Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

, which is an

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

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 ...

of the

meninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

, and

encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...

, which is an infection or inflammation of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

Signs and symptoms

Signs of meningoencephalitis include unusual behavior,

personality changes Personality Changes: Originally thought to be concrete and unchanging, recent studies have found evidence that personality can change throughout a person's life. An important idea to keep in mind is that differences in personality traits among ind ...

, and thinking problems. Symptoms may include

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

, pain in neck movement,

light sensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity ...

, and

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

Causes

Causative organisms include

protozoan Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...

viral Viral means "relating to viruses" (small infectious agents). Viral may also refer to: Viral behavior, or virality Memetic behavior likened that of a virus, for example: * Viral marketing, the use of existing social networks to spread a marke ...

and

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

s. Specific types include:

Bacterial

Veterinarians have observed meningoencephalitis in animals infected with listeriosis, caused by the pathogenic bacteria '' L. monocytogenes''. Meningitis and encephalitis already present in the brain or spinal cord of an animal may form simultaneously into meningeoencephalitis. The bacterium commonly targets the sensitive structures of the brain stem. ''L. monocytogenes'' meningoencephalitis has been documented to significantly increase the number of

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

, such as

IL-1β Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...

, IL-12, IL-15, leading to toxic effects on the brain. Meningoencephalitis may be one of the severe complications of diseases originating from several ''

Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The term "rickett ...

'' species, such as ''

Rickettsia rickettsii ''Rickettsia rickettsii'' (abbreviated as ''R. rickettsii'') is a gram-negative, intracellular, coccobacillus bacterium that is around 0.8 to 2.0 μm long. ''R. rickettsii'' is the causative agent of Rocky Mountain spotted fever. ''R. rickettsii ...

'' (agent of Rocky Mountain spotted fever (RMSF)), ''

Rickettsia conorii ''Rickettsia conorii'' is a Gram-negative, obligate intracellular bacterium of the genus ''Rickettsia'' that causes human disease called boutonneuse fever, Mediterranean spotted fever, Israeli tick typhus, Astrakhan spotted fever, Kenya tick ty ...

'', ''

Rickettsia prowazekii ''Rickettsia prowazekii'' is a species of gram-negative, alphaproteobacteria, obligate intracellular parasitic, aerobic bacillus bacteria that is the etiologic agent of epidemic typhus, transmitted in the feces of lice. In North America, the ...

'' (agent of epidemic louse-borne typhus), and ''

Rickettsia africae ''Rickettsia africae'' is a species of ''Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long) ...

''. It can cause impairments to the cranial nerves, paralysis to the eyes, and sudden

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

. Meningoencephalitis is a rare, late-stage manifestation of tick-borne ricksettial diseases, such as RMSF and human monocytotropic ehrlichiosis (HME), caused by ''

Ehrlichia chaffeensis ''Ehrlichia chaffeensis'' is an obligate intracellular, Gram-negative species of Rickettsiales bacteria. It is a zoonotic pathogen transmitted to humans by the Amblyomma americanum, lone star tick (''Amblyomma americanum''). It is the causative ...

'' (a species of rickettsiales bacteria). Other bacteria that can cause it are '' Mycoplasma pneumoniae'',

Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

, '' Borrelia'' (

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the ''Borrelia'' bacterium, which is spread by ticks in the genus ''Ixodes''. The most common sign of infection is an expanding red rash, known as erythema migran ...

) and

Leptospirosis Leptospirosis is a blood infection caused by the bacteria ''Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, severe ...

Viral

Tick-borne encephalitis Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis or meningoencephalitis. Myelitis and spinal paralysis also occurs. In about one third ...

West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...

Measles Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

* Varicella-zoster virus * Enterovirus *

Herpes simplex virus type 1 Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral infe ...

Herpes simplex virus type 2 Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral infe ...

* Rabies virus *

Adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...

, although meningoencephalitis is almost solely seen in heavily immunocompromised patients. *

Mumps MUMPS ("Massachusetts General Hospital Utility Multi-Programming System"), or M, is an imperative, high-level programming language with an integrated transaction processing key–value database. It was originally developed at Massachusetts Gener ...

, a relatively common cause of meningoencephalitis. However, most cases are mild, and mumps meningoencephalitis generally does not result in death or neurologic

sequelae A sequela (, ; usually used in the plural, sequelae ) is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word, meaning “sequel”, it is used in the medical field to mean a complication ...

. *

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

, a very small number of individuals exhibit meningoencephalitis at the primary stage of infection.

Autoimmune

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 ...

targeting

amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s which have been used during research on

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. * Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibodies, which are also associated with seizures and a movement disorder, and related to

anti-NMDA receptor encephalitis Anti-NMDA receptor encephalitis is a type of encephalitis, brain inflammation caused by antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with delusions, false b ...

. * NAIM or "Nonvasculitic autoimmune inflammatory meningoencephalitis" (NAIM). They can be divided into GFAP- and GFAP+ cases. The second is related to the autoimmune GFAP astrocytopathy.

Protozoal

* '' Naegleria fowleri'' ( percolozoa) * ''

Trypanosoma brucei ''Trypanosoma brucei'' is a species of parasitic Kinetoplastida, kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclus ...

'' (

euglenozoa Euglenozoa are a large group of flagellate Discoba. They include a variety of common free-living species, as well as a few important parasites, some of which infect humans. Euglenozoa are represented by three major clades, i.e., Kinetoplastea, Di ...

) * ''

Toxoplasma gondii ''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...

'' ( apicomplexa)

Animal

* ''

Halicephalobus gingivalis ''Halicephalobus gingivalis'' is a free-living saprophagous nematode species identified and named in 1954 by Stefanski. It is a facultative parasite of horses, invading the nasal cavity, and sometimes numerous other areas, where it produces gran ...

'' This

nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...

is an exceptionally rare cause of meningoencephalitis.

Other/multiple

Other causes include

granulomatous meningoencephalitis Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by ''canine distemper virus'' a ...

and

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused b ...

. The fungus, ''

Cryptococcus neoformans ''Cryptococcus neoformans'' is an encapsulated yeast belonging to the class Tremellomycetes and an obligate aerobe that can live in both plants and animals. Its teleomorph is a filamentous fungus, formerly referred to ''Filobasidiella neoformans' ...

'', can be symptomatically manifested within the CNS as meningoencephalitis with

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...

being a very characteristic finding due to the unique thick

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...

capsule of the organism.

Diagnosis

Clinical diagnosis includes evaluation for the presence of recurrent or recent herpes infection, fever, headache, altered mental status, convulsions, disturbance of consciousness, and focal signs. Testing of cerebrospinal fluid is usually performed.

Treatment

Antiviral therapy, such as acyclovir and ganciclovir, work best when applied as early as possible. May also be treated with

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...

as an immune therapy. Symptomatic therapy can be applied as needed. High fever can be treated by physical regulation of body temperature. Seizure can be treated with

antiepileptic drug Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

s. High intracranial pressure can be treated with drugs such as mannitol. If caused by an infection then the infection can be treated with

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

drugs.

References

External links

{{CNS diseases of the nervous system Encephalitis Meningitis Central nervous system disorders Herpes simplex virus–associated diseases