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Medical Microbiology. 4th edition.

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Chapter 96

Microbiology of the Nervous System


Richard T. Johnson.

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General Concepts

The anatomy of the brain and meninges determines the special character of central nervous system (CNS) infections. Epidural abscesses remain localized, whereas subdural abscesses spread over a hemisphere. Subarachnoid space infections spread widely over
the brain and spinal cord. The blood-brain barrier formed by the tight junctions between cells of the cerebral capillaries, choroid plexus, and arachnoid largely prevents macromolecules from entering the brain parenchyma. As a result, immunoglobulins and
immune-competent cells are scarce in the brain except at foci of inflammation. The space between cells in the brain parenchyma is too small to permit passage even of a virus. However, tetanus toxin and some viruses travel through the CNS by axoplasmic
flow.

Meningitis

Etiology

Major bacterial causes are Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Major viral causes are enteroviruses, mumps virus and lymphocytic choriomeningitis virus.

Pathogenesis

Most agents invade from blood. Bacteria grow rapidly in cerebrospinal fluid; viruses infect meningeal and ependymal cells.

Clinical Manifestations

Headache, fever and stiff neck are the symptoms of meningitis. Untreated bacterial meningitis is usually fatal; viral meningitis is benign. Cerebrospinal fluid findings are critical in differential diagnosis.

Treatment

Antibiotics are used to treat bacterial and fungal meningitis. Viral meningitis is treated symptomatically.

Brain Abscess

Etiology

Brain abscesses often exhibit a mixed flora of aerobic and anaerobic bacteria. Fungi are uncommon.

Pathogenesis

Abscesses begin when bacteria seed sites of necrosis, caused usually by infarction.

Clinical Manifestations

Headache, focal signs and seizures indicate a brain abscess. There are also characteristic computed tomography (CT) and magnetic resonance image (MRI) findings.

Treatment

Treatment consists of surgical drainage and appropriate antibiotics.

Encephalitis

Etiology

Many viruses cause mild meningoencephalitis; herpes simplex viruses and arboviruses are the major causes of potentially fatal disease.

Pathogenesis

Herpes simplex virus causes acute diffuse encephalitis in neonates. Herpes simplex type 1 causes focal temporal and frontal encephalitis in children and adults probably owing to invasion along olfactory or sensory nerves in the immune host. Arboviruses
invade from the blood and cause diffuse predominantly neuronal infection. Rabies invades along peripheral nerves.

Clinical Manifestations

Encephalitis causes headache, fever, CNS depression, seizures, and mononuclear cells in cerebrospinal fluid. Focal temporal lobe signs occur in herpes simplex virus encephalitis.

Treatment

Acyclovir is used to treat herpes simplex encephalitis. Some arboviruses can be prevented by mosquito control or vaccines.

Slow and Chronic CNS Infections

Spirochetes

Untreated syphilis and Lyme disease can cause varied later CNS disease.

Retroviruses

Human immunodeficiency virus can cause acute and progressive CNS disease. HTLV-I causes chronic spastic paraparesis in a small number of infected persons.

Conventional Viruses

Persistent measles and rubella virus infections can cause subacute encephalitis with dementia. JC virus, a papovavirus, can cause progressive demyelinating disease in immunodeficient patients.

Unconventional Agents

Kuru and Creutzfeldt-Jakob disease are chronic noninflammatory, degenerative diseases of the brain that are caused by unconventional agents called prions.

Parasites

Parasites may cause acute meningitis or encephalitis, chronic encephalopathy, and cerebral granulomas. Neurocysticercosis is the most common parasitic neurologic disease.

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Introduction

Infections of the nervous system are rare but life-threatening complications of systemic infections. The central nervous system (CNS) presents a special milieu for bacterial, fungal, viral and parasitic infections: the brain and spinal cord are protected
by bone and meningeal coverings that compartmentalize infection; they are divided by barriers from the systemic circulation; they lack an intrinsic immune system; and they have a unique compact structure.

