheless, these minor CVAs have a cumulative effect and ultimately cause mental deterioration. (Damjanov, 2016, p. 475)

encephalomalacia ("softening of the brain")

• Ischemic brain liquefies, and the ischemic area undergoes necrosis, transforming into a puttylike mush • focus may remain pale (pale or bland infarct), or it may be perfused with blood from the collateral circulation and transform into a hemorrhagic infarct. • White matter infarcts usually remain pale, whereas those in the gray matter tend to transform into red infarcts • red infarcts are common after cerebral embolization with arterial thromboemboli because such infarcts are more readily perfused by arterial blood from adjacent, unoccluded blood vessels. • the brain tissue surrounding the infarcts, regardless of their color, is edematous. • During this phase of maximal cerebral swelling, patients experience the most profound neurologic deficits and are at the greatest risk of dying → within a few days after infarction, the cerebral edema subsides, and the condition of patients surviving this critical period improves in most instances. • The margins of the viable tissue surrounding the infarct become vascularized → the necrotic material is removed from the infarct by scavenger cells that invade the area from the newly formed blood vessels. • Ultimately the infarct transforms into a fluid-filled cavity (pseudocyst) • brain infarcts cannot heal, and the neurologic deficits caused by them are permanent.

Laceration of the brain

• Laceration of the brain is typically caused by open trauma that disrupts the integrity of the brain • gunshot wounds also produce laceration of the brain tissue → such wounds have high mortality • death is related to acute expansion of the intracranial volume and the consequent compression of the vital centers in the brainstem • patients who survive gunshot wounds of the brain usually have major neurologic deficits, and some of them may develop epilepsy (seizures). (Damjanov, 2016, p. 478)

Inborn Errors of Metabolism

• Metabolic injury of the brain is a common feature of many inborn errors of metabolism. • Diseases involving the enzymes essential for maintenance of myelin and cell membranes of neurons are accompanied by extensive lesions of the CNS

Neurons

• Neurons: nondividing, postmitotic, permanent cells • brain contains billions of neurons, all of which are formed during prenatal, intrauterine life. • long-lived cells → every hour you lose thousands of neurons to programmed natural death. • Lost neurons cannot be replaced because the remaining neurons cannot divide and the brain does not contain neuronal reserve cells → every loss of brain substance results in permanent defects.

2014 Stroke Facts

• On average, one American dies from stroke every 4 minutes. • Every year, more than 800 000 people have a stroke. • About 600 000 of these are first (i.e., new) strokes. • The others, nearly one of four, are in people who have had a previous stroke.

Neurotropic viruses

• viruses that exclusively infect neural tissue • known for their geographic provenance (e.g., St. Louis encephalitis) • transmitted by insects, such as mosquitoes and ticks. • often cause seasonal epidemics.

bacterial meningitis

• Streptococcus pneumoniae accounts for most cases of bacterial meningitis in adults • Group B streptococci, which often colonizes the female genital tract, can infect babies during birth and is the most important cause of bacterial meningitis in neonates • in neonates, meningitis also can be caused by Escherichia coli and Listeria monocytogenes • most important bacterial pathogens in older infants, children, and adolescents are Neisseria meningitidis (meningococcus) and S. pneumoniae.

CNS Development

• The CNS develops from the neural plate, which folds and ultimately closes into a neural tube extending along the dorsal side of the body axis • As the neural tube forms, it becomes internalized and is protected by the overlying skin. • The mesenchyme between the neural tube and the skin is induced to form bone, which gives rise to the skull and the vertebral bodies, which finally encase the brain and the spinal cord.

West Nile virus

• a mosquito bite-related viral infection that has become quite common in the US • associated with encephalitis in about 10% to 20% of cases • in elderly persons, or in those otherwise sick and debilitated, this infection may be lethal.

blood-brain barrier

• an anatomic and functional barrier known as the blood-brain barrier • acts like a filter, allowing the passage of some substances from the blood into the CSF while preventing the passage of others • For example, bilirubin does not enter the CNS compartment, even in the most severe forms of jaundice. • Glucose concentration in the CSF is 50 to 75 mg/dL and in general should be less than 66% of the blood concentration. • The protein concentration of normal CSF does not exceed 45 mg/dL, which is just a fraction of the concentration of protein in serum, approximately 7 g/dL.

