The neuropathology of intimate partner violence

Abstract

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd-8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd-9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Keywords: Cerebrovascular disease; Chronic traumatic encephalopathy; Diffuse axonal injury; Domestic violence; Neurodegeneration; Traumatic brain injury.

Fig. 1

Ex vivo neuroimaging and detection of subtle vascular neuropathology in IPV. Neuroimaging of frontal lobes at level of striatum (NY6), revealing signal abnormalities in the periventricular white matter (a., left per neuroradiologic convention; box outlines left frontal mirror-image areas of histology in b., c.). Neurohistology of boxed area in a., demonstrating ill-defined zone of myelin pallor on Luxol-fast blue/hematoxylin-and-eosin (b., 20x), as well as localized perivascular rarefaction indicating loss of vascular integrity (arrows) (c., 40x). T1 map of different periventricular white matter region, with signal features of perivascular edema (d.), corresponding to perivascular accumulation of proteinaceous fluid in perivascular space (e., 200x); inset, detail of eosinophilic perivascular fluid, indicating vasogenic edema (400x). Immunostain for fibrinogen indicating leakage of plasma protein (brown reaction product, seen in vessel lumen) into perivascular neuropil (f., 200x)

Fig. 2

Histopathologic evidence of recent and old diffuse axonal injury in IPV. APP immunohistochemistry (brown reaction product) showing loose groupings (a., 200x; NY9, corpus callosum), or many clusters (arrows) of beaded axons (b., 100x; NY6, corpus callosum), indicating recent traumatic axonal injury, distinct from sparse staining in normal controls (not shown) or from the “zigzag” staining pattern expected in ischemic damage (not shown). CD68 immunostains highlighting single small (c., 200x; NY12, posterior limb of internal capsule) or larger grouped (d., 200x; NY6, corpus callosum) clusters of microglia and macrophages, considered markers of prior diffuse axonal injury. Microscopic focus of old, organizing diffuse axonal injury as detected by APP-immunopositive linear swollen axons (arrow), amid many unstained macrophages (arrowheads) (e., 200x; NY11, internal capsule). See text for discussion

Fig. 3

Histopathologic evidence of old vascular injury in IPV. Iron stains highlighting deposition of iron (blue granules; arrows) free and in macrophages in neuropil around non-arteriolosclerotic blood vessels in basal ganglia (a., 200x; NY10) and hypothalamus (b., 400x; NY7). Microvessels with arteriolosclerosis denoted by hyaline thickening of walls, and with iron in perivascular neuropil (arrow in c., 200x; NY5, posterior limb of internal capsule), in contrast to an arteriolosclerotic vessel with no iron in perivascular space or parenchyma (d., 400x; NY13). Old microbleeds detected by iron stains in neuropil (arrow) at sites vulnerable to traumatic axonal injury, such as the midbrain (e., around arteriolosclerotic vessel) and pons (f.; both, 400x; NY11). See text for discussion