It can be caused by a bacterial infection, such as bacterial meningitis, or may be a complication of a current infectious disease syphilis (secondary encephalitis).

Certain parasitic or protozoal infestations, such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune systems. Lyme disease or "Bartonella henselae" may also cause encephalitis.

Other bacterial pathogens, like "Mycoplasma" and those causing rickettsial disease, cause inflammation of the meninges and consequently encephalitis. A non-infectious cause includes acute disseminated encephalitis which is demyelinated.

Viral encephalitis can occur either as a direct effect of an acute infection, or as one of the sequelae of a latent infection. The majority of viral cases of encephalitis have an unknown cause, however the most common identifiable cause of viral encephalitis is from herpes simplex infection. Other causes of acute viral encephalitis are rabies virus, poliovirus, and measles virus.

Additional possible viral causes are arbovirus (St. Louis encephalitis, West Nile encephalitis virus), bunyavirus (La Crosse strain), arenavirus (lymphocytic choriomeningitis virus) and reovirus (Colorado tick virus). The Powassan virus is a rare cause of encephalitis.

A preceding antigenic challenge can be identified in approximately two-thirds of people. Viral infections thought to induce ADEM include influenza virus, enterovirus, measles, mumps, rubella, varicella zoster, Epstein Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, and coxsackievirus; while the bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci. The only vaccine proven to induce ADEM is the Semple form of the rabies vaccine, but hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been implicated. The majority of the studies that correlate vaccination with ADEM onset use small samples or case studies. Large scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination. In rare cases, ADEM seems to follow from organ transplantation. An upper bound for the risk of ADEM from measles vaccination, if it exists, can be estimated to be 10 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases. Some early vaccines, later shown to have been contaminated with host animal CNS tissue, had ADEM incident rates as high as 1 in 600.

The disease is associated with high rates of mortality and severe morbidity.

Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRS or EDSS), average time to recover is one to six months. The mortality rate may be as high as 5%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.

ADEM can progress to MS. It will be considered MS if some lesions appear in different times and brain areas

Herpesviral Encephalitis can be treated with high-dose intravenous acyclovir. Without treatment, HSE results in rapid death in approximately 70% of cases; survivors suffer severe neurological damage. When treated, HSE is still fatal in one-third of cases, and causes serious long-term neurological damage in over half of survivors. Twenty percent of treated patients recover with minor damage. Only a small population of survivors (2.5%) regain completely normal brain function. Indeed, many amnesic cases in the scientific literature have etiologies involving HSE. Earlier treatment (within 48 hours of symptom onset) improves the chances of a good recovery. Rarely, treated individuals can have relapse of infection weeks to months later. There is evidence that aberrant inflammation triggered by herpes simplex can result in granulomatous inflammation in the brain, which responds to steroids. While the herpes virus can be spread, encephalitis itself is not infectious. Other viruses can cause similar symptoms of encephalitis, though usually milder (Herpesvirus 6, varicella zoster virus, Epstein-Barr, cytomegalovirus, coxsackievirus, etc.).

Herpesviral encephalitis is encephalitis due to herpes simplex virus.

Herpes simplex encephalitis (HSE) is a viral infection of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year and some studies suggest an incidence rate of 5.9 cases per 100,000 live births. The majority of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. 57% of American adults are infected with HSV-1, which is spread through droplets, casual contact, and sometimes sexual contact, though most infected people never have cold sores. About 10% of cases of herpes encephalitis are due to HSV-2, which is typically spread through sexual contact. About 1 in 3 cases of HSE result from primary HSV-1 infection, predominantly occurring in individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately 50% of individuals who develop HSE are over 50 years of age.

Although for a long time, the cause of Mollaret's meningitis was not known, recent work has associated this problem with herpes simplex viruses, which cause cold sores, occular herpes as well as genital herpes.

Cases of Mollaret's resulting from varicella zoster virus infection, diagnosed by polymerase chain reaction (PCR), have been documented. In these cases, PCR for herpes simplex was negative.

Some patients also report frequent shingles outbreaks. Varicella zoster virus, which causes chickenpox and shingles is part of the herpes family, and is sometimes called "herpes zoster virus". CNS epidermoid cysts can give rise to Mollaret's meningitis especially with surgical manipulation of cyst contents.

A familial association, where more than one family member had Mollaret's, has been documented.

The virus is most often spread by person to person contact with the stool or saliva of the infected person. Two types of vaccines 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 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.

Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults. Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid, the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF. Meningitis caused by "H. influenzae" and meningococci has a better prognosis than cases caused by group B streptococci, coliforms and "S. pneumonia". In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.

