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What is encephalitis? What is acute encephalitis syndrome?

Encephalitis means inflammation of the brain. It is made up of two words, where “encehalon”- refers to the brain and “itis” refers to the inflammation. It is a condition where the brain becomes swollen as a part of the defense response towards infections and toxins.

It is different from meningitis where the protective covering present around the brain gets inflamed (swollen).

Acute encephalitis syndrome (AES) is a serious medical condition where a person develops acute fever along with mental issues like confusion, disorientation, delirium, or coma. The person may also develop seizures along with fever. The condition of the person may worsen rapidly leading to death in several hours or a few days.

Commonest cause of encephalitis in India is a viral infection. Other causes include bacteria, parasites, fungus, spirochetes, chemicals, and toxins.

Commonest virus to cause encephalitis in India is the Japanese encephalitis virus. The states like Uttar Pradesh (UP), Bihar, West Bengal, Assam, and Tamil Nadu are considered as Japanese encephalitis endemic zones.

Acute encephalitis syndrome is associated with a high number of deaths where up to 30% of patients suffering from the disease can die. There are also high chances of permanent brain-related complications and physical disability which may account for 30-50% of all cases of encephalitis.

In India, it also tends to occur in the form of outbreaks with multiple people developing the disease in a short span of time.

Japanese encephalitis mostly affects children, as the majority of the adults in endemic areas develop natural immunity post-childhood infection. However, it may occur at any age and may affect adults especially older adults with low immunity.

In many cases, no cause of encephalitis can be identified. In India, some of the recurrent epidemics of unknown cause have also occurred.

The treatment of encephalitis usually consists of symptomatic support with the maintenance of vitals.

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How many people suffer from acute encephalitis syndrome?

Most of the cases of encephalitis in Asian countries have been found to be due to Japanese encephalitis virus. It is estimated to cause encephalitis in 68,000 people each year globally, where it causes death in about 14,000-20,000 people.

National Vector Borne Diseases Control Programme (NVBDCP), found that 10,485 people developed acute encephalitis syndrome in India in the year 2018, out of which 632 people died. These cases were reported from 17 states with majority cases from Uttar Pradesh, Bihar, Jharkhand, Assam, Karnataka, Manipur, Meghalaya, Tripura, Tamil Nadu. Prior to this, about 11,651 cases were reported in India in 2016, out of which 1301 people died. In 2016, over 125 children died in a single hospital in Gorakhpur, UP. Most recently, an outbreak of encephalitis in June 2019, killed 154 children in Muzaffarpur, Bihar.

What are the causes of acute encephalitis?

Encephalitis can be caused by a variety of micro-organisms, chemicals, or toxins. However, in many cases, the cause remains unknown.

Virus: Amongst the known causes of encephalitis, the viral infection is the commonest cause. In Asia and India, the commonest virus is the Japanese encephalitis virus, other viruses that caused outbreaks were Chandipura virus (CHPV), Nipah virus (NiV), and other enteroviruses. Herpes simplex virus, Influenza A virus, West Nile virus, mumps, measles, dengue, Parvovirus B4 have also been found to cause encephalitis. Other micro-organisms: less commonly bacteria such as S.pneumoniae, scrub typhus and others, fungus, parasites, etc.

Chemical or Toxins: Hypoglycin A and methylene cyclopropylglycine (MCPG) found in litchi fruit have been postulated to cause the outbreak of AES in malnourished children of Muzaffarpur, leading to hypoglycemia and death in about 154 children.

What are the risk factors for the development of acute encephalitis?

There are several factors that have been found to be associated with more number of cases of acute encephalitis. These are as follows:

• Childhood: encephalitis can occur at any age. However, it is more common in children below 15 years of age. Elderly people are also more prone to develop encephalitis, especially people with pre-existing conditions and reduced immunity.

• Malnourishment: it has been found to be a predisposing factor in the development of encephalitis, especially seen as an important factor in the latest outbreak of 2019, which affected malnourished children in Muzaffarpur.

• Weakened immunity: this makes a person unable to fight infection and develop encephalitis.

• Endemic areas: encephalitis has been found to occur more often in certain regions.

South-east Asian countries including India are considered endemic zones for the Japanese encephalitis virus.

Within India, states in the Gangetic planes such as Uttar Pradesh (UP), Bihar, West Bengal, and Assam along with Tamil Nadu are considered as Japanese encephalitis endemic zones.

Chandipura virus is endemic in regions of Nagpur district in Maharashtra, eastern parts of Gujarat and Andhra Pradesh.

