Meningitis and Encephalitis

Viral Meningitis

This is the most common cause of meningitis and tends to be less serious than the bacterial form and is rarely life threatening. In addition, viral meningitis cannot cause blood poisoning (septicaemia) which is usually life threating if left untreated. It commonly affects children under the age of 5 and those with a weak immune system. In the UK, viral meningitis is more widespread during the summer and autumn months. It is not known how many people get viral meningitis each year in the UK as most cases are mild and not reported. However it is estimated that there are many thousands of cases each year.

Viruses that can cause meningitis are:

• Enteroviruses (viruses that live in your intestine)
• Herpes Simplex Virus
• Mumps virus
• Ebstein Barr virus
• Human immunodeficiency virus (HIV)
• Cytomegalovirus (CMV)

Bacterial Meningitis

Bacterial meningitis is a medical emergency. Cases can arise suddenly, with symptoms worsening within hours to a couple of days and so it is usually acute. Rapid identification and treatment is crucial. The bacteria that cause bacterial meningitis can also spill into the blood and then multiply causing septicaemia (blood poisoning). If this occurs, organs such as the kidneys and liver can be affected and it can also cause damage to the limbs. Therefore, untreated bacterial meningitis is usually fatal. However, bacterial meningitis can also be caused by septicaemia where the bacteria in the blood stream enter the brain and cause it to be infected. Therefore meningitis can occur with or without septicaemia.

Children under the age of 4 seem to be at most risk of bacterial meningitis as well as teenagers aged 15-19 years of age. Every year around 2,500 cases of bacterial meningitis occur in the UK. While this condition can be caused by many different types (species) of bacteria, the most common causes are:

• Neisseria meningitidis – called meningococcal meningitis. This is the most common form in the UK and it is highly contagious. There are several different strains, but most cases in the UK are caused by strain B. Strain C used to be common, but vaccination now prevents most of these cases. Meningococcal bacteria are common. It is estimated that about 10% of the population carry them in the back of the nose or throat. Carriage is less common in young children than in adults. Young adults have the highest rate of carriage, with up to one in four harbouring the bacteria. As well as infecting the meninges, meningococcal bacteria can also cause septicaemia. This may be called meningococcal septicaemia. It is commonly seen in college/university students, infants, children, international travellers, and the immunocompromised.
• Streptococcus pneumoniae – called pneumococcal meningitis. This is the second most common cause of bacterial meningitis in the UK. According to a study in 2005, approximately half of pre-school children carry pneumococcal bacteria in the back of their nose and throat. These bacteria are therefore passed around by coughing, sneezing and close contact. In most cases carrying these bacteria is harmless. However in susceptible people these bacteria can cause a variety of illnesses including minor illness such as ear and sinus infections as well as life threating illnesses such as pneumonia and meningitis. Occasionally, pneumococcal meningitis can develop from a milder form of the infection such as earache. Infants under 2 years old and those with compromised immune systems are at greatest risk for it. A pneumococcal vaccine which protects against 13 strains of the bacteria is now given as part of the routine immunisation programme in the UK. It protects against some forms of pneumococcal meningitis but not all. Pneumococcal meningitis can result in septicaemia but not as often as in meningococcal meningitis.
• Haemophilus influenzae type b – once the most common cause of bacterial meningitis, its incidence has decreased because of widespread vaccination of children.
• Group B streptococcus, Escherichia coli, and Listeria monocytogenes are the most common causes of meningitis in the neonate (babies less six weeks old) and may be passed from the mother to her baby.

Chronic Meningitis

Chronic meningitis is meningitis symptoms that last for more than 4 weeks. Again it can be caused by infections but other non-infective causes such as connective tissue disease and malignancy may also be the cause. In up to a third of cases no cause is found. The most common cause of chronic meningitis is Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). This accounts for 40–60% of cases. However, other bacterial causes include Treponema pallidum which causes syphilis. Meningococcal bacteria rarely cause chronic meningitis. Other infective causes include fungi and parasites. Fungal meningitis is most commonly seen in immunocompromised patients, such as those with HIV/AIDS, but it may affect anyone. The most common fungal cause is Cryptococcus neoformans (cryptococcal meningitis), which is found in dirt and bird droppings. Other fungal causes include Coccidioides immitis, Histoplasma capsulatum, and Candida species. Amoebic meningitis is rare and can be lethal. It is caused by the free-living amoeba, Naegleria fowleri, a single-cell parasite, which can be found in warm water lakes and rivers.