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Gross Anatomy

The brain is protected by the bony calvaria, and the outer meningeal covering, the dura, is tightly bound to the bone. Epidural infections usually arise from bone infection (osteomyelitis) and remain localized (Fig. 96-1). At the foramen magnum the dura
becomes free, forming a true epidural space around the spinal cord. The dura and arachnoid are not adherent to each other. Consequently, when bacteria penetrate the dura into the subdural space, infection can spread rapidly over a cerebral hemisphere.
However, subdural empyema is usually confined to one hemisphere by the dural reflexions along the falx and tentorium. The subarachnoid space is a true space, containing cerebrospinal fluid (CSF) that flows from the ventricles to the basilar cisterns over
the convexities of the hemispheres and through the spinal subarachnoid space. The CSF contains little antibody or complement and few phagocytic cells. Therefore, bacteria that enter this space undergo an initial phase of logarithmic growth, accounting
for the often explosive onset of acute bacterial meningitis.

Figure 96-1. Anatomy and site of infection of the brain and spinal cord. Figure 96-1

Anatomy and site of infection of the brain and spinal cord. (Modified from Butler IJ, Johnson RT: Central nervous system infections. Pediatr Clin N Am 21:650, 1974, with permission.)
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Blood-Brain Barrier

Dyes such as trypan blue injected into the systemic circulation stain virtually all tissues, with the exception of the brain and spinal cord. This blood-brain barrier, which excludes most macromolecules and microorganisms, is due to the cellular
configuration of the cerebral capillaries, the choroid plexus, and arachnoid cells (Fig. 96-2). This barrier excludes not only most microbes, but most immunocompetent cells and antibodies. Therefore, although the barrier deters invasion of infectious
agents, it hampers their clearance once it is penetrated.

Figure 96-2. Blood-brain barrier.
Figure 96-2

Blood-brain barrier. Tight junctions envelop the CNS between capillary endothelial cells, choroid plexus epithelial cells, and arachnoid cells. The cerebral capillaries (A) lack fenestrations, have a dense basement membrane, and have tightly apposed
footplates (more...)
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Immune System

Antibodies found in the normal CNS are derived from the serum. Levels of IgG and IgA in the CSF are approximately 0.2 to 0.4 percent of the serum levels. Since diffusion of macromolecules across the barrier is largely size dependent, IgM is present at
even lower levels. There is also no lymphatic system in the usual sense, and few, if any, phagocytic cells. Complement is also largely excluded.

When trauma or inflammation disrupts the blood-brain barrier, antibody molecules passively leak into the CNS along with other serum proteins. When an inflammatory reaction has been mounted against an infection, B cells from the peripheral circulation can
move into the perivascular spaces of the CNS and generate immunoglobulins intrathecally.

Polymorphonuclear cells are the dominant inflammatory cells in acute bacterial infections of the CNS; they are attracted by chemotactic factors mediated primarily by components of complement activated by antibody-antigen reactions. Mononuclear cells are
the dominant inflammatory cells in viral infections and in subacute infections such as tuberculosis and fungal infections. In viral infections, specifically sensitized T-cells cross the blood-brain barrier into the CNS first, and lymphokines released by
these cells probably recruit the entry of B cells and macrophages.

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Cellular Structure

There is no brain-CSF barrier. The ependymal cells have no tight junctions, so the CSF in the ventricles and extracellular fluid in the brain are in direct contact. However, the cellular gap between neural cells measures only about 10 to 15 nm, less than
the diameter of even the smallest virus, and thus free movement of inflammatory cells or microorganisms within the extracellular space of the brain and spinal cord is restricted.

The highly specialized nature of neural cells is important in the pathogenesis of CNS infection. Different subpopulations of neurons have different surface receptors, which have been usurped by viruses to permit entry into cells. Furthermore, both
bacterial toxins and viruses can be carried by axoplasmic transport either into the CNS or within the CNS along the long axonal processes to distant but functionally linked neurons. Tetanus toxin, for example, is picked up in vesicles at peripheral axon
terminals and is carried to the neuron cell body within the CNS. Viruses, such as rabies, similarly are moved within the axon transport system (Table 96-1).