Gliosis

• an increased number of glial cells • typical sign of brain injury • found around tumors, brain infarcts, and foci of intracerebral hemorrhages

External surface of the brain

• arranged into gyri, separated by invaginations called the sulci • On cross section, the brain forming the gyri is seen to be composed predominantly of gray matter, also known as cortex. • brain tissue beneath the cortex appears white (white matter) • deep parts of the brain also contain gray areas, which form the basal ganglia, thalamus, and hypothalamus.

watershed infarcts

• cardiac failure or any other form of vascular collapse results in widespread infarcts • such hypoperfusion infarcts are typically located in the parasagittal cortex, in the areas representing the marginal zones of arterial supply by the branches of the carotid artery on one side and the basilar artery on the other → systemic hypotension lowers the perfusion from both sides, and the area in the border zone becomes hypoxic → results in watershed infarcts.

Multiple sclerosis (MS) Etiology

• cause of MS is unknown. • Epidemiologic data indicate that MS occurs more often in whites of Western and Northern European origin who live in temperate climate zones above the 40th parallel than in people living in the tropics. • However, if persons at risk live for the first 15 years of life in a moderate climate and move to the tropics, they have the same high risk that they would have in their original climate. • Genetic studies have shown that MS affects certain families more often than others → the first-degree relatives of an affected person have a 15 times higher risk of developing the disease than the general population living under the same conditions. • If one monozygotic twin develops symptoms, the second twin will also become ill in 25% of cases. • Genetic linkage studies have disclosed a high prevalence of certain human major histocompatibility antigens among the affected individuals, further supporting the theory of genetic predisposition.

Japanese B encephalitis

• caused by an arthropod-borne virus • most common neurotropic virus associated with epidemic forms of encephalitis

Increased intracranial pressure

• caused by cerebral edema • may lead to loss of consciousness, progressing to coma and death. • Brain edema may be caused by numerous brain lesions, such as tumors, intracranial hemorrhage, inflammation, and numerous metabolic or circulatory disturbances, such as shock. • increased intracranial pressure is a life-threatening condition with symptoms that depend on the pace at which it develops • A sudden, explosive increase in intracranial pressure, such as that caused by a bullet wound to the head, will cause death instantaneously • by contrast, a rapid but gradual increase of intracranial pressure will present as a severe headache that is usually accompanied by vomiting, blurry vision, and loss of consciousness → such patients lapse into coma and usually die of apnea (absence of breathing) as a result of the inhibition of the medullary vital centers.

dysraphic disorders

• caused by incomplete fusion of the neural tube and defective formation of meninges, calvaria, or vertebras • occur in several forms

Brain contusion (bruise)

• characterized by a disruption of cerebral or meningeal blood vessels by severe blunt trauma • lesions are hemorrhagic and are typically located at the site of impact (coup lesion) and its diametrically opposite pole (countercoup lesion) • coup lesion is caused by direct force, whereas a countercoup lesion is a result of the deceleration of the moving brain caused by the skull bones that serve as shock absorbers • rotation of the head on impact causes even more damage • contusions of the brain are serious injuries associated with considerable mortality. • Survivors may have severe neurologic deficits, some of which may be permanent. (Damjanov, 2016, pp. 477-478)

Milder dysraphic malformations

• characterized by a lack of fusion of the posterior bone coverings • meningocele → meninges protrude through the bony defect • myelomeningocele → the protrusion contains the meninges AND a portion of the spinal cord

spina bifida

• characterized by an absence of vertebral arches, resulting in exposure of the meninges or the spinal cord to the outer world • may be evident at birth as a deep defect on the lower back, or it may be covered with skin and be inapparent (spina bifida occulta)