In children there are several potential disabilities which may result from damage to the nervous system, including sensorineural hearing loss, epilepsy, learning and behavioral difficulties, as well as decreased intelligence. These occur in about 15% of survivors. Some of the hearing loss may be reversible. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).

Tuberculous meningitis in children continues to be associated with a significant risk of death even with treatment (19%), and a significant proportion of the surviving children have ongoing neurological problems. Just over a third of all cases survives with no problems.

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, pons, medulla and cerebellum of most infected patients. The infection can reach up through the thalamus and hypothalamus and possibly reach the cerebral hemispheres. The infection is caused by the poliomyelitis virus which is a single-stranded RNA virus surrounded by a non-enveloped capsid. 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.

Recurring Mollaret meningitis attacks will occur through the patient lifespan so long as the HSV virus is not managed. Patients have reported symptoms for as long as 30 years from first episode. Diet and stress management are key to keeping the HSV virus at bay.

Meningoencephalitis (; from Greek μῆνιγξ "meninx", "membrane", ἐγκέφαλος, "enképhalos" "brain", and the medical suffix "-itis", "inflammation") is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.

Although meningitis is a notifiable disease in many countries, the exact incidence rate is unknown. In 2013 meningitis resulted in 303,000 deaths – down from 464,000 deaths in 1990. In 2010 it was estimated that meningitis resulted in 420,000 deaths, excluding cryptococcal meningitis.

Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually. Sub-Saharan Africa has been plagued by large epidemics of meningococcal meningitis for over a century, leading to it being labeled the "meningitis belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave can last two to three years, dying out during the intervening rainy seasons. Attack rates of 100–800 cases per 100,000 are encountered in this area, which is poorly served by medical care. These cases are predominantly caused by meningococci. The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.

Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, college campuses and the annual Hajj pilgrimage. Although the pattern of epidemic cycles in Africa is not well understood, several factors have been associated with the development of epidemics in the meningitis belt. They include: medical conditions (immunological susceptibility of the population), demographic conditions (travel and large population displacements), socioeconomic conditions (overcrowding and poor living conditions), climatic conditions (drought and dust storms), and concurrent infections (acute respiratory infections).

There are significant differences in the local distribution of causes for bacterial meningitis. For instance, while "N. meningitides" groups B and C cause most disease episodes in Europe, group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented meningococcal meningitis cases.

Prevention strategies include reducing the breeding of midges through source reduction (removal and modification of breeding sites) and reducing contact between midges and people. This can be accomplished by reducing the number of natural and artificial water-filled habitats and encourage the midge larvae to grow.

Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.

One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction. This study revealed that OROV caused central nervous system infections in three patients. The three patients all had meningoencephalitis and also showed signs of clear lympho-monocytic cellular pattern in CSF, high protein, and normal to slightly decreased glucose levels indicating they had viral infections. Two of the patients already had underlying infections that can effect the CNS and immune system and in particular one of these patients has HIV/AIDS and the third patient has neurocysticercosis. Two patients were infected with OROV developed meningitis and it was theorized that this is due to them being immunocompromised. Through this it was revealed that it's possible that the invasion of the central nervous system by the oropouche virus can be performed by a pervious blood-brain barrier damage.

Survivors of "Haemophilus" meningitis may experience permanent damage caused by inflammation around the brain, mostly involving neurological disorders. Long-term complications include brain damage, hearing loss, and mental retardation. Other possible long-term effects are reduced IQ, cerebral palsy, and the development of seizures. Children that survive the disease are more often held back in school, and are more likely to require special education services. Negative long-term effects are more likely in subjects whose treatments were delayed, as well as in subjects who were given antibiotics to which the bacteria was resistant. Ten percent of survivors develop epilepsy, while close to twenty percent of survivors develop hearing loss ranging from mild loss to deafness. About 45% of survivors experience no negative long-term effects.

The theory of autoimmune attack claims that a person with neuroimmunologic disorders have genetic predisposition to auto-immune disorder, and the environmental factors would trigger the disease. The specific genetics in myelitis is not completely understood. It is believed that the immune system response could be to viral, bacterial, fungal, or parasitic infection; however, it is not known why the immune system attacks itself. Especially, for immune system to cause inflammatory response anywhere in the central nervous system, the cells from immune system must pass through the blood brain barrier. In the case of myelitis, not only is the immune system dysfunctional, but the dysfunction also crosses this protective blood brain barrier to affect the spinal cord.