Table 96-1. Pathways of Spread to the Central Nervous System.
Table 96-1

Pathways of Spread to the Central Nervous System.
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Meningitis

Meningitis is an inflammation of the pia-arachnoid meninges. It can be caused by growth of bacteria, fungi, or parasites within the subarachnoid space or by the growth of bacteria or viruses within the meningeal or ependymal cells. Meningitis is a
diffuse infection caused by a variety of different agents (Fig. 96-3).

Figure 96-3. Major causes of acute meningitis (all ages, worldwide).
Figure 96-3

Major causes of acute meningitis (all ages, worldwide). “Other” viruses include herpes simplex virus type 2, arthropod-borne viruses, Epstein-Barr virus, influenza virus, and measles virus, as well as infections caused by Mycoplasma pneumoniae, (more.
..)
Etiology

Approximately 20,000 cases of bacterial meningitis occur in the United States each year. Seventy percent of these are in children younger than 10 years old. Infants are particularly susceptible because of their predisposition to bacterial infection,
possible lower integrity of barriers, and immature defense mechanisms. In neonates younger than 28 days old, meningitis is usually due to enteric bacilli (especially Escherichia coli), group B streptococci, or Listeria. Neonatal meningitis represents
fewer than 10 percent of cases of meningitis, but more than 50 percent of meningitis deaths. In the postnatal period, Haemophilus influenzae is the most common cause of bacterial meningitis, but this infection is largely limited to childhood. Significant
reductions in some countries are occurring due to use of capsular polysaccharide-protein conjugate vaccines during infancy. Adult bacterial meningitis is predominantly due to Neisseria meningitidis and Streptococcus pneumoniae, except in cases where
there had been a penetrating wound to the skull, surgery, or immunosuppression in the host. Neisseria meningitidis causes epidemic disease, all other forms of pyogenic meningitis are sporadic. Tuberculosis and fungi usually cause subacute meningitis.
Cryptococcus neoformans often causes meningitis in immunosuppressed patients, but can cause indolent meningitis in immunocompetent individuals. Coccidioides immitis and, rarely, other fungi also cause subacute meningitis.

Viral meningitis occurs more frequently than bacterial meningitis, with over 50,000 cases each year in the United States. The disease is benign and tends to be seasonal. Enteroviruses (echoviruses and coxsackieviruses) cause disease, primarily in the
late summer and early fall; mumps virus spreads predominantly in the spring; and lymphocytic choriomeningitis virus is more common in winter, since this virus is acquired from mice, which move indoors during cold weather and increase human exposure.

Pathogenesis

Most bacteria and viruses invade the CNS from the blood (Table 96-1), and the risk of CNS invasion has been shown to be related to the magnitude and duration of the bacteremia or viremia. Particles in the blood, including bacteria or viruses, are
normally cleared by the reticuloendothelial system, and speed of removal is proportional to size. The bacteria that maintain a bacteremia (and incidentally cause meningitis) are largely those which elaborate capsid polysaccharides that increase their
resistance to phagocytosis. Intracellular bacteria and a variety of viruses elude clearance by growing within blood cells. Enteroviruses and some arthropod-borne viruses (arboviruses) are cleared less effectively from serum because of their small size.
Some viruses enter the CNS by infecting endothelial cells or choroid plexus epithelium. Indeed, in mumps virus meningitis, choroid plexus cells containing viral nucleocapsids are frequently found within the CSF.

Clinical Manifestations

The primary clinical manifestations of meningitis are headache, fever, and nuchal rigidity (stiffness of the neck on passive forward flexion due to stretching of the inflamed meninges). Flexion of the neck may also cause reflex flexion of the legs (
Brudzinski sign), and meningeal irritation may limit extension of the leg when flexed at the knee (Kernig sign). Meningeal inflammation may also cause some degree of obtundation (reduced consciousness), and seizures are common in children. If bacterial
meningitis is not promptly treated, purulent material collects around the base of the brain, which may cause cranial nerve palsies and obstruct the flow of CSF, resulting in hydrocephalus. Vasculitis develops, with infarction of the brain and multifocal
neurological deficits. Untreated bacterial meningitis is a uniformly fatal disease. Viral meningitis, on the other hand, is benign and self-limited.