Nipah virus was seen affecting Bangladesh and West Bengal in India.

Seasonal outbreaks: encephalitis has been usually found to occur in the form of outbreaks, during a particular time of the year. Several outbreaks have been seen to occur in months of September to November. The last Muzaffarpur outbreak occurred during the litchi plucking season of the month of May and June which experienced an intense heatwave.

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What are the signs and symptoms of acute encephalitis?

Most of the cases of Japanese encephalitis show no apparent symptoms or mild symptoms such as:

• Fever

• Headache

• Body pain

• Weakness

However, about 1 in 250 people getting infected may develop severe disease with the following symptoms:

• Headache

• Neck stiffness

• Rapid onset of fever

• Confusion

• Disorientation

• Seizures

• Agitation, or hallucinations

• Loss of sensation or paralysis of the body

• Inability to talk

• Loss of consciousness

In infants and young children, following additional signs and symptoms that could be seen are:

• Bulging at the soft spots of infants skull (fontanels)

• Nausea and vomiting

• Body stiffness

• Poor feeding

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When to seek immediate medical help

Any person who develops a fever in a short span of time (less than 7 days) along with changes in mental status such a confusion, disorientation, loss of consciousness, abnormal behavior, or seizures may suggest significant signs and symptoms of encephalitis and should contact the doctor immediately.

What are the complications of acute encephalitis?

The condition affects the brain and can lead to significant physical & mental impairment which may account for 30-50% of all cases. The complications could be:

• Recurrent seizures

• Memory loss

• Vision problems

• Hearing problem

• Behavioral and intellectual problems

• Paralysis

• Coma

• Death- encephalitis is associated with a high death rate of up to 30% (Case Fatality Rate or CFR).

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How acute encephalitis is diagnosed?

To confirm the diagnose of AES and to find out the cause, the National Vector Borne Disease Control Programme (NVBDCP) India, has laid down certain diagnostic criteria. It has also established a countrywide surveillance program for AES with a focus on detecting Japanese encephalitis (JE).

What is the diagnostic workup for encephalitis?

Clinical history: For diagnosing encephalitis the doctors start with a thorough clinical history noting down the geographical and temporal relation to an epidemic.

Physical examination: Following this general physical and neurological examination would be done:

Use of clinical criteria: On the basis of clinical criteria established by NVBDCP (discussed above), the doctor would classify a person as a suspected case of encephalitis. This would be followed up by laboratory tests to establish the diagnosis of encephalitis and other tests for evaluating the condition of the person and to aid in diagnosis.

1. Laboratory tests which could be done in AES for the detection of JE virus are as follows:

• Antibody detection: these are the tests done to detect antibodies that body forms against the Japanese encephalitis virus. These are:

– Enzyme-Linked Immuno-Sorbent Assay (ELISA) for IgG (paired) and IgM (MAC) antibodies

– Haemagglutination Inhibition Test (HI),

– Complement Fixation Test (CF) etc.

• Antigen Detection: RPHA, IFA, Immunoperoxidase, etc.

• Genome Detection – RTPCR

• Isolation – Tissue culture, Infant mice, etc

In view of the limitations associated with various tests, IgM ELISA is the method of choice provided samples are collected 3-5 days after the infection.

2. Other tests:

• Brain imaging: MRI or CT scan of the brain can be done to check for the extent of the disease or to rule out any other condition such a hemorrhage, infarct, or tumor. It may also suggest the cause of encephalitis in some cases such as herpes encephalitis, where typically inferior frontal and temporal regions of brain are involved. MRI is considered more sensitive than a CT scan. The imaging should be done prior to lumbar puncture for CSF examination.

• CSF examination: Lumbar puncture is done to take out a small sample of cerebrospinal fluid (CSF), which is the fluid that circulates in and around the brain and spinal cord. The sample is taken for laboratory tests to look for any changes and to establish the diagnosis.

• Electroencephalogram (EEG): this test is done to read electric impulses generated by the activity of the brain cells. Here electrodes are put over the head which collects these impulses and shows it in the form of patterns. An abnormal pattern of electrical activity may indicate a diagnosis of encephalitis.

• Other lab investigations: basic laboratory tests to assess the general condition of the body and various organs such as blood routine, kidney function tests, urine examination, or throat swab.

• Brain biopsy: could be done in few cases to confirm the diagnosis or rule out other causes, especially in cases where the symptoms are worsening and treatment is not helping. Here a small brain tissue is taken out and is sent for testing.

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