7oumnal ofNeurology, Neurosurgery, and Psychiatry 1993;56:1243-1258 1 243 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.12.1243 on 1 December 1993. Downloaded from NEUROLOGICAL EMERGENCY Management of cerebral infection Milne Anderson Acute meningitis is the most common of the echo, and less commonly by herpes simplex cerebral infection syndromes. Epidemiology, type 1, varicella zoster, mumps, lymphocytic pathogenesis, and evolution are complex, and choriomeningitis, and HIV. vary with geography and with age. The clinical onset is usually rapid over Presentation occurs within hours, or at most hours, with pyrexia, malaise, headache, neck a few days, of the onset of symptoms which, stiffness, photophobia, lethargy, myalgia and with the signs, are characteristic: headache, irritability. Most cases do not progress fur- fever, photophobia, irritability, neck stiffness, ther, and the subject can be roused easily and and changed mental state. The causal agent is remains coherent. If the conscious level either a virus or a bacterium. Fungi and para- reduces, or focal signs or seizures occur, sites cause acute meningitis only in excep- encephalitis is implied. Resolution begins tional circumstances. Viral meningitis is a within a few days and is complete within two much more benign illness than the bacterial weeks in most. A few will have persistent form. malaise and myalgia for some weeks. The pathogen is seldom identified clinically- parotitis and orchitis may point to mumps, Viral meningitis arthralgia and lymphadenopathy to HIV, The term "acute aseptic meningitis" was myalgia and myocarditis to coxsackie, and coined by Wallgren in 19251 to describe acute rashes to enteroviruses. The illness is not as meningeal irritation, benign and self-limiting, severe and prolonged as bacterial meningitis, with complete recovery and sterile pleocytic and the signs are not so marked. CSF. It has since become evident that at least 70% of such cases are caused by viruses. DIFFERENTIAL DIAGNOSIS CNS viral infections are complications of sys- Conditions from which viral meningitis must temic viral infections, and the virus gains be differentiated are the early stages of bacte- access to the brain by the bloodstream or, less rial meningitis, some cases of subarachnoid commonly, by travelling up peripheral haemorrhage and other causes of aseptic http://jnnp.bmj.com/ nerves.2 Viral meningitis is the result of meningitis, partially treated bacterial menin- haematogenous infection and, to enter the gitis, meningitis caused by fastidious bacteria, CNS, the virus must cross the endothelial cell fungi and parasites which do not readily grow junctions of the blood-brain barrier, the abil- in routine culture, parameningeal infection, ity to do this being dependent upon surface inflammation or neoplasia, and collagen dis- adhesion molecules on the cells, surface ease. To confirm the diagnosis, CSF exami- charges and cellular receptors of the virus, nation is mandatory, but not before and the property of entering infected cells.' dangerously raised intracranial pressure on October 2, 2021 by guest. Protected copyright. Certain viruses preferentially infect the (ICP) or a space-occupying lesion has been meninges, choroid plexus, and ependyma excluded by appropriate imaging. CSF pres- rather than cerebral parenchyma, causing sure is normal or slightly raised, and the fluid meningitis; others infect neurons and glia to is clear to the naked eye. Cell counts are in cause encephalitis. There is, however, consid- the range of up to 500-1000 white cells, erable overlap, and some viruses may cause mainly lymphocytes, although in some, poly- meningoencephalitis, incorporating signs of morphs may predominate. In such cases it is both. prudent to re-examine CSF 12-24 hours later Most cases of viral meningitis occur in chil- to identify a lymphocytosis and exclude a dren and young adults worldwide. Infections bacterial cause.7 CSF protein may be slightly occur throughout the year, with a preponder- raised, glucose is normal or only a little ance in summer and autumn in temperate cli- reduced. Numerous laboratory tests have Midland Centre for mates. been applied to CSF with the claim that they Neurosurgery and The annual reported incidence varies Neurology, Holly from 1 1 to 27 cases per 100 000,4 5 and over differentiate a bacterial from a viral aetiology, Lane, Smethwick, 7000 cases are reported annually in the but none is sufficiently discriminating to be Warley, West United States6: the actual number of infec- useful. These include lactate, lysozyme, C- Midlands B67 7JX Milne Anderson tions is almost certainly several multiples reactive protein, and creatine kinase estima- Correspondence to: higher, because of under-reporting. Over half