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How to identify and manage meningitis and encephalitis

Dr Nelly Ninis offers advice on making a diagnosis feared by doctors and patients

here are many travellers and refugees presenting in primary care so it is important to have some idea of pathogens they may bring with them. This review is largely confined to immunocompetent patients, although doctors need to be aware that infectious diseases commonly present in patients with congenital or acquired immune deficiency syndromes. These patients may not present with classic symptoms of disease and may have other stigmata of chronic immunodeficiency.

Within the central nervous system viruses have the potential to cause meningitis and encephalitis. Viral infections may also cause parainfection symptoms where the pathology seen in the brain is due to an immunological effect secondary to the presence of the virus rather than directly from the virus itself.

Viruses differ widely in their ability to cause infection in the central nervous system. Some, like rabies, exclusively cause central nervous system infection whereas others, like mumps, commonly cause central nervous system infection as part of the systemic infection but is usually benign.

 · Encephalitis The hallmark is altered level of consciousness, so-called 'clouding of consciousness', accompanied by fever and headache. Patients commonly are disorientated with behavioural and speech disturbances. There are diffuse or focal neurological signs present.

 · Meningitis In adults the classic triad of signs are headache, fever and nuchal rigidity. But in children and teenagers these signs are not reliable and clinicians must not discount meningitis in the absence of nuchal rigidity. Teenagers with meningitis may appear confused and combative and may appear to be intoxicated. Younger children will often not have nuchal rigidity and irritability may be the predominant feature.

Clinical features of encephalitis

Although physical examination of the patient does not usually result in an aetiological diagnosis, a few points are important including the presence of focal neurological signs.

In a non-epidemic setting herpes simplex virus-1 (HSV-1) is the most common cause of sporadic viral encephalitis with focal signs. HSV has a predilection for temporal lobe involvement leading to aphasia, anosmia and temporal lobe seizures.

Other viruses that normally cause diffuse encephalitic diseases can also occasionally localise to one part of the brain and mimic herpes simplex encephalitis.

One in three patients with HSV encephalitis is under 20 and half are over 50. In the absence of any treatment the mortality is more than 70 per cent with only 2.5 per cent surviving completely unscathed. The patient's age, level of consciousness and duration of encephalitis at presentation all influence outcome in those who receive treatment.

A poor outcome is associated with patients presenting deeply unconscious with a Glasgow coma score below six and illness lasting over four days before therapy is started. Outside the neonatal period most cases of herpes encephalitis are due to HSV-1. Half the patients will be having a primary herpes infection and two-thirds viral reactivation.

Unusual causes of central nervous system infections in the UK include polio and rabies but both infections should be considered in people recently arrived from abroad. Polio virus preferentially infects motor neurons leading to flaccid paralysis at presentation.

Rabies may be contracted after a bite or saliva exposure from infected dogs, bats or other wild animals like foxes. The incubation time varies depending on the distance of the site of the inoculums from the brain. Incubation varies from as little as five days to six months. There is a prodrome of fever, malaise, anxiety, pain and itching at the bite site.

This prodrome is followed by overt CNS findings that may be paralytic or encephalopathic. Coma and death follow, as no therapy is available. In Australia several deaths have been reported from infection caused by Australia bat lyssavirus.

Arthropod-borne encephalitis viruses

Viruses transmitted to humans through tick and mosquito bites are a major cause of encephalitis worldwide. These viruses are usually Togaviruses (eastern equine encephalitis), Flaviviruses (Japanese B encephalitis) and Bunyaviruses (La Crosse encephalitis).

Japanese B encephalitis ­ the most common of these ­ is found in China, south-east Asia, India and Pakistan, eastern Russia and Australia.

It is primarily a disease of children but adults become infected as it moves to a new area. After a few days of a prodrome, patients present with headache, vomiting, altered mental state and usually seizures. Other characteristic features include a coarse tremor, dystonia, rigidity and mask-like features.

The mortality rate is about 30 per cent with

50 per cent of survivors having neurological sequelae.

Clinical features of viral meningitis

Enteroviruses, particularly Coxsackie and echoviruses, are the most common cause of aseptic meningitis in the paediatric population. In the prevaccination era mumps virus was responsible for most cases of aseptic meningitis.

Although children are the primary victims of enteroviral meningitis the illness is not uncommon in the adult population. Often affected adults have close contact with children at home or in their jobs.

Enteroviruses are the most common cause of viral meningitis. Among the enteroviruses there are significant differences in clinical manifestations, especially those capable of causing epidemics such as enterovirus 71.