Systemic clinical signs sometimes suggest the agent (e.g., the rash or herpangina of enterovirus infections, the parotitis of mumps, or the multiple petechiae of meningococcemia). Examination of the CSF provides the most important diagnostic information (
Table 96-2). Acute bacterial infections evoke a polymorphonuclear cell response in the CSF and profound reductions of CSF sugar content. Bacteria can usually be seen on smears of the CSF and can be cultured if antibiotics have not been given. Subacute
tuberculous or fungal meningitis is more difficult to diagnose. The inflammatory response is usually composed of mononuclear cells, and the reduction of CSF sugar evolves slowly. Organisms are difficult to see on direct smears, although cryptococci may
be identified by mixing India ink with the CSF to outline the capsule of the organism and differentiate it from mononuclear inflammatory cells. In general, viruses produce a modest mononuclear cell response, and although the CSF protein may be elevated,
CSF sugar is normal or only mildly depressed. Viruses, such as enteroviruses and mumps virus, can be grown from the CSF, but this requires special viral cultures. A rapid diagnosis may be achieved by demonstrating antigen of various bacterial and fungal
agents or the presence of IgM against specific viral agents.

Table 96-2. CSF Findings in Nervous System Infections.
Table 96-2

CSF Findings in Nervous System Infections.
Treatment

Early diagnosis of bacterial and fungal meningitis and treatment with appropriate antimicrobial agents are crucial. The mortality rate due to untreated disease approaches 100 percent. Even with treatment, the death rate of individuals with acute
bacterial meningitis remains approximately 15%; it is as high as 30% for pneumococcal meningitis. Sequelae are frequent in survivors. This mortality and morbidity have remained relatively unchanged since the introduction of antibiotics. Further reduction
of death and disability rests primarily on the physician's early suspicion, diagnosis, and treatment of the disease. Viral meningitis requires only symptomatic treatment since the disease is self-limited; the prime management problem is to rule out
nonviral, treatable illnesses that can mimic acute viral meningitis (partially treatable bacterial meningitis, tuberculous or fungal meningitis, syphilis, Lyme disease, etc.).

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Infection of the Brain Parenchyma

Abscess

An abscess is a focus of purulent infection and is usually due to bacteria. Brain abscesses develop from either a contiguous focus of infection (such as the ears, the sinuses, or the teeth) or hematogenous spread from a distant focus (such as the lungs
or heart, particularly with chronic purulent pulmonary disease, subacute bacterial endocarditis, or cyanotic congenital heart disease). In many cases the source is undetected.

Etiology

Many brain abscesses have a mixed flora of aerobic and anaerobic bacteria. Approximately 60 to 70 percent contain streptococci; and Staphylococcus aureus, enterobacteria and Bacteroides are frequently present. Fungi cause fewer than 10 percent of brain
abscesses.

Pathogenesis

Abscesses in the brain parenchyma are thought to result from a bacterial seeding of already devitalized tissue. In experimental animals, direct injection of bacteria into the carotid arteries does not lead to brain abscess, whereas injection of
microspheres that occlude small vessels, followed by injection of bacteria does lead to abscess formation. With chronic purulent ear or sinus infection, infection extending along the veins may cause infarction of brain tissue; a bacterial abscess may
then evolve. In cyanotic congenital heart disease (right-to-left shunt), emboli cause small infarcts of the brain which are then seeded by bacteria from the blood.

Clinical Manifestations

The primary clinical manifestations of abscess are headache, focal signs, and seizures. The headache may not be severe, however, and the development of signs may be insidious. There may be no fever. If focal signs are present computed tomography (CT) or
magnetic resonance imaging (MRI) is performed rather than CSF examination. An abscess is identified by a hypodense area representing pus surrounded by an enhancing area representing the neovascularization and edema around the fibrous abscess wall. The
CSF is usually sterile, and bacteriologic diagnosis can only be obtained by culturing an aspirate of the abscess cavity.

Treatment

If a poorly defined area of cerebritis is found, treatment is begun with multiple antibiotics to cover the multiple common organisms. If there is encapsulation, the abscess should be drained to determine specific bacterial flora and prevent catastrophic
rupture of the abscess into the ventricles.

In contrast, epidural abscesses usually cause local pain and tenderness. Pressure against a localized area of the brain may lead to focal signs. Spinal epidural and cerebral or spinal subdural abscesses are surgical emergencies. Spinal epidural abscesses
have a rapid course, starting with segmental pain along nerve roots, followed by paresthesias of the body below the abscess level, and finally irreversible paraplegia. Subdural abscesses (subdural empyema) spread rapidly over a wider area. Subdural
empyema causes septic thrombosis of bridging veins, leading to hemiplegia and seizures (Fig. 96-1).

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Encephalitis

Encephalitis is defined as inflammation of the brain. Unlike an abscess, which is a localized area of bacterial or fungal growth, encephalitis is usually due to viruses that produce more widespread intracellular infections.

Etiology

Many viruses, including enteroviruses, mumps, and lymphocytic choriomeningitis viruses, cause mild forms of encephalitis. Life-threatening viral encephalitis is due primarily to herpes simplex viruses and arboviruses. Rabies virus causes uniformly fatal
infection, but no more than six cases have occurred in any year since 1979 in the United States.

Pathogenesis

The pathogenesis of encephalitis due to herpes simplex virus, arboviruses, and rabies virus is different for each virus. Herpes simplex viruses, both types 1 and 2 (HSV-1 AND HSV-2), cause encephalitis. In neonates, the disease is predominantly due to
HSV-2 virus, and irrespective of serotype, the acute generalized necrotizing encephalitis is often accompanied by evidence of systemic infection of the liver, adrenals, and other organs. In children and adults, however, encephalitis is caused by HSV-1
virus and is usually localized. This virus, which is acquired in childhood, remains latent within the trigeminal and other ganglia. It may reactivate to cause cold sores. Encephalitis in an immune host results either from the entry of a new virus,
possibly across the olfactory mucosa, or from reactivation of latent virus in the trigeminal ganglia, which spread along sensory nerve fibers to the base of the anterior and middle fossa. In either case, infection is localized to the orbital frontal and
medial temporal lobes. Because the host is immune, virus presumably spreads from cell to cell over a contiguous localized area, infecting neurons and glial cells.

In contrast, arboviruses (mainly togaviruses, flaviviruses, and bunyaviruses) spread to the brain from the blood. The systemic infection causes few, if any, symptoms. Depending on the virus, between 1 in 20 and 1 in 1000 infections are complicated by CNS
infection. The encephalitis is diffuse, but is localized largely to neurons.

Rabies, in contrast, is usually acquired through the bite of a rabid warm-blooded animal. This virus spreads by axonal transport from the inoculated skin or muscle to the corresponding dorsal root ganglion or anterior horn cells and then to populations
of neurons throughout the CNS. The early involvement of neurons of the limbic system cause the typical behavioral changes of clinical rabies. Polioviruses also show a selective infection of specific motor neuron populations which explains the
asymmetrical flaccid motor paralysis of poliomyelitis.

Clinical Manifestations

Herpes simplex virus-1 encephalitis in the non-neonate typically causes focal signs that may evolve over a period of up to 1 or 2 weeks. In addition to headache and fever, hallucinations and bizarre behavior are common, and these are sometimes confused
with psychiatric illness. Focal seizures and hemiparesis are frequent, and aphasia develops if the disease is localized to the dominant temporal lobe.