tions. A similar lack of specificity applies to Dr Anderson are caused by enteroviruses-coxsackie-B or the occasional abnormalities that may be seen 1244 Anderson in blood counts, blood biochemistry, and the mumps? Has there been travel to or from an J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.12.1243 on 1 December 1993. Downloaded from EEG. area that harbours known vectors? Is there In most cases it is not necessary to estab- past or present evidence of an animal or lish an exact aetiology for treatment purposes, insect bite? What is the season of the year? as the disease is benign and self-limiting and, Diagnostic tests may help, yet in perhaps as provided other similar treatable diseases have many as a third of all cases, no specific aetiol- been excluded, symptomatic treatment with ogy can be established. analgesics and anti-emetics is all that is Viral encephalitis is not rare, and it occurs required. Antibiotics should not be given. globally. In the UK and Europe, most cases To establish the aetiology, the virus may be are sporadic accompaniments of common isolated from CSF or by serological studies of infections such as mumps, measles, and her- acute and convalescent serum samples, iden- pes simplex. In the United States, sporadic tification of IgM antibody or viral antigen in and epidemic forms are caused by the CSF. The application of recently developed arboviruses (arthropod-borne), and Japanese immunological and DNA probe amplification B encephalitis causes most epidemic infec- techniques, including polymerase chain reac- tions elsewhere. As many as 20 000 cases per tion (PCR), to detect viral antigen, is promis- annum may occur in the United States." ing.8 In the UK, their use at present is Patients who develop viral encephalitis dictated more by local availability than by often have a prodrome lasting several days, clinical need. which may include myalgia, fever, malaise, mild upper respiratory infection, rash, or parotitis. The development of headache, Viral encephalitis mental change, and drowsiness implies Acute viral encephalitis is due to direct inva- encephalitis, which is usually associated with sion of brain parenchyma, and the clinical meningitic features. As the disease progresses, manifestations are caused by cell dysfunction disorientation and disturbance of behaviour from this invasion and associated inflam- and speech worsen, and drowsiness becomes matory change. At the bedside this may coma. Epileptic seizures are common, and be indistinguishable from post-infectious focal signs may appear appropriate to the area encephalitis, the pathology of which is perive- of the brain taking the brunt of the infec- nous demyelination thought to be caused by tion-hallucinations and memory upset from allergic or immune reactions triggered after a the temporal lobes, hemiparesis, spasticity, latent period by viral infection.9 10 Viruses are sensory loss and speech upset, and cerebellar far and away the commonest cause of deficits. There may also be signs of raised encephalitis globally, but in certain locations intracranial pressure. The very young, the and seasons other organisms such as malaria very old, and those with compromised and other protozoans, rickettsiae and fungi immune systems often have more severe dis- may induce an encephalitic syndrome. ease. Signs should be sought in other organ As with meningitis, so with encephalitis, systems, which may point to a particular the virus reaches the brain by the blood- virus. Some forms of encephalitis have spe- stream. Entry may be through the skin fol- cific features which are briefly discussed later. lowing an insect bite, as with arbovirus infection, or via the respiratory or gastroin- testinal route. Local replication ensues, the DIFFERENTIAL DIAGNOSIS inoculum spills into blood and so to the retic- The list of other diseases that may cause a http://jnnp.bmj.com/ uloendothelial system whence, following fur- similar clinical picture is large, and includes ther replication, viraemia increases, and all forms of bacterial meningitis, malaria and spread takes place to other sites including the other protozoal and fungal infestations, CNS. Modification of this process by host intracranial suppuration, septicaemia and immune responses may occur, and if these endocarditis, metastatic disease and col- are compromised, disease progression may be lagenoses, and drug abuse. fulminant. Most cases of encephalitis are Faced with a patient with rapid onset of on October 2, 2021 by guest. Protected copyright. caused in this way. The virus may also ascend pyrexia and stupor or coma, the above poten- neurons centripetally to lodge in brain cells, tially remediable conditions need to be as with herpes simplex encephalitis and excluded quickly.