polioencephalitis
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Polioencephalitis is a viral infection of the brain, causing inflammation within the grey matter of the brain stem. The virus has an affinity for neuronal cell bodies and has been found to affect mostly the
midbrain The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
,
pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Va ...
,
medulla Medulla or Medullary may refer to: Science * Medulla oblongata, a part of the brain stem * Renal medulla, a part of the kidney * Adrenal medulla, a part of the adrenal gland * Medulla of ovary, a stroma in the center of the ovary * Medulla of th ...
and
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
of most infected patients. The infection can reach up through the
thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and
hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
and possibly reach the
cerebral hemispheres The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...
. The infection is caused by the
poliomyelitis Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sym ...
virus which is a single-stranded, positive sense
RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...
surrounded by a non-enveloped
capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
. Humans are the only known natural hosts of this virus. The disease has been eliminated from the U.S. since the mid-twentieth century, but is still found in certain areas of the world such as Africa.


Signs and symptoms

Signs and symptoms may vary and some individuals may not experience any symptoms at all. The most common reported symptom of polioencephalitis is fatigue. Fatigue is associated with difficulty in attention, cognition, and maintaining wakefulness Some individuals experience psychiatric symptoms that include anxious mood,
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
,
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, and depressed mood. Confusion and disorientation of time and space have also been reported. Motor symptoms vary more from patient to patient, but can include incoordination and tremors,
nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...
, loss of conjugate
eye movements Eye movement includes the voluntary or involuntary movement of the eyes. Eye movements are used by a number of organisms (e.g. primates, rodents, flies, birds, fish, cats, crabs, octopus) to fixate, inspect and track visual objects of inte ...
, rigidity and
hemiparesis Hemiparesis, or unilateral paresis, is weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused ...
.


Mechanism

The
poliomyelitis Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sym ...
virus is an
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it ma ...
that enters through the mouth and multiplies in the throat and
epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
of the gastrointestinal tract. It will then move to the bloodstream and is carried to the central nervous system. Once in the CNS, the virus will attach to a host cell by binding with a cell surface receptor. The host cell surface receptor is a
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
that has been recently identified as CD155. Once the virus has bound to the host cell, it will penetrate the host cell membrane and begin the replication of its
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. Many cells contain the surface receptor CD155; however, manifestation of this disease does not occur in all cells. The reason for incidence of the disease in only certain areas of the brain such as the brainstem is unknown. Once areas of the brain have been invaded by the virus,
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
will occur. During inflammation, the brain’s tissues become swollen due to the body’s immune system response to the infection. Fluid, white blood cells, dead cellular debris and inactivated viruses resulting from the actions of the immune response can significantly alter the fluid surrounding healthy neurons. The function of these healthy neurons can decline due to disruptions in the cell membrane affecting electrical properties of the neuron or by interfering with the blood supply causing
anoxic The term anoxia means a total depletion in the level of oxygen, an extreme form of hypoxia or "low oxygen". The terms anoxia and hypoxia are used in various contexts: * Anoxic waters, sea water, fresh water or groundwater that are depleted of diss ...
cellular damage. Depending on which neurons are damaged will result in a variety of different symptoms.


Diagnosis

If someone is suspected of having polioencephalitis a sample of throat secretions, stool or
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
is checked for the virus. Blood tests can be done to detect
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against viral
antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
and foreign proteins. Virus isolation is the most sensitive method and it is most likely to be isolated from stool samples. Once isolated,
RT-PCR Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase cha ...
is used to differentiate naturally occurring strains from vaccine-like strains.


Prevention

The virus is most often spread by person to person contact with the stool or saliva of the infected person. Two types of
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
have been developed to prevent the occurrence and spread of the poliomyelitis virus. The first is an inactivated, or killed, form of the virus and the second is an attenuated, or weakened, form of the virus. The development of
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
has successfully eliminated the disease from the United States. There are continued vaccination efforts in the U.S. to maintain this success rate as this disease still occurs in some areas of the world.


Treatment

There is no cure for polioencephalitis so prevention is essential. Many people that become infected will not develop symptoms and their prognosis is excellent. However, the prognosis is dependent on the amount of cellular damage done by the virus and the area of the brain affected. Many people that develop more severe symptoms can have lifelong disabilities or it can lead to death. Supportive treatments include bed rest, pain relievers, and a nutritious diet. Many drugs have been used to treat psychiatric symptoms such as
Clonazepam Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat seizures, panic disorder, anxiety disorders, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine clas ...
for insomnia and
Desvenlafaxine Desvenlafaxine, sold under the brand name Pristiq among others, is a medication used to treat depression. It is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class and is taken by mouth. It is recommended that the ...
or
Citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and socia ...
for depressed mood.


Recent research

Research into the mechanism of this disease stalled with the development of the vaccines in the mid-twentieth century. However, with the recent identification of the cell surface receptor CD155 new interest has resurfaced in this disease. Experiments on transgenic mice are investigating the initial sites of viral replication in the host and how the virus moves from the bloodstream into the central nervous system. Research into the host range of the virus has also been of interest. The host range of a virus is determined by the interaction of the virus with host cellular receptors such as CD155. Comparison of the amino acid sequence in the binding domain of the host cell receptor is highly variable among mammalian species. Rapid changes in the sequence of the binding domain have restricted the host range of the poliovirus. Targeting of the brain and spinal cord have also come under investigation. The restricted tropism maybe due to organ specific differences in the initiation of
translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
by the virus internal
ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
entry site.


References

{{Use dmy dates, date=April 2017 Encephalitis