Histological and chemical findings in Krabbe's leucodystrophy.

The familial disease of the cerebral white matter named after Krabbe (1916) may be distinguished histologically from other leucoencephalopathies of early life by the presence of conspicuous nests of macrophage cells, some of large size with several peripherally placed nuclei, lying closely packed around the smaller vessels of the cerebral white matter. The large multinucleated cells were designated 'globoid cells' by Collier and Greenfield (1924), and Greenfield (1958) later gave the name 'epithelioid' to smaller mononuclear cells which also help to form the perivascular packets. Both types of cell contain a substance having the histochemical properties of a glycolipid bound to protein (Diezel, 1955; Stammler, 1956). Since mononuclear, or sometimes multinuclear, cells containing complex lipid material may be present in other types of diffuse sclerosis (Ferraro, 1927; Seitelberger, 1960), it is necessary to stress in the definition of Krabbe's disease this relationship of the cell packets to the smaller vessels. If this criterion is applied, there are some 25 recorded cases of this disorder (Hallervorden, 1957), all of which concerned children dying before the age of 7 years. There are also two, more doubtful, sporadic cases which have been described in adults (Verhaart, 1931; Guillain, Bertrand, and *Gruner, 1941). This list includes the earliest case on record, that of Bullard and Southard (1906), who described typical neuropathological findings in a boy dying at the age of 61 years after an illness lasting one year. There has been much speculation as to the origin and function of the globoid cells, whether they are formed by microglia engaged in engulfing and transporting products of myelin breakdown to the vessels, or whether they are derived from the vascular adventitia and, if so, whether their abnormal lipid content is a phenomenon of primary storage, as in a lipidosis. The recent observations of Stammler (1956) strongly suggest that the perivascular globoid and mononuclear cells are both adventitial derivatives and our cases throw further light on this important feature. The histological observations on these cases have been supplemented by chemical analysis of the cerebral cortex and white matter, using a method by which neutral or true cerebroside may be separated from other glycolipids. We have found this to be present in relatively normal amount despite the severe degeneration of the white matter and a substantial loss of other myelin lipids.