Usual clinical features include:

 · The start of the illness is usually acute

 · Most children have fever, which tends to last about five days

 · Older children tend to have headache

 · Photophobia is common

 · Meningeal signs are usually present in older children and in younger ones fever, irritability and lethargy predominate

 · Other manifestations of enteroviral infection also occur in children with viral meningitis, commonly pharyngitis, upper respiratory tract infection, myalgia, and diarrhoea.

Enteroviral infections can cause rashes that are shared with other more serious infections. Petechae and small areas of purpura can occur, vesicular rashes may also be seen which may alert the physician to the possibility of herpes simplex infection.

Examination of the vesicular fluid under electron microscopy and culture of the herpes virus is easily done and will help to differentiate pathogens.

Enteroviruses can cause a range of symptoms other than meningitis, including encephalitis, hand-foot-and-mouth disease, myocarditis, herpangina, rashes and diarrhoea. Symptoms may occur in combination.

There are few published reports describing the presentation and outcome of enterovirus meningitis in large numbers of adults. In one French study of 30 adults with proven enteroviral meningitis only 59 per cent of the patients had fever, headache and neck stiffness. Headache was the most common symptom.

Although the clinical course of most enteroviral infections is benign and self-limiting, there have been a few notable exceptions.

Enterovirus 71 has been associated with epidemics of severe disease. These have occurred in eastern Europe and most recently in Taiwan in 1998. In the Taiwanese outbreak the mortality rate was 14 per cent.

Investigation

It is important that all patients with any signs of central nervous system infection are referred urgently. Taking a detailed travel history from parent and relative is important early on as it may point to the diagnosis and allow appropriate safety precautions to be taken if rabies is suspected. Highlighting the presence of focal signs is obviously important.

Investigation of patients with signs of intracranial infection should be tailored to the patients' physical signs and presumptive diagnosis.

 · Lumbar puncture and cerebrospinal fluid examination This is essential unless contraindicated by the presence of raised intracranial pressure. In both viral meningitis and encephalitis there is usually an increase in the CSF protein level and the number of white cells, which tend to be mononuclear cells. Glucose level should be normal in viral meningitis. Gram stain of the fluid and culture is mandatory if there are >5wcc/mm3. A small percentage of patients (<5 per="" cent)="" may="" have="" normal="" csf="" at="" the="" start="" of="" the="" illness.="" specific="" polymerase="" chain="" reaction="" (pcr)="" tests="" for="" herpes="" viruses="" and="" enteroviruses="" are="" available:="" igm="" for="" japanese="" b="" encephalitis="" should="" be="" done="" if="" this="" is="" suspected="" and="" pcr="" tests="" for="" other="" arboviruses="" are="">

 · EEG EEG may show general features of encephalopathy. Herpes simplex encephalitis has characteristic features of periodic high voltage spike-wave activity emanating from the temporal regions and slow-wave complexes at two-three second intervals.

 · Imaging Patients with classic features of meningitis without complications do not necessarily need scanning. Diagnosis of raised intracranial pressure is clinically made and lumbar puncture delayed accordingly. Patients with focal signs and deeply depressed conscious level are usually scanned.

MRI scanning will show features of focal infection but may be normal early on in the infection and may have to be repeated. Widespread demeylination may be present and may indicate presence of

post-infectious encephalomyelitis.

Treatment

 · For patients with signs of encephalitis, full treatment consists of high-dose intravenous aciclovir for 21 days. Shorter courses than this have been associated with relapse if the encephalitis is due to HSV.

 · Patients presenting with signs of meningitis are treated as for bacterial meningitis with appropriate antibiotics (often third-generation cephalosporins, although benzylpenicillin should be used in primary care). TB treatment should be considered early if the CSF culture is negative and clinical features are suggestive of possible TB. This is most common in children and often follows a viral respiratory infection. Treatment is steroids and prognosis is good.

As well as meningitis and encephalitis, viruses may also cause an immunological effect in the brain ~

How to identify and manage meningitis and encephalitis

Aetiological clues in the history

 · Season Late summer or early autumn usually coincides with the peak of enteroviral infections in temperate climates, although sporadic cases occur throughout the year

 · Travel A good travel history is essential in all patients with signs of central nervous system infection as they may be infected with a pathogen foreign to the UK

 · Recreational activities Caving may lead to contact with bats that carry rabies, hiking may expose a patient to tick or mosquito bites

 · Animal contacts Especially dogs (potentially carrying rabies)

Although children are primary victims of enteroviral meningitis the illness is not uncommon in adults~

How to identify and manage meningitis and encephalitis

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