DISSEMINATED NEOCORTICAL AND SUBCORTICAL ENCEPHALOPATHY (DNSE) WITH WIDESPREAD ACTIVATION OF BRAIN MACROPHAGES - A NEW DEMENTIA DISORDER - AUTOPSY REPORTS OF 2 POSTMENOPAUSAL WOMEN FROM FAMILIES WITH MITOCHONDRIAL-DNA MUTATIONS

In this study we present 2 postmenopausal women who showed clinical sy mptoms that resembled those of a rather well-defined group of vascular dementia disorders, termed subcortical dementia (Binswanger disease, CADASIL). Patient 1 exhibited mitochondrial DNA (mtDNA) variants in th e ND5 gene at position 13708 and the Cytb gene at position 15257. Thes e DNA variants have been described in a number of neurologic disorders , but their pathogenetic potential is unclear. Patient 2 showed the sa me DNA alterations and an additional mtDNA variant at position 15812 i n the Cytb gene. The principal neurohistologic features of the 2 atrop hic brains presented here include: subtotal selective neuronal cell lo ss in the cortex and, to a lesser degree, in the basal ganglia (claust rum, putamen, globus pallidus), sparing palaeocortex and periarchaeoco rtex, and a very characteristic and diagnostic feature was detachment of astrocytic processes from capillary walls resulting in pericapillar y space formation. These pericapillary spaces were partially filled wi th macrophages. The spaces were not associated with total breakdown of the blood vessel walls as demonstrated by the absence of erythrocytes , lymphocytes, or polymorphonuclear leukocytes outside the vascular be d of the brain; progressive subcortical encephalopathy, as it is seen in subcortical dementia (Biswanger), but lacking arterial lipohyalinos is. The cerebral grey and white matter revealed cuffing of arteries an d arterioles by adventitial macrophages. The neocortical and subcortic al changes were accompanied by myriads of activated macrophages filled with lipids. The pathology of our 2 cases differs from that of other neurodegenerative disorders and we suggest the term of ''disseminated neocortical and subcortical encephalopathy (DNSE) with widespread acti vation of brain macrophages''.