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Encephalitis – from laboratory bench to bedside
Mortality rates following Encephalitis are high; and even when people survive they may be left with devastating disability that can profoundly affect both their own lives and those of their loved ones.
Encephalitis, in common with many other neurological conditions has traditionally been a diagnosis of exclusion. That is to say physicians have not had a single test to confirm the diagnosis; but instead have relied upon their experience, clinical acumen and exclusion of other possible diagnoses before reaching the diagnosis of encephalitis. In other fields of medicine, such as in genetic conditions, science has provided detailed explanations as to the cause of disease resulting in simple, reliable diagnostic tests. However, our understanding of how, why and which infections and auto-immune responses cause inflammation of the brain is comparatively poorly understood.
We need a better understanding of the pathophysiology of encephalitis (i.e. how the infection or auto-immune responses causes the disease). We need better clinical predictors of encephalitis so that treatment can be started early. We also need to be able to identify the causes of the many unknown forms of Encephalitis which still present today. Only with large prospective clinical trials will such data be produced.
To begin to unravel the complexities of a diverse condition such as Encephalitis, one approach is to attempt to identify the culprit organisms responsible. This task has been aided by the revolution biological science has undergone over the last twenty years. Technical advances in the new science of “molecular biology” allow the study of the biochemistry and genetics of individual cells. Such techniques are now becoming reliable enough to use routinely in the pathology lab and offer the advantage of being many times more sensitive than older technology. An example of a new technique is the polymerase chain reaction (PCR). We are all familiar with criminals being convicted on the evidence of their “genetic fingerprint” being found in microscopic amounts at crime scenes. PCR is one of the techniques used by forensic scientists to identify the unique “genetic fingerprint”. Similarly, bugs such as viruses leave their “genetic fingerprints” at the site of infection. In encephalitis, examination of the fluid that bathes and nourishes the brain (cerebrospinal fluid) at lumbar puncture offers the chance to spot the fingerprint and identify the infection.
However, one of the challenges of introducing new diagnostic tests is to understand what the results mean in the context of the patient’s condition. Our ability to find the fingerprints of bugs suggests that they may be involved in many more disease processes than previously thought. The work of our collaboration aims to capitalise upon these techniques to identify the causes of encephalitis rapidly and reliably. In addition, we aim to increase our knowledge how test results correlate with what the physician sees at the bedside. We hope that such endeavours will allow greater understanding of the causes of encephalitis and direction of appropriate treatments.
The diagnosis of CNS infections has been revolutionized by the use of rapid diagnostic techniques, including the polymerase chain reaction (PCR) and highly sensitive and specific IgM capture ELISAs. In addition, treatment of previously untreatable viral encephalitides is becoming a reality with the advent of new antiviral drugs, and the wider application for older drugs. These drugs are effective in the laboratory, and in animal models. Some have even been tried in a few humans with encephalitis, but they need to be assessed properly in clinical trials.
Dr Nicholas Davies Consultant Neurologist Chelsea and Westminster Hospital, London.