Differential diagnosis

The list of diseases that may cause a similar clinical picture is large and includes all forms of bacterial meningitis, malaria and other protozoal and fungal infections, intracranial suppuration, septicaemia and endocarditis, metastatic disease, collagen/vascular disease, drug abuse, and metabolic encephalopathies.

Faced with a patient with rapid onset of pyrexia and stupor or coma, the above potentially remediable conditions need to be excluded quickly. Blood counts and biochemical tests are not diagnostic but may be abnormal as a result of inadequate hydration or inappropriate secretion of antidiuretic hormone. If indicated, blood films should be examined for malaria parasites and blood cultures should be set up.

As these results are awaited, the brain should be imaged to determine if there is a space occupying lesion, cerebral oedema, or focal areas of necrosis, such as might occur in the temporal lobes with herpes simplex encephalitis (HSE). Some of the abnormalities are subtle and it is necessary to interpret the scans with close attention to their timing in the evolution of the disease. In the first two or three days there may be no obvious abnormality and repeat scanning may be necessary. MRI scanning is preferable to CT because it may reveal abnormalities missed by CT scanning and cerebral oedema and white matter abnormalities are easier to see.14 Unfortunately MRI scanning is not always available for emergencies. Furthermore, it is not always appropriate for a seriously ill patient, as the acquisition time for images is quite long, and any movement degrades the images. In patients with encephalitis the EEG is abnormal, most often showing non-specific diffuse slow wave activity, perhaps with seizure activity. Temporal lobe focal abnormality with high voltage spike and slow wave complexes is highly suggestive of HSE.

The CSF should be examined as soon as possible when deemed safe; unfortunately cranial scanning does not convey an accurate picture of intracranial pressure and judgement of the potential safety of lumbar puncture requires experience and not a little luck. The decision to examine CSF in such circumstances should not be taken by a junior doctor. The CSF is often under pressure and there is usually a leucocytosis, with between 10 and several thousand white cells per mm3. These are principally lymphocytes but polymorphs may predominate in the early stages. Red cells may be found if there is a necrotising component, as in HSE. The glucose content is normal, protein is raised, and organisms are not seen. In 3-5% of patients with severe viral infections of the CNS the CSF may be completely normal.

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