Most viral myelitis is acute, but the retroviruses (such as HIV and HTLV) can cause chronic myelitis. Poliomyelitis, or gray matter myelitis, is usually caused by infection of anterior horn of the spinal cord by the enteroviruses (polioviruses, enteroviruses (EV) 70 and 71, echoviruses, coxsackieviruses A and B) and the flaviviruses (West Nile, Japanese encephalitis, tick-borne encephalitis). On the other hand, transverse myelitis or leukomyelitis, or white matter myelitis, are often caused by the herpesviruses and influenza virus. It can be due to direct viral invasion or via immune mediated mechanisms.

Bacterial myelitis includes "Mycoplasma Pneumoniae", which is a common agent for respiratory tract. Studies have shown respiratory tract infections within 4–39 days prior to the onset of transverse myelitis. Or, tuberculosis, syphilis, and brucellosis are also known to cause myelitis in immune-compromised individuals. Myelitis is a rare manifestation of bacterial infection.

Fungi have been reported to cause spinal cord disease either by forming abscesses inside the bone or by granuloma. In general, there are two groups of fungi that may infect the CNS and cause myelitis - primary and secondary pathogens. Primary pathogens include the following: "Cryptococcus neoformans", "Coccidioides immitis", "Blastomyces dermatitides", and "Hystoplasma capsulatum". Secondary pathogens are opportunistic agents that primarily infect immunocompromised hosts such as Candida species, Aspergillus species, and zygomycetes.

Parasitic species infect human hosts through larvae that penetrate the skin. Then they enter the lymphatic and circulatory system, and migrate to liver and lung. Some reach the spinal cord. Parasitic infections have been reported with Schistosoma species, "Toxocara canis", Echinococcus species, "Taenia solium", "Trichinella spiralis", and Plasmodium species.

The number of new cases a year is unknown. According to the California Encephalitis Project, the disease has a higher incidence than its individual viral counterparts in patients younger than 30. The largest case series to date characterized 577 patients with anti-NMDA receptor encephalitis. The epidemiological data were limited, but this study provides the best approximation of disease distribution. It found that women are disproportionally affected, with 81% of cases reported in female patients. Disease onset is skewed toward children, with a median age of diagnosis of 21 years. Over a third of cases were children, while only 5% of cases were patients over the age of 45. This same review found that 394 out of 501 patients (79%) had a good outcome by 24 months. 30 patients (6%) died, and the rest were left with mild to severe deficits. The study also confirmed that patients with the condition are more likely to be of Asian or African origin.

Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:

- "Acute disseminated encephalomyelitis" or "postinfectious encephalomyelitis", a demyelinating disease of the brain and spinal cord, possibly triggered by viral infection.

- "Encephalomyelitis disseminata", a synonym for multiple sclerosis.

- "AntiMOG associated encephalomyelitis", one of the underlying conditions for the phenotype neuromyelitis optica and in general all the spectrum of MOG autoantibody-associated demyelinating diseases.

- "Equine encephalomyelitis", also called "equine encephalitis", a potentially fatal mosquito-borne viral disease that infects horses and humans.

- "Myalgic encephalomyelitis", a disease involving presumed inflammation of the central nervous system with symptoms of muscle pain and fatigue; the term has sometimes been used interchangeably with "chronic fatigue syndrome", though there is still controversy over the distinction.

- "Experimental autoimmune encephalomyelitis" (EAE), an animal model of brain inflammation.

- Progressive encephalomyelitis with rigidity and myoclonus (PERM) – A kind of stiff person syndrome.

- AIDS related encephalomyelitis, caused by opportunistic Human T-lymphotropic virus type III (HTLV-III) infection.

Because it is a bacterial disease, the primary method of treatment for "Haemophilus" meningitis is anti-bacterial therapy. Common antibiotics include ceftriaxone or cefotaxime, both of which can combat the infection and thus reduce inflammation in the meninges, or the membranes that protect the brain and spinal cord. Anti-inflammatories such as corticosteroids, or steroids produced by the body to reduce inflammation, can also be used to fight the meningeal inflammation in an attempt to reduce risk of mortality and reduce the possibility of brain damage.

Given that some conditions as MS show cortical damage together with the WM damage, there has been interest if this can appear as a secondary damage of the WM. It seems that some researchers claim so.

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" as the most common cause of inflammatory disease of the canine CNS. The disease is more common in female toy dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord. The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent. One study searched for viral DNA from "canine herpesvirus", "canine adenovirus", and "canine parvovirus" in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis (see below for the latter two conditions), but failed to find any.

Demyelination is produced by injection of brain extracts, CNS proteins (such as myelin basic protein), or peptides from such protein emulsified in an adjuvant such as complete Freund's adjuvant. The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides. In many protocols, mice are coinjected with pertussis toxin to break down the blood-brain barrier and allow immune cells access to the CNS tissue. This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.

Although sharing some features, mostly demyelination, this model, first introduced in 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities; animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge.