Distinguishing Encephalitis from Encephalopathy


Encephalitis may be defined as infection or inflammation of the brain substance, resulting typically in disturbed sensorium and perhaps seizures or focal neurological deficits and sometimes pyrexia. Encephalopathy in the other hand represents disturbed sensorium not due to an infective or inflammatory cerebral process and its causes range from toxins and drugs to metabolic upset, non cerebral sepsis, cerebral hypoperfusion and post-ictal states.

Distinguishing the two is important because considerable morbidity and mortality is associated with delayed treatment with appropriate antiviral, antibiotic or immune therapy for encephalitis and with delayed treatment of the various causes of other causes of encephalopathy.

The paper presented, “To what extent can clinical characteristics be used to distinguish encephalitis from encephalopathy of other causes? Results from a prospective observational study” by Else Quist-Paulsen et al., attempts to use clinical and rapidly available investigatory findings to distinguish the two conditions by a prospective observational study on 136 patients.

They identified candidate patients on the basis they had a lumbar puncture, and then excluded those with no evidence of encephalopathy. Their criteria for encephalitis were:

  • Pyrexia
  • Encephalopathy > 24 hours with no other cause identified and 2 of:
  • CSF WCC >=5 x 106/l
  • New onset seizures
  • New onset focal neurological findings
  • CT/MRI consistent with encephalitis
  • EEG consistent with encephalitis

The gold standard by which to gauge their test would surely be a definitive diagnosis but, as is commonly the case in clinically suspected encephalitis, such a diagnosis was only made in 10 of 19 patients. In some of the patients with non-encephalitis encephalopathy, the diagnosis was also vague, e.g. “aseptic meningitis” (which could be encephalitis), “epilepsy” (which could be autoimmune encephalitis), “headache/migraine”, “unspecified disorientation or coma”.

Subsequent analysis of specific features in the two groups then becomes somewhat difficult because the criteria themselves become the gold standard and because some specific features were in themselves their criteria. Interestingly, systemic features of infection such as raised blood white cells or CRP, argued against encephalitis because general sepsis was a common cause of encephalopathy. Nausea and personality change were more common in their encephalitis group.

They used ROC curves to look at the predictive value of these specific features and their combinations, but these were again based against their “testing variable”, their criteria, not on some objective gold standard. It would have been better to look at them only in the 10 diagnosed cases rather than all 19, but then the total number of cases would be even lower.

The diversity of diagnosis of their cases was interesting, especially that Lyme disease and TB were as common as VZV and more common than HSV. Only one of their cases had NMDA receptor antibodies, but we do not know that all the patients had this test and a full battery of other autoimmune antibody tests. Many might have been put in the encephalopathy with seizures category. Since encephalitis can be associated with meningism, some “aseptic meningitis” patients might have been viral but with negative testing, or even autoimmune with a migrainous headache and stiff neck.

The group felt that the study was very worthwhile but a more clear guide as to which cases of encephalitis warranted antimicrobial therapy  or immune therapy would be the clear goal. This would require clarity on the gold standard diagnosis and many more patients.

The Journal Club discussion on which this post is based was presented by Dr Aram Aslanyan, Specialist Registrar in Neurology at Queens Hospital, Romford, Essex.


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