Neurodegenerative diseases

• characterized by neuronal degeneration and loss of neurons • etiology and pathogenesis of these neurodegenerative diseases are unknown

Multiple sclerosis (MS) Clinical Features

• chronic disease characterized by episodes of exacerbation and remission of neurologic symptoms. • Symptoms include both sensory and motor abnormalities. • Among the sensory defects, the most common is loss of sensation of touch, accompanied by tingling. • Blurred vision is a common early symptom. • Motor symptoms include muscle weakness, unsteady gait, incoordination of movements, and sphincter abnormalities such as urinary incontinence. • MRI useful → brain lesion is evident in 80% of patients. • Oligoclonal IgG bands are typically found in the CSF, and although this abnormality is not pathognomonic of MS, it strongly supports the diagnosis. • MS has an unpredictable course → most patients become physically incapacitated over a period of 20 to 30 years. • Patients who develop MS after the age of 40 years and those with marked motor disability early in the course of disease have a poor prognosis

Intracranial Hemorrhages

• classified into four groups according to their location • epidural, subdural, subarachnoid, and intracerebral

Intracerebral Hemorrhage

• common complication of head trauma • among the nontraumatic forms of intracerebral hemorrhages, the most important are various forms of stroke. • intracerebral hemorrhage is also common in leukemia and other hematologic diseases associated with abnormal coagulation (Damjanov, 2016, p. 475)

spinal cord

• consists of gray matter and white matter • in contrast to the brain, the gray matter of the spinal cord is located internal to the white matter, around the central canal • the gray matter has a butterfly-like shape on cross section, with anterior and posterior horns that consist of neurons and unmyelinated nerve fibers • neurons of the anterior horn give rise to peripheral nerves, which extend to the muscles and carry motor impulses • the white matter of the spinal cord consists of myelinated nerve fibers representing the descending motor tracts or ascending sensory tracts

peripheral nervous system

• consists of nerves emanating from the CNS and the autonomic nervous system • Each spinal nerve has an anterior root and a posterior root • ventral root consists of the axons of the lower motor neuron, whereas the dorsal root is composed of spinal ganglia and their cytoplasmic extension • sensory and motor neurons form a circuit that is important for reflex movements.

medulla oblongata

• contains the cardiac, vasomotor, and respiratory centers.

midbrain

• contains the visual and auditory reflex centers

Niemann-Pick disease

• deficiency of sphingomyelinase that leads to an accumulation of sphingomyelin • this disease also begins in childhood and is characterized by progressive mental deterioration. • The accumulation of sphingomyelin in the cytoplasm damages the cells. • Neuronal loss leads to profound atrophy of the brain.

Tay-Sachs disease

• deficiency of the enzyme hexosaminidase A • leads to accumulation of gangliosides in neurons • the disease presents early in life and is characterized by progressive mental and motor deterioration and blindness

Multiple sclerosis (MS) Pathology

• demyelinating disease that typically involves the white matter. • Demyelination of the axons leads to the formation of typical plaques that are usually found in the white matter of the brain, optic nerves, or spinal cord. • Periventricular plaques in the lateral hemispheres of the brain are typical. • Histologically, the early lesions are infiltrated with lymphocytes and macrophages. The older lesions consist of demyelinated axons surrounded by reactive astrocytes. • Oligodendroglial cells—the cells responsible for the myelination of axons—are remarkably absent, because they were most likely destroyed in the acute stages of the disease.

Myelitis

• diffuse infection of the spinal cord • like encephalitis, it is usually caused by viruses. • Poliomyelitis, a viral infection most prominently affecting the anterior horns of the spinal cord, was previously a major crippling disease, but it has been eradicated by immunization.

Neurosyphilis

• feature of tertiary syphilis, an infection with the sexually transmitted spirochete Treponema pallidum.

Global Ischemia

• found in patients who have widespread atherosclerotic narrowing of the entire cerebrovascular system • develop multiple foci of ischemic necrosis • such lacunar infarcts cause minor neurologic deficits but, over time, result in slowly progressive mental deterioration known as multiinfarct dementia

cerebrum

• has four major lobes: frontal, parietal, temporal, and occipital • frontal lobe primarily controls motor functions, but it also regulates behavior, emotions, and higher intellectual functions • parietal lobe has primarily sensory functions • occipital lobe is the seat of the visual center • temporal lobe has an important role in hearing and smelling

Atherosclerosis of the cerebral vessels

• has the same morphologic features as atherosclerosis in other sites • lesions may involve the major blood arteries or their intracerebral branches • narrowing of the arteries may be gradual, as a result of progressive atherosclerotic fibrosis and calcification, or it may occur suddenly, as when an atherosclerotic plaque ruptures, provoking intravascular thrombosis and complete occlusion of the arterial lumen.

thalamus

• important center for integrating sensory stimuli • important determinant of consciousness

dichotomy between the neurons and glia

• important for understanding the histogenesis of brain tumors • because the adult neurons are incapable of dividing, these cells never give rise to tumors • malignant tumors of neural cell origin are found only in children, in whom they presumably originate from undifferentiated precursors of neural cells, such as neuroblasts • primary tumors of the brain in adults are derived from glial cells and are classified as gliomas. • other support structures of the brain, such as the meninges and the blood vessels, also contain cells that are capable of proliferation and malignant transformation. These tumors are known as meningiomas or hemangioblastomas

Tuberculosis of the brain

• important in the past but is rare today.

Intracerebral Hemorrhage from Hypertension

• in patients who have no vascular anomalies, such as aneurysms, arteriovenous malformations, or hemangiomas, intracerebral hemorrhage or apoplexy is most often caused by arterial hypertension. • Hemorrhage results from the rupture of small blood vessels that have been damaged mechanically by hypertension. • The most common sites of hemorrhage are the basal ganglia, which are affected in about two-thirds of cases. • Cerebellar and pontine hemorrhage account for most of the remaining cases, whereas other sites are rarely involved. • With recent improvements in the treatment of hypertension, intracerebral hemorrhages have become less common. • Intracerebral hemorrhage typically results in a well-circumscribed hematoma that is clearly visible on CT scans of the brain • like infarcts, such hematomas are surrounded by edematous brain tissue. • Cerebral edema subsides in patients who survive the apoplexy, with resorption of the extravasated blood and the destruction of necrotic tissue by the hemorrhage. • Ultimately, the infarct transforms into a pseudocyst, which usually contains yellow fluid. The wall of the pseudocyst typically contains hemosiderin-laden macrophages.

Encephalitis

• inflammation of the brain • may present as (1) localized or (2) diffuse disease of cerebral parenchyma • most often is caused by viruses that invade neural or glial cells • Herpes simplex encephalitis usually affects the temporal lobe, causing foci of necrosis, and hemorrhage is the best example of a localized encephalitis. • Viral particles can be recognized in the nuclei of infected cells. • Epidemic, arthropod-borne viral encephalitides, such as West Nile virus encephalitis, is an example of a diffuse inflammation → typically, it is accompanied by widespread lymphocytic infiltrates that fill the perivascular Virchow-Robin spaces and can be readily recognized by microscopic examination of the brain at autopsy

Meningitis

• inflammation of the meninges. • Viral meningitis, probably the most common and most underdiagnosed infectious disease of the CNS, occurs in many viral diseases, such as the common flu. • characterized by a lymphocytic exudate in the subarachnoid space • viral encephalitis may also extend into the meninges → in such cases, microscopic CSF analysis reveals lymphocytosis. Typically, the protein content of CSF is also increased. • In contrast, bacterial meningitis caused by pyogenic bacteria, such as S. pneumoniae or N. meningitidis, is characterized by an exudation of neutrophils. • In severe cases the entire surface of the brain is covered with pus that fills the subarachnoid spaces → the CSF typically contains numerous neutrophils, a finding that is important in establishing the diagnosis. • like viral encephalitis, bacterial infection is associated with an increased protein content in the CSF. Glucose levels are, however, lowered, because most bacteria typically consume glucose in the CSF.