Meningitis may also be recurrent. There is a rare condition called Mollaret’s meningitis which is a recurrent form of meningitis. It is thought to be caused in many cases by an infection with a member of the herpes family of viruses. Patients with this condition usually experience viral meningitis more than once and are often given acyclovir to prevent recurrence if the cause turns out to be the herpes virus. Recurrent meningitis is more common in patients with immune deficiencies or underlying structural defects in the brain.

Encephalitis is an inflammation of the brain characterised by fever, headache, and an altered state of consciousness, with or without seizures. Encephalitis itself is not common however, and it is estimated that there are 4000 new cases of encephalitis in the UK every year. The symptoms may be very mild and in view of this there are probably many more cases with mild symptoms that occur but are not documented.

Viruses are the most common cause of encephalitis. However, other infectious organisms may be involved and it can also be caused by non-infectious causes such as by the autoimmune system attacking the brain. The herpes simplex virus is the most common cause of encephalitis in the UK. The herpes zoster virus that causes chickenpox is also common. Other common viruses involved are enterovirus, the mumps virus and the Epstein-barr virus. Rarely, other viruses may be involved such as the rabies virus (from an animal bite), or arboviruses. Arboviruses are usually spread by insects such as infected mosquitoes or ticks. Therefore, throughout the world where other insects may be more common, different types of arbovirus-related encephalitis may be seen.

Bacterial, fungal, and parasitic encephalitis are very rare. Bacterial meningoencephalitis may develop from the bacteria that cause meningitis. Tick-transmitted Lyme disease may cause bacterial encephalitis as can mycobacterium tuberculosis which causes TB. Toxoplasma gondii, a parasite associated with cats, can cause parasitic encephalitis in some people with compromised immune systems. Other bacteria, fungi, and parasites can occasionally cause encephalitis.

There are two types of encephalitis, primary and secondary. In primary encephalitis, the brain and spinal cord are infected directly. The infection may be limited to a single location (focal) or be spread throughout the brain (generalised). Secondary encephalitis, also known as post-infective encephalitis, can result from complications of a current or previous viral infection. In these cases the auto-immune system which normally fights off the virus can start attacking the brain. It can also be caused by the same reaction of the auto-immune system to a vaccination or a tumour. Post-infectious and autoimmune/inflammatory encephalomyelitis are broadly represented by the syndrome called acute disseminated encephalomyelitis (ADEM). In this syndrome the inflammation damages a special protective sheath around the nerve fibres called myelin. This damages the nerve fibres and can cause loss of function of certain parts of the body supplied by these nerves, in addition to the general features of headache and fever. ADEM is more common in children.

In addition, encephalitis can also be divided into acute and chronic. The acute form is more common. However, chronic encephalitis can occur where the inflammation occurs slowly over months. This can be caused by the HIV virus however it can be caused also be caused by other unknown causes.

Meningitis and encephalitis may start with flu-like symptoms and intensify over a few hours to a few days. Initial symptoms that can be common to both are:

• Fever ( usually >38°C)
• Headache
• Nausea and vomiting
• Joint pain

After this the symptoms usually become more typical for the individual disease. However, affected individuals may not have all of these symptoms and someone can still have either of the two diseases with very few symptoms. Common symptoms of meningitis include:

• Neck stiffness
• sensitivity to bright lights
• confusion
• fits
• a rash
• severe arm or leg pain

As meningitis can also present with septicaemia there may be other features present.

The symptoms of septicaemia include:

• sudden onset of a high fever
• being sick
• pale or blotchy skin
• difficulty breathing
• shivering or having cold hands and feet
• aching limbs or joints
• a rash
• drowsiness, confusion or loss of consciousness

The typical septicaemic rash of meningitisis red/purple and doesn’t go away when the bottom of a glass is pressed onto it (the tumbler test). However, this is usually a late sign of meningitis and it is not always present. Other, non septicaemic rashes can be present in meningitis which may look different. In addition, the rash of viral meningitis may also look different to this. Therefore it is important to pay attention to any rash you see and report it to a doctor.

Encephalitis on the other hand usually presents with:

• headache
• fever
• altered consciousness

Encephalitis symptoms may also include neurological problems: difficulty with hearing or speech, involuntary eye movements, such as moving the eyes from side to side, loss of sensation, partial paralysis, seizures, hallucinations, muscle weakness, changes in personality, and coma. Other symptoms that overlap with meningitis may also occur such as sensitivity to bright light and a stiff neck.

It is also important to be aware that not all cases show all these classical signs. Elderly patients for example may be simply lethargic and show few other signs. Patients with compromised immune systems may have atypical symptoms and be harder to diagnose. Infants tend to have different symptoms to older children. As such they may be irritable and cry when they are held, vomit, be stiff or very floppy,, have seizures or jerky movements and refuse food. When examined they mayhave bulging fontanelles (the soft spots on the top of the head) and pale or blotchy skin.

