Encephalitis - The Causes

Encephalitis is defined as a condition of irritation and swelling (inflammation) of the brain, as a result of virus, bacteria and others invasion.
A. Causes
1. Encephalitis caused by virus
a. Rabies virus 
Rabies virus is the etiological agent of an acute encephalitis, which in absence of post exposure treatment is fatal in almost all cases. In the study to analyze the role of the immuno-inhibitory molecule B7-H1 in this virus strategy, show that the B7-H1/PD-1 pathway can be exploited locally and in an organ specific manner--here the nervous system--by a neurotropic virus to promote successful host invasion(7).

b. Herpes simplex 
Herpes simplex encephalitis (HSE) is a life-threatening consequence of herpes simplex virus (HSV) infection of the central nervous system (CNS). Although HSE is rare, mortality rates reach 70% in the absence of therapy and only a minority of individuals return to normal function, according to Scientist at the University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center(8).

c. Poliovirus
Poliovirus virion RNA contains a single covalently bound sequence of polyadenylic acid which is approximately 49 nucleotides long. A single, slightly longer polyadenylic acid sequence is contained in Eastern Equine Encephalitis virus RNA(9).

d. Measles virus
There are report from The Hospital for Sick Children that a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease, as a brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscop(11).

e. JC virus
Scientist at the Karolinska Institute, Huddinge University Hospital showed that JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF) samples from patients with progressive multifocal leukoencephalopathy (PML) but not in CSF samples from patients with herpes simplex encephalitis, enteroviral meningitis, or multiple sclerosis. This suggests that inflammatory processes in the brain do not necessarily reactivate JCV, which further supports the proposal that the presence of JCV DNA in the CSF is diagnostic for PML(12)

f.  Japanese encephalitis virus
Japanese encephalitis virus (JEV) has found to be a pathogen causing febrile syndrome, encephalitis, and death. Envelop (E) glycoprotein is the major target of inducing neutralizing antibodies and protective immunity in host(13)

g.  West Nile encephalitis virus
WNV disseminates to the central nervous system (CNS) and causes severe disease primarily in the immunocompromised and elderly. Experimental studies have made significant progress in dissecting the viral and host factors that determine the pathogenesis and outcome of WNV infection.(14).

h.  Eastern equine encephalitis virus (EEE virus)
The eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories, according to University of Texas Medical Branch(15).

i. Etc.

2. Encephalitis caused by bacteria infection
a. Bacterial meningitis, such as herpes simplex virus
Health records from 2002 to 2006 of all children 6 months to 6 years with a discharge diagnosis from the Hospital for Sick Children (Toronto, ON) of febrile convulsion, meningitis, or encephalitis were reviewed. Rates of bacterial meningitis and HSV encephalitis in children presenting with complex febrile seizures were calculated(16). In the article of "Meningitis and Encephalitis: Introduction", the author(s) wrote "Inflammation of the meninges (meningitis) and inflammation of the brain (encephalitis) often are seen simultaneously (meningoencephalitis) in the same animal, although either can be seen separately. In animals with meningoencephalitis, the clinical signs of meningitis often precede the clinical signs of encephalitis and may remain the predominant feature of the illness"(17)

b.Syphilis
According to a report by centre hospitalier universitaire  17-year-old patient presented for one year progressive dementia, frontal syndrome and extra pyramidal syndrome. The cerebral CT scan showed a diffuse cortical and subcortical atrophy. Blood and CSF positive antibodies confirmed the diagnosis of late congenital meningoencephalitis due to syphilis(18)
 
3. Parasites and Others
a. Toxoplasmosis
Toxoplasmosis is a rare but rapidly fatal complication that can occur following hematopoietic stem cell transplantation (HSCT), according to Kyushu University Graduate School of Medical Sciences, in a study of over a 17-yr period at our institutions, two patients received a conventional conditioning regimen followed by transplantation from an HLA-matched donor; however, they developed severe graft-vs.-host disease, which required intensive immunosuppressive therapy. Despite prophylactic treatment with trimethoprim/sulfamethoxazole, their immunosuppressive state, as indicated by a low CD4(+) cell count, might have resulted in toxoplasmosis encephalitis.(19)
 