Neurons

• large, very complex cells that have highly specialized functions • each neuron has three basic components: a cell body, also known as a perikaryon; one or several dendrites; and a single axon • the perikaryon contains the nucleus, which is typically surrounded by a well-developed cytoplasm full of organelles • dendrites and axons are extensions of the cytoplasm that contain less organelles and that are specialized for the transmission of neural impulses • axons and dendrites form the cerebral and spinal tracts and the cranial and spinal nerves • neurons cannot regenerate

Ependymal cells

• line the inside of ventricles of the brain and the central canal of the spinal cord • the cilia on the apical surface of the ependymal cells contribute to the flow of CSF (Damjanov, 102016, p. 469)

Cerebral abscess

• localized suppurative infection of the brain • presents as a mass lesion and may be mistaken for a tumor • abscess consists of a cavity filled with pus and a capsule composed of glial cells and fibroblasts • most abscesses are caused by pyogenic bacteria, but in immunosuppressed patients, some abscesses may be of fungal origin or may contain mixed flora.

Spinal ganglia

• located external to the spinal cord, to which they are connected by the dorsal roots.

Subarachnoid hemorrhage

• located in the space between the arachnoid and the pia (i.e., the brain surface) • are caused most often by traumatic contusion of the brain, in which case the blood leaks into the subarachnoid space from the ruptured cerebral blood vessels at the base of the brain • ruptured aneurysms of the circle of Willis are another important cause of subarachnoid hemorrhages • congenital saccular aneurysms (berry aneurysms) are found in 1% to 2% of the general population, although most are clinically silent • rupture usually occurs between 30 and 60 years of age and can be precipitated by hypertension but often occurs spontaneously and without any obvious cause • bleeding into the subarachnoid space is associated with high mortality • if recognized, berry aneurysms can be treated surgically → clips are placed at the site of their origin, preventing the entry of blood into the lumen of the aneurysm.

sensory spinal tracts

• located predominantly in the posterior columns • represent the axonal extension of neurons located in the spinal ganglia

cerebellum

• major regulator of motor activities • controls the maintenance of balance, regulates the tone of muscles, and coordinates voluntary movement. • receives sensory input from the spinal cord and vestibular organ of the inner ear, as well as motor impulses from the cerebral cortex → these neural signals are integrated in the cerebellum and transmitted to the skeletal muscles to coordinate their function. • Damage of the cerebellum affects the coordination of limb and eye movements.

mass effects

• mass effects of tumors, cerebral abscesses, or hematomas are associated with localizing neurologic symptoms from compression or destruction of a part of the brain → a tumor my cause epileptic seizure by pressing on a cortical motor center.

clinical features of intracerebral hemorrhage

• may resemble those of cerebral infarction • in most cases the clinical picture is more dramatic, with about 30% of patients losing consciousness and appearing stricken • other patients may complain of severe headache or may experience an urge to vomit. • hemorrhage into the basal ganglia is accompanied by a rapid onset of hemiplegia and hemiparesis, which are fully developed in most patients admitted to the hospital. • Cerebellar hemorrhage typically presents with nausea and vomiting, loss of balance, and severe headache → Patients rapidly lapse into coma, and most die within 48 hours. • Pontine hemorrhages are almost invariably lethal, with most patients dying within hours of the onset of the first, usually nonspecific, symptoms

