Abstract
Diagnosing encephalitis is often difficult with a definitive diagnosis being reached at best in only 40% of cases. This clinical condition is associated with a high morbidity and mortality. A brain biopsy is the gold standard for the diagnosis of this disease. However, this procedure is rarely done, resulting in the cause of death being largely speculative. We propose a simple procedure for postmortem brain biopsy through the transnasal transcribriform route that will possibly be more acceptable to clinicians and relatives alike due to lack of external disfigurement, relative ease of the procedure and economy of time and manpower. This could also prove to be of immense benefit in an epidemic of encephalitis, especially in remote areas.
Introduction
Encephalitis outbreaks are common, especially in developing countries. 1 Diagnosing encephalitis is often difficult 2 and involves the correlation of the clinical picture with cerebrospinal fluid (CSF) findings including polymerase chain reaction (PCR), 3 serological tests, imaging studies of the brain, 4 electroencephalogram (EEG) 5 and an open brain biopsy. 6 The serological tests used require paired samples, which are often difficult to obtain and have relatively poor sensitivity and specificity.
A definitive diagnosis using these methods is reached, at best, in only 40% of cases. 6 Hence, in most clinical situations only a probable diagnosis is made, based on the clinical picture which includes consideration of seasonal variations, geography, sexual history and a history of animal contact.
Given the above, there is an urgent need for user-friendly novel diagnostic approaches. The gold standard for the diagnosis of encephalitis is a brain biopsy. This refers to an open brain biopsy and is not commonly done, as it requires advanced facilities, neurosurgeons and trained neuropathologists, microbiologists and virologists. 1,6 Limited access to good health facilities, as well as the presence of social prejudices, means that in developing countries an antemortem brain biopsy is often not possible. This does not detract from the importance of making an accurate diagnosis, especially during an epidemic 7 as preventive measures, including vaccines and appropriate treatment measures, can then be put in place. There are very few reports of postmortem transcribriform brain biopsies using a Vim-Silverman needle which were performed more than 20 years ago. 8,9
We propose a modified brain biopsy procedure using a trucut needle – which is simpler to use – that could lead to a more accurate diagnosis of both epidemic and sporadic cases of encephalitis.
This test is done postmortem, after informed consent from the relatives. The needle used is a trucut needle, similar to that used for biopsies of other tissues such as the pleura. 10 The deceased is positioned supine. The trucut needle is advanced through either nostril; the cribriform plate is then punctured with minimum resistance. At this point the needle is within the brain parenchyma. It then advanced by 0.5–1.0 cm and the brain tissue is entered. As this is a postmortem test the needle can be advanced as deep as required. The biopsy is performed, a core of brain tissue is obtained (usually about 1–2 cm long) and the needle is withdrawn. The procedure can be repeated at different angles to ensure a better diagnostic yield. After the procedure, the nostril is packed well to a prevent CSF leak.
The tissue obtained is put into both a sterile saline, for culture and other microbiological testing, and into formalin, for pathological evaluation. Ideally, the biopsy should ideally be performed without too much delay to avoid any autolytic changes.
Discussion
The advantages of this procedure are the relative ease of acquiring samples and the lack of external disfigurement to the patient, which makes the procedure more socially acceptable. Moreover, the biopsy can be done in any centre, however remote, and transported to laboratories where they can be processed and analysed. The entire procedure can be done in less than a minute and requires very little expertise. This procedure may also be used in the postmortem diagnosis of other frontal or temporal lobe diseases where a brain biopsy is required and where an open biopsy is not possible for some reason.
However, there are potential problems with this procedure. If the disease process is focal, and involves primarily the parietal and occipital lobes, it will not be feasible to obtain a representative sample by this route. Relatives who find an open brain biopsy unacceptable may have similar reservations regarding this procedure. Some contamination of the biopsy specimen with nasal mucosal tissue from the superior surface of the nasal cavity may occur. Also, delay in the tissue sample reaching the reference laboratories could result in inconclusive microbiological and virological data. We have attempted this procedure on a few patients who have died in the medical intensive care unit from an unknown illness, with encephalitis as one of the possible diagnoses. We were successful in all the cases in obtaining a good core of cerebral cortex and white matter. However, none of these cases showed evidence of encephalitis.
We believe that any clinician faced with a patient who has expired with a possible diagnosis of encephalitis, where an open brain biopsy was not performed, can attempt this procedure. It requires informed consent, a sterile trucut needle, sterile saline, formalin and the ability to transport the tissue obtained reasonably quickly to a laboratory.
Conclusion
We have drawn attention to this procedure as it promises to be useful when performed on patients with suspected encephalitis, either during an epidemic or for sporadic cases. Further studies, however, are required in order to assess the usefulness of this procedure. We hope health officials and epidemiologists will consider evaluating the procedure during the next epidemic or the next case of suspected encephalitis.