b. Malaria  
Malaria is a mosquito-borne infectious disease and associated Encephalitis to. In the article of "Mosquitoes and Diseas" posted in Illinois department of Public Health wrote "Today, however, the threat of developing encephalitis from mosquitoes is far greater than the threat of malaria in the United States. Encephalitis, meningitis and other diseases can develop from the bites of mosquitoes infected with certain viruses. These include the viruses of West Nile, St. Louis encephalitis, LaCrosse (California) encephalitis, and Eastern equine and Western equine encephalitis"(20)

c. Primary amoebic meningoencephalitis
Primary amoebic meningoencephalitis (PAM or PAME) is a disease of the central nervous system caused by infection from Naegleria fowleri. In the report of Dayanand Medical College and Hospital (DMC & H), a 36-year-old, Indian countryman who had a history of taking bath in the village pond. Computerized tomography (CT) scan of brain showed a soft tissue non-enhancing mass with erosion of sphenoid sinus. However CSF findings showed no fungal or bacterial pathogen. Trophozoites of Naegleria fowleri were detected in the direct microscopic examination of CSF and these were grown in culture on non-nutrient agar(21).

d. Lyme disease 
Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection(22).

e. Cryptococcus neoformans 
 reported from the Ohgaki Municipal Hospital., a 46-year-old man with hepatoma was admitted with chief complaints of headache, fever and dizziness. On admission, cerebellar signs (disturbance of finger-to-nose test and of heel-to-knee test, intention tremor, and truncal ataxia) were neurologically noted.  Head CT showed swelling and enhancement of the cerebellar cortex and dilatation of the cerebral ventriculi. Cryptococcus neoformans was detected in a culture of the patient's CSF.(23)

f. Streptococci 
Encephalitis lethargica or von Economo disease is an atypical form of encephalitis. Also known as "sleepy sickness" (though different from the sleeping sickness transmitted by the tsetse fly)(24)

g. Staphylococci 
In the study in 1997, 4,409 cases of meningitis and 632 cases of encephalitis were reported in Poland. Meningitis incidence rate was 11.4 per 100,000, and was 3-times lower than in 1996. The etiology of meningitis cases was as follows: 2,713 (61.5%) were due to viral agents (ECHO 30 dominated), 1,351 (30.7%) were caused by bacterial agents: 144 meningococcal (3.3%) and 1,207 other bacterial. The bacterial etiology was following: 33.2% were due to Streptococcus pneumoniae, 27.6% were cased by Haemophilus influenzae type b, and 11.6% by Staphylococci.(25)

h. Autoimmune disease 
Autoimmune limbic encephalitis is a rare disorder, characterised by the subacute onset of seizures, short-term memory loss, and psychiatric and behavioural symptoms. Initially, it was recognised as a paraneoplastic disorder, but recently a subgroup of patients without systemic cancer was identified. This type of limbic encephalitis is associated with voltage-gated potassium channel (VGKC) or N-methyl-D-aspartate receptor (NMDAR) antibodies(26).

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Sources
(7) http://www.ncbi.nlm.nih.gov/pubmed/18490751
(8) http://www.ncbi.nlm.nih.gov/pubmed/15319091
(10) http://www.ncbi.nlm.nih.gov/pubmed/4338097
(11) http://www.ncbi.nlm.nih.gov/pubmed/10589903
(12) http://www.ncbi.nlm.nih.gov/pubmed/9542955
(13) http://www.ncbi.nlm.nih.gov/pubmed/22544685
(14) http://www.ncbi.nlm.nih.gov/pubmed/19273254
(15) http://www.ncbi.nlm.nih.gov/pubmed/19889755
(16) http://www.ncbi.nlm.nih.gov/pubmed/19633589
(17) http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/101600.htm
(18) http://www.ncbi.nlm.nih.gov/pubmed/12829337
(19) http://www.ncbi.nlm.nih.gov/pubmed/17680814
(20) http://www.idph.state.il.us/envhealth/pcmosquitoes.htm
(21) http://www.ncbi.nlm.nih.gov/pubmed/18822627
(22) http://www.ncbi.nlm.nih.gov/pubmed/21648354
(23) http://www.ncbi.nlm.nih.gov/pubmed/1934783
(24) http://en.wikipedia.org/wiki/Encephalitis_lethargica
(25) http://www.ncbi.nlm.nih.gov/pubmed/10402851
(26) http://www.ncbi.nlm.nih.gov/pubmed/22510418