Multiple sclerosis (MS) Mediation

• mediated by (1) helper lymphocytes, (2) macrophages, and (3) B-cells and plasma cells. • T helper lymphocytes are classified as TH1 and TH17 T-cells → they react with myelin antigens and secrete cytokines. TH1 cells secrete IFN-γ, which activates macrophages, and TH17 cells promote the recruitment of inflammatory cells. • Oligoclona proliferations of sensitized T-cells, consistent with activation to several antigens, is considered to be the basis of MS lesions. The nature of these hypothetical antigens has not been elucidated. • Macrophages are prominent in MS brain lesions. • B-lymphocytes and plasma cells are found at the periphery of brain lesions, but their role is enigmatic. These antibody-producing cells and their precursors are usually found around the cerebral blood vessels near the lesion. Immunoglobulin G (IgG), secreted by these cells, is found in the CSF. By immunoelectrophoresis, it may be shown that the IgG in the CSF is composed of oligoclonal bands, suggesting that the B-cells in the brain also represent selected clones responding to some unidentified antigen. • Although the significance of all these immunologic findings remains uncertain, oligoclonal IgG bands in the CSF are useful in the diagnosis of MS.

Subdural Hematomas

• occupy the space between the dura and the arachnoid • normally this space is bridged by thin-walled veins that can be easily torn by trauma, especially the type of blunt trauma that causes sudden movement of the brain in one direction and the dura in another • typically found in boxers or in unattended, bedridden, elderly patients who have fallen out of bed. • Repeated trauma has a cumulative effect → it is thought that the sudden movement of the brain in one direction, if unaccompanied by a similar movement of the dura, has a tearing effect on the bridging veins and can rupture them • the coagulated blood typically covers the lateral hemispheres like a cap. • the symptoms are initially nonspecific (e.g., headache), but as the hematoma enlarges, it may produce significant neurologic symptoms, a loss of consciousness, and even death.

midbrain, pons, and medulla oblongata

• parts of the brain that contain numerous myelinated nerve bundles connecting the brain with the spinal cord • also contain important centers that regulate elementary body functions.

Schwann cells

• peripheral nerve equivalents of oligodendroglia • they form myelin sheaths of peripheral nerves

Autoimmune diseases of the CNS

• poorly understood • neuroimmunology is still a rather obscure field. • An immune form of encephalitis has been described in patients immunized against various infectious diseases • some late forms of postinfectious encephalitis may represent an immune disease.

Brain concussion

• presents as a transient loss of consciousness, usually after blunt head trauma • loss of consciousness is based on functional disturbances affecting the temporal lobes and the reticular activating system of the brainstem. • There are no significant macroscopic or microscopic changes in the brain.

Thiamine deficiency

• presents clinically as Wernicke's encephalopathy or Korsakoff's syndrome • Wernicke's syndrome includes disturbances in ocular function, gait, and mental function. • Korsakoff's syndrome presents with mental deterioration whereby patients lose memory (amnesia) and make up incredible stories (confabulation). • Degenerative neuronal changes are typically found in the hypothalamus, the periaqueductal region of the midbrain, and mamillary bodies. • These two syndromes are often combined and can be referred to as Wernicke-Korsakoff syndrome.

Fungal infections of the CNS

• reach the brain hematogenously • fungal encephalitis or meningitis is usually found in immunosuppressed patients and is especially common in those with AIDS • most important pathogens are Candida albicans, Aspergillus flavus, and Cryptococcus neoformans.

autonomous nervous system

• regulates involuntary (autonomic) body functions • consists of a sympathetic and a parasympathetic part • the nerve cells of the autonomic nervous system are located in the peripheral ganglia, which may be paravertebral or located at a distance from the CNS (collateral ganglia) • like the neurons in the CNS, autonomic nerve cells have axons that innervate various internal organs → regulates movement within the intestines, the tonus of blood vessels, urination, ejaculation, and many other automatic or reflux functions. • sympathetic stimulation causes vasoconstriction and hypertension, whereas parasympathetic stimuli have just the opposite effects.

chronic traumatic encephalopathy

• results from repetitive brain traumas in professional sports players, such as football or ice-hockey players and boxers • progressive disease usually presents in former athletes with neurologic and psychiatric symptoms such as memory loss, reduced mental capacity, confusion, uncontrollable rage, and aggressiveness or depression many years after they have ended their sports careers • some develop dementia and are fully mentally incapacitated

