Matching of the postmortem hypothalamus from patients and controls

The quality of postmortem hypothalamus research depends strongly on a thorough clinical investigation and documentation of the patient’s disorder and therapies. In addition, a systematic and professional neuropathological investigation of the entire brain of both the cases and the controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of the clinical neurological diagnoses, despite being made in first rate clinics, have to be revised or require extra diagnoses after a complete and thorough neuropathologic review by the NBB. The neuropathology examination may reveal for instance that the elderly “controls” already have preclinical neurodegenerative alterations. In postmortem studies, the patient and control groups must be matched for as many as possible of the known confounding factors. This is necessary to make the groups as similar as possible, except for the topic being investigated. Confounding factors are present (i) before, (ii) during, and (iii) after death. They are, respectively: (i) genetic background, systemic diseases, duration and gravity of illness, medicines and addictive compounds used, age, sex, gender identity, sexual orientation, clock- and seasonal time of death, and lateralization; (ii) agonal state, stress of dying; and (iii) postmortem delay, freezing procedures, fixation, and storage time. Agonal state is generally estimated by measuring the pH of the brain. However, there are disorders in which pH is lower as a part of the disease process. Because of the large number of potentially confounding factors that differ according to, for instance, brain area and disease, a brain bank should have a large number of controls at its disposal for appropriate matching. If matching fails for some confounders, the influence of the confounders may be determined by statistical methods, such as analysis of variance or the regression models.