Encephalitis

Encephalitis is a potentially life threatening inflamation of the brain. It is usally caused by viral infections but may be aquired through bacterial infections or as a complication from another disease.

Two Forms There are two main forms of encephalitis, primary and secondary encephalitis. In primary encephalitis the virus directly invades the brain and spinal cord. However, in secondary encephalitis the virus will invade the body and then work its way to the brain.

From 1917-1928 an outbreak of encephalitis called Encephalitis Lethargica occured. Ecephalitis Lethargica may sometimes cause catatonia. This 1920's epidemic was caused by an autoimmune response. It was depicted in Dr. Oliver Sacks book, Awakenings.

Symptoms
Adults There are many different symptoms associated with encephalitis. The most common include fever with headache, vomitting, confusion, drowsiness, and photophobia. Less commonly occuring symptoms are muscle fatigue, seizures, and stiffness of neck. Occasionally certain portions of the body will be affected due to the location of inflamation on brain. IN the most severe cases respiratory arrest, mental impairment, coma, death may occur. In Young Children and Infants Usually young children will exhibit different symptoms than those seen in adults. Young children experience irratibility, anorexia, fever, and photophobia. The most common sign in infants are bulging fontanels.

Contractability
There are a variety of ways one may contract encephalitis. The most common of these are insenct bites, typically from mosquitos. Common childhood diseases such as mumps, measles, and rubella often cause encephlitis, as well as Varicella-zoster Virus, the chicken pox and shingles virus. Rabies from animal bites can lead to encephalitis if not properly treated. Herpes simplex virus is another likely cause. A strand of the herpes virus that may turn into mono, Epstein-barr Virus, may also lead to encephalitis. Although encephalitis cannot be contracted directly from another person, the virues that cause encephalitis may be contracted from another. Encephalitis is also a common effect of central nervous system disorders such as Multiple Sclerosis, Alzheimers, and Parkinson's disease.

Risks Factors that may increase a person chance of contracting encephalitis include age, weakened immune system, geographic regions, being outdoors, and the current season.

Diagnosis
A person may be diagnosed with encephalitis through a spinal tap, an electroencehpalogram (EEG), brain imgaing, brain biopsy, or blood testing. Lumbar Puncture or Spinal Tap: In a spinal tap fluid is collected from space around the spinal column. In encephalitis spinal taps may be used to isolate the virus.  Brain Imaging: CT scans or MRI, Magnetic Resonance Imaging, may be used to take pictures of the brain. MRIs have been the best choice for diagnosis when herpes is the cause of encephalitis. EEG: electroencehpalograms measure the electrical activity in the brain. This technique is commonly used with herpes, since a certain electrical pattern is seen. Brain Biopsy: A small portion of the brain is removed.

Mechanism
Inflammation due to encephalitis is almost always case specific. An exact mechanism is hard to identify since different mechanisms are seen with the causes for the disease. Here a simplified explanation of the inflammatory response in the brain is given. When a foreign invader enters the CNS, the brain initiates an inflammatory response. A major contributor to this response is microgila. Microgila are the white blood cells of the brain and account for a large portion of cells in the brain, second to neurons (Chew, 2006). At the site of injury, these cells will be the first to respond. Microglia, when stimulated change shape and perform a number of functions that further the inflammatory response. Micrcoglia cells may be stimulated by trauma, disruption of tissue, or release of intercellular contents. The microglia release cytokines and leukocytes that are both involved in inflammation maintenance. Cytokines, according to Chew et al, recruit other ceullar elements to the site of inflammation to help in its repair. The actual mechanism is very complex involving many second messenger systems. A major messenger system that is believed to be involved is MAP kinases (Fernandes et al, 2006). MAPK are second messengers systems that once activated will initiate the phosphorlyation of many products down the line. This leads to activation of other enzymes needed within the cell response.

Treatment
Treatment for encephalitis is usually symptomatic. Antibiotics for the viral infection are given and inflammation of the brain disappears with the destruction of the virus. Less specificlaly rest and healthy diet can help a person recover. Researchers are currently investingating the effects of interferon therapy, which seems to inhance the immune system. Herpes and Varicella-zoster When herpes or Varicella-zoster are the cause of endephalitis Zovirax is the drug of choice. It is typically given intravenously in the hospital for 10 days.

Current Research
Current research for encephalitis is difficult due to many factors. These include how hard the brain is to access, the blood-brain barrier for interaction of drugs, and the complexity of the brain. Because the most common and prolonged (without death) encephalitis cases are those of CNS diseases, these are the main focus of current research. In one study, the CNS disease, Multiple Sclerosis was used to investigate new therapies and the brain's own repairs. When in anitmoicrobial mode, tissue-damagingmode, the imflamation of the brain damages myelin and axons. In attempts to repoar itself the brain turns on counter-regulatory inflammatory mechnisms. Martino states that stimulation of these mechanisims may be more successful than any chemical interventions. Stimulants for repair of inflamation include injections of stem cells, T-cells, or an injection of protection cells that were converted from marcophages. Specific mechanisms were not given but all are thought to stimulate repair. Martino concludes that with these advances in treatment this may be the "natural reparative medicine" era. Although Martino belives natural repair is the best solution, Sundrarahan (et al) think PPAR-gamma could be a therapeutic drug for CNS disorders. PPAR-gamma is a nuclear receptor that stands for preoxisome proliferator-activated receptor gamma. Nuclear receptors directly bind to DNA to regulate gene expression. PPAR-gamma, when activated, is known to be an anit-inflammatory. It will repress transcription (gene expression)of inflammatory genes. Although all of this is true, Sundararajan (et al) admits after all their studies that much more research must be concuded about the specific mechanisms of PPAR-gamma before it can be used. Potts(et al) also worked with anit-inflammatories. Here the focus was minocycline, which reduces inflamation and neronal apoptosis. its beneficial effects seemed to be productive in mice with MS and Huntington's disease. The drug, however has negative effects such as tooth discoloration and alterations of bone growth in children. The conclusion of their studies called for further in depth research. Whether it be natural restoration, stimulation or drug intervention, researchers have a solid start on reducing inflamation of the brain. However, most agree that there is a copieous amount of work needed to truely understand not only interventions for decreasing inflamation but the brain and its mechanisms.