Arbovirus infections cause a more diffuse and acute disease, with a rapid depression of consciousness, greater frequency of generalized seizures, and multifocal signs. At times, however, this or any other form of encephalitis may localize to the temporal
areas, producing signs very similar to those of herpes simplex virus encephalitis.

The CSF examination in acute encephalitis may or may not show an increase in pressure, but usually reveals an inflammatory response of mononuclear cells. Examination early in disease may show no cellular response or a predominance of polymorphonuclear
cells. Red blood cells are frequently found in herpes encephalitis because of the necrotizing pathology of the disease, but they are not universally present nor are they specific to the disease. The CSF protein level is usually elevated and the CSF sugar
level remains normal. Cultures for herpes simplex virus are usually negative. Polymerase chain reaction tests for herpesvirus sequences are highly sensitive and specific in experienced laboratories. Intrathecal antiherpesvirus antibody may be detected
late in the course of the disease, but too late to instigate therapy. In most arbovirus infections, virus-specific IgM is present in spinal fluid, for specific diagnosis at the time of initial presentation.

The electroencephalogram (EEG) is helpful in the diagnosis of herpes simplex virus encephalitis because periodic spikes and slow waves often localize to the infected temporal lobe. In other forms of encephalitis slowing is more diffuse. Computerized
tomography in cases of herpes simplex virus encephalitis usually shows an attenuated area in the medial temporal lobes and sometimes a mass effect, but these findings, like the CSF and EEG changes, are not diagnostic. A prompt, definitive diagnosis of
HSV-1 encephalitis requires brain biopsy of the area where typical encephalitis with inclusion bodies is seen, and the diagnosis is confirmed by either immunocytochemical staining of herpes simplex virus antigens in brain cells or virus isolation.

Treatment

Rapid diagnosis of herpes simplex virus encephalitis is important because a specific antiviral therapy, acyclovir (acycloguanosine), reduces the mortality from 70 percent without treatment to 25 percent if treatment is initiated prior to the onset of
coma. Other forms of viral encephalitis are treated primarily with supportive care, although some arboviral encephalitides, such as Japanese encephalitis, can be prevented by vaccines, and others can be reduced by mosquito control.

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Slow and Chronic Infection and Chronic Neurologic Disease

Chronic nervous system infections, such as those that occur with syphilis, persist over many years with the unpredictable appearance of varied neurologic complications. In contrast, slow infections, such as Creutzfeldt-Jakob disease, have more
predictable incubation periods with a progressive buildup of infectivity, followed by a disease of predictable course lasting months or years. The slow infections resemble acute infections, with a predictable incubation period and disease course, but
extend over months or years. Chronic or slow neurologic diseases due to persistent infection must be differentiated from chronic diseases that represent the static sequelae of acute bacterial meningitis or viral encephalitis; the former are progressive
and depend on the ongoing replication of the infectious agent in the nervous system (Table 96-3).

Table 96-3. Slow and Chronic Infections of the Nervous System.
Table 96-3

Slow and Chronic Infections of the Nervous System.
Spirochetes

Syphilis can cause varied neurologic diseases over the lifetime of the untreated patient. During secondary syphilis, 6 weeks to 3 months after primary infection, a benign mild meningitis may accompany the primary CNS invasion that occurs in approximately
25 percent of untreated patients. Later complications include acute meningovascular inflammatory disease leading to stroke (meningovascular syphilis) 3 to 5 years after the primary infection, progressive dementia (general paresis) 8 to 10 years later, or
a chronic arachnoiditis involving primarily the posterior roots of the spinal cord (tabes dorsalis) 10 to 20 years after infection. This development of vasculitis, parenchymal involvement and chronic arachnoiditis parallel the complications that occur
over weeks during untreated bacterial meningitis. Lyme disease also may be complicated by early and late neurologic involvement. Mild meningitis and facial palsy often accompany the initial rash and systemic symptoms following the tickbite. In 15 percent
of untreated patients, subacute or recurrent meningitis, encephalitis, cranial nerve palsies, and peripheral neuropathies develop 1 to 9 months later, and rarely a chronic meningoencephalitis has been described years later.