As the early signs of meningitis or encephalitis may present very similarly to flu with non-specific symptoms such as fever and malaise it is important that early signs are reported to medical staff. This is particularly important as patients with meningitis can rapidly deteriorate.

Complications and Prognosis
The outcome of those with meningitis and encephalitis depends on the specific cause of the condition, the severity, the patient’s health and immune status, and how quickly the condition is identified and treated. Patients with mild cases may recover fully within a few weeks or may have persistent or permanent complications. In general cases that are diagnosed and treated quickly have a good prognosis. However, as many as 15-25% of newborns and 15% of other patients with bacterial meningitis die, even when treated appropriately and rapidly. Up to 15-25% of those who survive may have neurological problems including hydrocephalus, cerebral palsy, deafness, blindness, seizures, and/or some degree of impaired thinking. Other complications may include limb amputation, renal problems and bone and joint problems usually from complications of septicaemia. Viral meningitis seems to carry a better prognosis. However, mortality following HSV infection of the central nervous system is 15%. HSV-1 and HSV-2 have the same risk of mortality but HSV-2 is more often associated with long-term complications such as cerebral palsy, mental retardation, seizures, microcephaly (an abnormally small head) and visual impairment. These complications may occur at any age, but newborns are at the highest risk. With regards to encephalitis, overall about 10% of cases are fatal.

Doctors start with a physical examination and a medical history. This examination may occur in the accident and emergency centre (A and E) as symptoms may suddenly appear and rapidly worsen over several hours to a couple of days. Of interest to the doctor are recent illnesses, exposure to animals, mosquitoes, or ticks, contact with other people who have become ill, recent travel and recent activities. The doctor will note the presence or absence of signs and symptoms frequently associated with meningitis and encephalitis. Neurological examinations may be performed to assess the status of the patient’s nervous system, their sensory and motor function, coordination, vision, hearing, strength and thinking.

Laboratory Tests
Laboratory tests are performed to detect, identify, evaluate, and monitor meningitis and encephalitis. These tests are performed in order to:

• Distinguish these infectious diseases from other conditions with similar symptoms
• Determine the cause – bacterial, viral, fungal, parasitic, or other as rapidly as possible to start and guide treatment
• Evaluate the patient’s general state of health, immune system status, current signs and symptoms, and current complications to guide symptom relief and to minimize inflammation and neurological or brain damage
• Where possible, determine the infection’s source; especially important when the causative agent may be a public health concern

Tests include:
Cerebrospinal fluid (CSF) analysis. This is an important test for encephalitis and meningitis. CSF analysis is a group of common tests that can be requested and performed on a sample of CSF fluid. CSF is collected using a procedure called a lumbar puncture or spinal tap.

Initial CSF tests—The initial basic set of CSF tests that are often performed with suspected infections of the central nervous system include:

• Physical characteristics. Normal CSF appears clear and colourless. The appearance of the sample of CSF is usually compared to a sample of water. In infections, the initial pressure of CSF during collection may be increased, and the sample may appear cloudy due to the presence of white blood cells (WBCs) or microorganisms.
• CSF protein. Only a small amount is normally present in CSF because proteins are large molecules and do not cross the blood/brain barrier easily. Increases in protein are commonly seen with meningitis, brain abscesses, and neurosyphilis and their presence in large amounts indicates infection.
• CSF glucose. Normal levels are about 2/3 the concentration of the blood glucose concentration. Glucose levels may decrease when cells that are not normally present use up (metabolise) the glucose. These may include bacteria or cells present due to inflammation (WBCs). Therefore a low CSF glucose may indicate the presence of infection.
• CSF total cell counts. WBCs may be increased with central nervous system (CNS) infections.
• CSF WBC differential. Small numbers of lymphocytes, monocytes (and in neonates, neutrophils) are normal in a sample of CSF. There may be:
  • an increase in neutrophils with a bacterial infection
  • an increase in lymphocytes with a viral infection
  • sometimes an increase in eosinophils with a parasitic infection
• CSF Gram stain for direct observation of bacteria
• CSF culture and sensitivity to identify the presence of bacteria, fungi, and viruses and to determine what medications would be effective in destroying them.

