It is really fascinating that even after a person has been declared legally dead the cells of his/her brain are still capable of reacting to environmental stimuli. In effect, as early as a few minutes after death enzymes that had been closely guarded in membrane bound sacs (called vacuoles) break away and digest many tissue components in a process called autolysis. This process occurs quite rapidly in the brain because it is so rich in many enzymes. A few hours later bacteria within the respiratory and gastrointestinal track join the process of decomposition in what is called putrefaction. In about 3 days putrefaction will change the custard like consistency of the brain into a grey reddish liquid.

The purpose of putting a brain into a fixative is to preserve the state of the tissue in as close a life-like state as possible. The fixative accomplishes this by stabilizing proteins in the tissue and arresting bacterial decomposition. Fixation has to be done early enough as it is hardly adequate to fixate autolyzed tissue which is mostly liquid.

There are many variables that affect the process of autolysis and putrefaction. It is said, for example, that a high environmental temperature may increase the rate of decomposition. Also, many characteristics of the diseased person may play a role including obesity, congestive heart failure, and state of hydration.

Many of the factors described in the previous paragraphs can make fresh brain weights an unreliable measure of brain volume during the life of the patient. Furthermore, put a fresh brain into a fixative with a low concentration of salts and it will swell tremendously. This increase will be more noticeable in children as compared to adults. Unfortunately neither gross nor microscopic examination helps in distinguishing how much of the brain weight is real vs. how much has been gained as artifact.

Most neuropathologists would not consider as research performing brain weight comparisons among different series of cases. Given all the limitations previously mentioned it is no surprise that many or the reported studies on brain weight relate to psychiatric conditions and are usually performed by researchers lacking expertise in neuropathology. Furthermore, in most available reports within the autism literature: 1) it is hard to define whether the brain weights were collected fresh or after fixation, and 2) almost none define the state of the patient around the time of death. These are critical variables by which to judge the reliability of brain weight findings.

Bauman and Kemper have great expertise in the fields of Neurology and Neuropathology. Their efforts in regards to brain weights centered on a series of 12 autistic children (5-13 years) and 8 adults (18-54 years) (Bauman and Kemper, 1994). The investigators concluded that their data was consistent with earlier studies suggestive of an early acceleration in brain growth followed by normalization with aging. The series included 3 outliers and was not analyzed taking this into account.

Bailey et al. (1993) reported heavier weights in 3 out of their 4 autistic subjects (4-27 years). The authors were able to increase their series with 2 additional cases (Bailey et al., 1998). However, description of their brains suggests that half of the sample could have postmortem brain swelling and one specimen in particular showed obvious signs of putrefaction. None of these specimens should have been included in a neuropathological study.

Courchesne et al. (1999) added to the literature by reporting on 21 cases (5 new cases and 16 taken from the literature) and compared them to 6 normative series. They concluded that brain weights of autistic individuals were usually within the normal range with rare cases of megalencephaly. The series was pursued in a later metanalysis of 55 specimens (Courchesne et al., 1999; Redcay and Courchesne, 2005). The researchers concluded this time that there was a divergence of brain weights early in life that normalized with aging.

The series are few and the number of cases within each one is extremely small. Given all of the limitations previously quoted and the lack of pertinent information provided by the authors the significance of the findings is hard to judge. What may be of even greater importance is that on many occasions these specimens, with artefactual changes, have been used in order to perform “quantitative” cell counts and densities. Ballooning of the brain due to postmortem swelling will clearly bias any such attempts at quantitation.

References

Bailey, A., Luthert, P., Bolton, P., Le Couteur, A., Rutter, M., & Harding, B. (1993). Autism and megalencephaly. The Lancet, 341, 1225–1226.

Bailey, A., Luthert, P., Dean, A., Harding, B., Janota, I., Montgomery, M., Rutter, M., & Lantos, P. (1998). A clinicopathological study of autism. Brain, 121, 889–905.

Bauman, M. L., & Kemper, T. L. (1994). Neuroanatomical observations of the brain in autism. In M. L. Bauman & T. L. Kemper (Eds.), The neurobiology of autism (pp. 119–145). Baltimore: Johns Hopkins University Press.

Courchesne, E., Müller, R. A., & Saitoh, O. (1999). Brain weight in autism: Normal in the majority of cases, megalencephalic in rare cases. Neurology, 52, 1057–1059.

Redcay, E., & Courchesne, E. (2005). When is the brain enlarged in autism? A metaanalysis of all brain size reports. Biological Psychiatry, 58, 1–9.