Huntington's chorea

THE PURPOSE of this preliminary report is to demonstrate that the method of infrared spectrophotometric analysis (IRS), hitherto not employed in studies of human brain, is capable of distinguishing between such a relatively specific hereditary atrophic disease as Huntington’s chorea from nonhereditary degenerative disease. That tissue from brains of patients having different neuropathological characteristics (as well as tissues from different anatomical sites having different morphology and function) might be differentiated was suggested by a report (KABLER, IDDLE, and KANNER, 1956) on studies of 142 strains of coliform and related bacteria which showed differentiation of every species and serologic group by the IRS method. Brains were obtained at autopsy from eighteen patients, four of whom carried a diagnosis of Huntington’s chorea (chronic, progressive, hereditary chorea), verified by presence of the disease in at feast one previous generation and typical symptoms. Cause of death was usually bronchopneumonia, or complications from the disabilities caused by the illness. There were three males and one female, with ages ranging from 42 to 59 at death, and elapsed times from death to autopsy from 3 to 17 hr. The fourteen patients without hereditary brain disease included seven males and seven females, with ages ranging from 58 to 88, usually carrying a diagnosis of psychosis with cerebral arteriosclerosis or psychosis with senility, dying of a variety of neoplastic, degenerative, or infectious disorders, with elapsed times from death to autopsy of 4-26 hr. Brain samples (10-20 mg) were dissected from the following sites: (a) 15-20 mm lateral to the medial surface of the right hemisphere as thin cortical shavings for (1) superior frontal gyrus, (2) precentral gyrus, and (3) postcentral gyrus; (b) most anterior midline pole of the genu of the corpus callosum; and (c) the centers (excluding ependyma and internal capsular tissue) of the heads of the caudate and putamen as seen on the frontal surface of brains transected at the level of the anterior margin of the decussation of the optic nerve. All samples were inserted in identified aluminium vials and immediately frozen with liquid nitrogen and maintained in the frozen state until freeze-dried in a Vir-Tis freeze-drying apparatus. Subsequently, the samples were stored over calcium chloride in a sealed desiccator until compounding with potassium bromide. A suitable amount of sample (2.000 to 3.000 mg) was weighed on a Federal-Precision 0-5 mg balance, and incorporated in 200 mg of IR grade KBr by grinding in a mortar. The KBr pellet was pressed at 22,000 Ib. /in. % for 5 min. The spectra were obtained on the Perkin-Elmer 337 IR spectrophotometer with the 3 min scan, normal slit. Eleven peaks were chosen for study. The total absorbance at each peak was determined by the base line method. This value was divided by the weight in milligrams per sample to obtain absorbance per milligram of sample. All subsequent calculations were based upon this value. Significance of difference was determined by the t test. The substances causing absorbance at the peaks studied have not been determined, but this problem is presently under investigation. In this study six tissues were subjected to IRS: (1) caudate, (2) putamen, (3) superior frontal gyrus, (4) precentral gyrus, (5) postcentral gyrus, and (6) corpus callosum. The data of this study (Table 1) indicate that there are specific chemical differences between the two groups of tissues reported, either in kind or quantity. Brain tissue samples from patients with Huntington’s disease (Hd) differed from those from patients with non-hereditary brain disease in five of the eleven spectral peaks studied from caudate, in ten of the eleven peaks studied from putamen, in two peaks for tissue from superior frontal gyrus, and in one peak from corpus callosum. Identical peak occurrence in infrared spectra re resents identical molecular structure. In multicomponent samples, each component makes its in B ividual contribution to the total spectrum. Any change in kind or quantity of the individual compounds in a multicomponent system will be reflected in change in the infrared spectra. The spectra of the tissues studied showed such differences.