CSF Functions

• separate the brain from the meninges • serve as a mechanical buffer between the brain and the bones of the skull • venue for the disposition of metabolites and waste products from the brain • normally has a defined biochemical composition that fluctuates very little • rate of production, flow, and resorption of CSF remains constant under normal circumstances. Obstruction of CSF flow or blockage of CSF resorption leads to the accumulation of fluid in the brain (hydrocephalus).

hypothalamus

• serves as a crossroad that connects various parts of the brain • contains the centers for regulation of temperature, heart rate, blood pressure, thirst, appetite, and many others are located in the hypothalamus. • hypothalamic centers are the source of the neurosecretory substances that stimulate the pituitary to produce various trophic hormones regulating the function of other endocrine glands.

Oligodendroglial cells

• small cells that form long cytoplasmic processes that wrap around the axons.

Microglia

• small cells with short cytoplasmic processes • mobile, phagocytic, and are derived from bone marrow precursors that have colonized the brain

Prions

• small infectious particles composed of protein, causing so-called spongiform encephalopathies like kuru or Creutzfeldt-Jakob disease • previously classified as "slow viruses," prions seem to be distinct from viruses in that they do not contain DNA or RNA. • Prions infect the nervous system and eyes selectively and are transmitted by direct exposure to infected material, such as brain tissue or cornea • smallest infectious agents known so far • first described in 1982 • before that discoveryit was known that kuru, a prion-induced disease affecting the natives of New Guinea, was infectious → the aborigines of that area were cannibals who ate the brains of other people and the disease was transmitted by the infected brain tissue. • At highest risk were the women and children who ate human brains as a delicacy.

meninges

• specialized connective tissue that envelopes the brain • outer layer, called the dura, is composed of dense collagenous tissue • middle layer, called the arachnoid, is loosely structured and consists of loose connective tissue strands and blood vessels • innermost layer, called the pia, is contiguous to the brain and actually represents the external surface of the brain

Astrocytes

• star-shaped, relatively large cells with cytoplasmic processes that attach to nerves and blood vessels

basal ganglia

• supply inhibitory stimuli to skeletal muscles, coordinate skeletal muscle contractions, and block unwanted muscle contractions

Cerebrospinal Fluid (CSF)

• the brain is separated from the arachnoid by a thin space filled with cerebrospinal fluid (CSF), produced by the choroid plexus in the third ventricles • the fluid flows (under relatively low pressure) from the lateral ventricles into the third ventricle and then into the fourth ventricle • serves as a cushion that protects the brain from injury and allows an exchange of substances between the brain and the blood • in normal adults the volume of CSF is approximately 150 mL, and it circulates at a constant rate. • circulation of CSF depends on a constant rate of production and resorption (approximately 500 mL/day) (Damjanov, 2016, p. 469)

anencephaly

• the calvaria are not formed and the unprotected brain is destroyed in utero • incompatible with life • folic acid taken during pregnancy can reduce the occurrence of anencephaly and other dysraphic malformations.

Multiple sclerosis (MS)

• the most important of all immunologic disorders • demyelinating disease that is presumed to be of autoimmune origin. • most common immunologic CNS disease, affecting approximately 250 000 Americans, most of whom are 20 to 45 years of age. • has a prevalence of 1 in 1000 and is thus the leading neurologic disease in young adults • women are affected twice as often as men. • symptoms may appear at any age but rarely occur before puberty or after the age of 50 years.

motor tracts

• the motor tracts, such as the corticospinal tracts, are located in the anterior and lateral white matter → these myelinated nerves represent axonal extensions of cortical and subcortical neurons of the brain known as the upper motor neurons • axons of the cerebral nerves connect with distal neurons in the anterior horn of the spinal cord →called the lower motor neurons

glial cells (neuroglia)

• the support cells of the CNS are called glial cells (neuroglia) • glial cells are classified as astrocytes, oligodendroglia, microglia, and ependymal cells.