Additional or follow-up CSF tests—If any of the initial tests are abnormal, then additional infectious testing may be requested. This may include one or more of the following:

• Detection of viruses by PCR (polymerase chain reaction) – this involves the detection of viral genetic material (DNA, RNA) such as herpes and enteroviruses using a special biochemical method.
• CSF Cryptococcal antigen – to detect a specific fungal infection called Cryptococcus
• Other CSF antigen tests – depending on which organism(s) are suspected
• Specific CSF antibody tests – depending on which organism(s) are suspected

Less commonly requested CSF infectious diseases tests include:

• CSF AFB smear and culture (when tuberculosis is suspected) – positive with tuberculosis and with other mycobacteria
• CSF Molecular tests to detect Mycobacteria tuberculosis
• CSF syphilis testing (VDRL) – positive with neurosyphilis; a negative result however does not rule out the condition

Several other types of CSF testing may occasionally be requested to help distinguish between viral and bacterial meningitis:

• CSF lactic acid—may be used to distinguish between viral and bacterial meningitis. The level will usually be increased with bacterial and fungal meningitis while it will remain normal or only slightly elevated with viral meningitis.
• CSF lactate dehydrogenase (LDH) – is sometimes used to differentiate between bacterial and viral meningitis also.  The levels are usually a lot higher in bacterial meningitis.
• CSF C-reactive protein (CRP) is an acute phase reactant and is elevated with inflammation. It is markedly increased with bacterial meningitis. 

Laboratory tests on samples other than CSF—may be requested with or following CSF testing and may include:

• Blood glucose, protein, FBC (Full Blood Count) – to evaluate and to compare with CSF levels
• Tests for antibodies or antigens in the blood for a variety of viruses and bacteria e.g. syphilis, HIV. This can help identify if a patient is currently infected or has recently been infected with a microorganism that could potentially be the source of the meningitis or encephalitis.
• Blood cultures may be requested to detect and identify bacteria in the blood. This may be especially helpful if there is suspected septicaemia.
• Cultures of other parts of the body may be performed to detect the source of the infection that led to the meningitis or encephalitis e.g. urine.  A chest x-ray may also be performed for that same reason.
• U&Es, LFTs, CRP – tests that evaluate organ function.

Non-Laboratory Tests
Imaging tests may be performed to look for signs of brain inflammation or abnormalities but they may be normal with encephalitis. However, brain damage, tumours, bleeding, and abscesses may be detected. Tests may include:

• CT (Computed tomography) – this may also be used to diagnose raised intracranial pressure which is a contra-indication to a lumbar puncture.
• MRI (Magnetic Resonance Imaging)
• Ultrasound
• EEG (Electroencephalography) – to detect abnormal brain waves

There are vaccines available for Haemophilus influenzae type b, some types of Streptococcus pneumoniae, and Neisseria meningitides Type C. These can all cause meningitis and the vaccines are part of the routine immunisation schedule for children. Widespread vaccination of children has drastically reduced the incidence of Haemophilus influenzae type b as previously stated. The introduction of the meningitis type C vaccine has decreased the amount of meningitis caused by this strain. As a result, most cases of meningococcal meningitis in the UK currently are caused by Type B. Meningitis type C strains are more common in older children whereas type B seems to affect younger children particularly the under 5s. The UK’s first vaccine against Meningitis B (meningococcal group B) has recently been licensed for use in this country in ages 2 months and over. The new vaccine, called Bexser is not currently part of the UK children vaccination schedule. The Joint Committee on Vaccination and Immunisation (JCVI), who advise health ministers on vaccination, are currently considering which age groups should receive the vaccine if it is introduced into the routine schedule and guidance is expected in summer 2013. It is currently not available privately but is expected to be from the middle of 2013. It is not always possible to prevent encephalitis because it can be a rare complication of a relatively common infection. The NHS choices website advice however is that the most effective way to reduce your risk of encephalitis is to make sure you receive the MMR vaccine (for measles, mumps and rubella).

Other vaccines may be used for travellers going to meningitis-prone or encephalitis prone countries where arboviruses are more common. Vaccinations are available for Japanese encephalitis, tick-borne encephalitis and encephalitis caused by rabies. Arbovirus risk however can be minimised by limiting exposure to mosquitoes, limiting outdoor activities at night, wearing long sleeved clothing, using insect repellents, and eliminating freestanding water around the home.

Those with close contact with someone who has had meningococcal meningitis may be prescribed antibiotics for a few days to decrease their risk of developing an infection. Close contacts usually means household members, or intimate kissing contacts within the previous week. These people are offered a short course of antibiotics to prevent possible infection although their risk is low.

If group C meningococcus is the cause of the meningitis, then immunisation is also offered to close contacts. If there has been an outbreak of meningococcal infection antibiotics and/or immunisation may then be offered to a wider group of people e.g. students in the same class for example. It should be remembered however that simple measures such as hand washing will dramatically reduce your chances of catching the organisms that may be responsible for meningitis and encephalitis.