Retroviruses

Two human retroviruses cause chronic neurological diseases. Human immunodeficiency virus (HIV) infects the CNS soon after systemic infection in most patients. An acute meningitis or acute demyelinating polyneuritis (Guillain-Barré syndrome) occasionally
occurs at the time of seroconversion and a recurrent meningitis and motor neuropathies can occur during the long, otherwise asymptomatic seropositive period. Years later at the time of clinical AIDS, dementia, myelopathy and a painful sensory neuropathy
are frequent.

In contrast, most persons infected with human T-cell lymphotropic virus type 1 (HTLV-I) suffer no neurologic disease. Less than 1 percent of those infected develop a slowly progressive myelopathy called tropical spastic paraparesis or HTLV-associated
myelopathy. This inflammatory disease of the spinal cord usually develops during the fourth or fifth decade of life even though HTLV-1 infection is most frequently acquired from breast feeding during the neonatal period.

In chronic spirochetal and retroviral infections the CSF often has a mild mononuclear cell inflammatory response, mild elevation of protein levels, and elevated IgG in an oligoclonal pattern, suggesting an ongoing infection.

Conventional Viruses

Some conventional viruses occasionally produce chronic disease. This outcome may result from defective replication of the virus or a defect in the host. Following uncomplicated measles, approximately one per million children develop subacute sclerosing
panencephalitis (SSPE) 6 to 8 years later. This chronic dementing illness with myoclonic movements is due to a defective measles virus infection in the CNS. Progressive multifocal leukoencephalopathy, in contrast, is due to a ubiquitous papovavirus, JC
virus, which infects almost all children without recognized symptoms. In immunodeficient patients, this virus may cause a subacute or chronic demyelinating disease of the brain with multifocal signs, leading to death usually in less than 6 months.
Rubella virus has been associated with chronic encephalitis after congenital infection, and, in very rare cases, there has been a relapse of a disease in adolescence resembling SSPE. In these infections the precise location of virus and the virus-host
relationship during the long incubation period is not known.

Unconventional Agents

Unconventional agents called prions or spongiform encephalopathy agents are transmissible but have no identified nucleic acid. Kuru, the first of these to be described, has been limited to an isolated population in New Guinea. Creutzfeldt-Jakob disease,
however, occurs worldwide. It is a presenile dementia with histopathologic abnormalities limited to the CNS; the brain shows vacuolization of neurons and glia, but no inflammatory response. The disease has a course of rapidly progressive cognitive
deficits with myoclonic movements. Death usually occurs in less than 6 months. In experimental infection with these agents, infectivity in the brain and extraneural tissues slowly accumulates during the long incubation period, but no immune response to
the agent is found in natural or experimental infection.

Parasites

Parasitic infections such as malaria, amebiasis with free-swimming amoebas and trichinosis can produce acute encephalopathy or meningitis. Others are associated with chronic disease, such as the chronic sleeping sickness of African trypanosomiasis, the
chronic cerebral granulomas caused by Schistosoma japonicum, or abscesses caused by Toxoplasma gondii in immunodeficient patients. The commonest parasitic neurologic disease is cysticercosis caused by the larvae form of Taenia solium. The parasitic cysts
and resulting basilar arachnoiditis are the most common causes of epilepsy and hydrocephalus in many areas of South America and Asia.

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References

Chun CH, Johnson JD, Hofstetter M. et al. Brain abscess: a study of 45 consecutive cases. Medicine. 1986;65:415. [PubMed]
Durand ML, Calderwood SB, Weber DJ. et al. Acute bacterial meningitis in adults. A review of 493 episodes. New Engl J Med. 1993;328:21. [PubMed]
Glass JD, Johnson RT: Human immunodeficiency and the brain. Ann Rev Neurosci, in press, 1995 .
Johnson RT: Viral Infections of the Nervous System. Raven Press, New York, 1982 .
Kennedy PGE, Johnson RT (eds): Infections of the Nervous System. Butterworths, London, 1987 .

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