Cerebrovascular disease (CVD)

• the third most common cause of death and the most common crippling disease in the United States. • The most important clinical manifestation of CVD is stroke • strokes can be divided into two categories: (1) ischemic (85%), related to atherosclerosis of the cerebral arteries or thromboembolic occlusion of cerebral arteries, and (2) hemorrhagic (15%), most often representing a complication of arterial hypertension

Bacterial infections

• typically develop hematogenously, during sepsis and bacteremia or from septic emboli as in infectious endocarditis • bacterial infections of the paranasal sinuses or the middle ear also may spread into the cranium and cause CNS infection.

Epidural Hematoma

• typically located between the skull and the dura • this space under normal circumstances is almost nonexistent because of the close apposition of the dura to the skull bones • epidural hematoma develops from a ruptured middle meningeal artery most often torn by a bone spicule resulting from a fracture of temporal bone • because arterial blood fills the space, slowly separating the dura from the bone, it usually takes several hours before a large hematoma is formed • once the hematoma reaches a volume of 50 to 60 mL, it is large enough to compress the brain and cause coma • in children the skull bones are not as firmly fixated as in adults → arterial rupture can occur because of traumatic bone displacement, even without fracture • if unrecognized, epidural hematoma is invariably lethal. (Damjanov, 2016, pp. 473-474)

Protozoal infections of the CNS

• usually acquired hematogenously • most important protozoal pathogen is Toxoplasma gondii, an important cause of encephalitis in neonates • toxoplasmosis is also an important infection in patients with acquired immunodeficiency syndrome (AIDS) → clinical symptoms of toxoplasmosis evolve over a period of 1 to 2 weeks and may be both focal and diffuse • brain lesions may be seen by CT imaging as ring-enhancing lesions resembling those caused by lymphoma or fungal infections

rabies virus

• usually enters the human body through wounds inflicted by rabid dogs, foxes, or various other animals, such as raccoons and bats • in contrast to other viruses, the rabies virus reaches the CNS by traveling along the peripheral nerves from the site of inoculation through the spinal cord and specific neural pathways • Intracytoplasmic viral inclusions (Negri bodies) are found most prominently in the neurons of the brainstem • Symptoms typically appear 1 to 3 months after infection.

Neurosyphilis

• usually presents as chronic meningitis • the meninges are infiltrated with lymphocytes and plasma cells, which are typically centered on small blood vessels • in the healing stages of syphilitic infection, meningeal fibrosis predominates. • Fibrosis of the spinal meninges may compress the dorsal roots, resulting in atrophy of afferent, sensory axons entering the spinal cord → this causes the best-known complication of neurosyphilis: tabes dorsalis • tabes dorsalis is pathologically recognized on cross sections of the spinal cord by the atrophy of the dorsal (sensory) columns. • Syphilitic perivascular inflammation of the brain impairs the blood flow, causing ischemic necrosis of the cortical centers. The loss of neurons correlates clinically with motor and mental deterioration, collectively known as the syphilitic general paresis of the insane.

Viral Infections of the Brain

• usually spread to the brain by a hematogenous route • viral pathogens include common childhood viruses, such as the measles virus, rubella, or adenovirus. • The ubiquitous viruses, such as herpesvirus (HSV) or cytomegalovirus (CMV), may infect the brain of children or adults and cause either meningitis or encephalitis.

AIDS-related infections

• various pathologic forms of AIDS-related CNS lesions are sometimes combined and found in the same patient. • best illustrated by the so-called AIDS-related encephalopathy → a rather common finding in terminally ill patients infected with the human immunodeficiency virus (HIV). • HIV infects macrophages and T-lymphocytes, and these cells "import" the virus into the CNS. • The infected "newcomers" secrete various cytokines, some of which appear to be toxic to brain cells → AIDS dementia seems to be a consequence of these adverse influences • in addition, the HIV-infected brain is less resistant to invasion by a variety of bacterial, viral, parasitic, and fungal pathogens that rarely enter the normal brain. Among these pathogens, the most prominent are Toxoplasma and Cryptococcus. • Meningitis, encephalitis, or brain abscesses may develop. Most of these infections are resistant to treatment, and many patients die of CNS infection.