The Dual Neuropathological Signature of IPV: TBI and Non-Fatal Strangulation

The pathology of brain injury (BI) within the context of Intimate Partner Violence (IPV) is complex and heterogeneous, often involving distinct mechanisms: mechanical traumatic brain injury (TBI) via blunt force head impacts or repetitive head impacts (RHI), and acquired brain injury (ABI) resulting from non-fatal strangulation (NFS) (Dams-O’Connor et al., 2023; Esopenko et al., 2021).

IPV survivors, particularly women, frequently experience both TBI (reported by 57.14% of survivors) and strangulation (reported by 64.28% of survivors in one study) (Daugherty et al., 2020). The resulting neuropathology often reflects a multi-aetiology injury signature (Dams-O’Connor et al., 2023).

I. Pathology Associated with Non-Fatal Strangulation (NFS)

NFS is recognised as a specific form of acquired brain injury (ABI) that can lead to neurological and psychological impairments independent of blunt force trauma (Valera et al., 2009). The primary pathological mechanisms involve vascular and hypoxic injury:

·       Vascular and Hypoxic Damage: Strangulation—whether manual, ligature, hanging, or positional asphyxia—causes restriction of cerebral blood flow and oxygenation, leading to hypoxia and potentially ischaemia (Carlson, 2014).

·       Specific Vascular Lesions: NFS can cause direct damage to critical vascular structures. Approximately 4.0% of strangulation survivors who undergo adequate neuroimaging are diagnosed with carotid artery dissection (Etgen et al., 2023).

·       Physical Signs and Imaging: While immediate visible injuries are often absent, strangulation can cause physical signs like petechiae, dysphagia, and damage to the carotid artery (Carlson, 2014). Advanced postmortem imaging techniques, such as MRI, have confirmed internal soft tissue injuries and haemorrhages, while CT scans can identify fractures related to the neck compression (Deininger-Czermak et al., 2020; Bauer et al., 2024; Bruguier et al., 2019).

·       Psychological Consequences: The event itself, characterised by asphyxia and terror, results in severe psychological consequences such as Post-Traumatic Stress Disorder (PTSD) and anxiety (Carlson, 2014). Furthermore, NFS history is associated with more severe depressive symptoms, even after adjusting for social support (Mittal et al., 2018).

II. Acute and Chronic Pathology of Traumatic Brain Injury (TBI) in IPV

Head impacts, reported by 74% of women experiencing IPV, initiate a cascade of acute cellular damage and long-term neurodegeneration (Adhikari et al., 2023).

A. Acute Cellular Mechanisms

Following a mechanical impact (even mild TBI), the following cellular pathologies occur:

·       Axonal Injury and Cytoskeletal Breakdown: TBI causes diffuse neuronal damage and blood-brain barrier (BBB) leakage (Chen et al., 2022). Diffuse axonal injury (DAI) is a common initial pathology (Johnson et al., 2013). This involves the proteolysis of submembrane cytoskeletal proteins, such as ankyrin-G and $\alpha$II-spectrin, contributing to white matter vulnerability (Reeves et al., 2010).

·       Apoptosis and Oxidative Stress: TBI induces regionally distinct apoptosis in structures such as the injured cortex, white matter, hippocampus, and thalamus (Conti et al., 1998). Oxidative stress is rapidly induced, leading to high levels of markers like F2-isoprostane and reduced total antioxidant reserves in the cerebrospinal fluid (CSF) (Bayir et al., 2002). This oxidative stress and protein modification lead to synaptic dysfunction (Ansari et al., 2008).

·       Neuroinflammation: Inflammation plays a critical role in TBI pathophysiology (Corps et al., 2015; Nizamutdinov et al., 2017). Inflammasome proteins (ASC, caspase-1, NALP-1) are significantly elevated in the CSF of TBI patients and correlate with unfavourable outcomes (Adamczak et al., 2012). Astrogliosis (reactive astrocyte activation) is a major feature of reactive gliosis post-TBI (Becerra-Hernández et al., 2022; Amlerova et al., 2024).

B. Chronic Neurodegenerative Sequelae

For IPV survivors experiencing repetitive head impacts (RHI), the pathology often progresses to chronic neurodegeneration, sometimes resembling Chronic Traumatic Encephalopathy (CTE).

·       Protein Misfolding and Accumulation: Long-term consequences of TBI involve ongoing protein pathology (Dodd et al., 2022). TBI leads to the rapid accumulation of $\beta$-amyloid oligomers/protofibrils and insoluble aggregates (Abu Hamdeh et al., 2017). Widespread tau and amyloid-beta pathology, resembling Alzheimer's disease (AD)-like pathology, has been observed many years after a single TBI (Johnson et al., 2011). Furthermore, TBI induces increased Amyloid Precursor Protein (APP) and phosphorylated tau (p-tau) accumulation, contributing to secondary cell death (Acosta et al., 2016).

·       Chronic Neuroinflammation and Gliosis: Chronic neuroinflammation, involving microglial activation and reactive gliosis, persists for years after a single TBI (Johnson et al., 2013; Shao et al., 2022). This long-term inflammation contributes to neurodegeneration (Chiu et al., 2016). In animal models of repeated mild TBI (r-mTBI), neuroinflammation and white matter pathology progressively worsen over time (Angoa-Pérez et al., 2020).

·       Brain Atrophy and White Matter Loss: TBI is associated with progressive brain volume loss and neurodegeneration (Bigler, 2013). Patients show regional white matter volume loss, decreased fractional anisotropy (FA), and increased mean diffusivity (MD) longitudinally (Bendlin et al., 2006; Farbota et al., 2012). TBI brains may exhibit a significantly "older" predicted brain age compared to chronological age, suggesting accelerated atrophy (Cole et al., 2015).

·       Chronic Traumatic Encephalopathy (CTE) Signature: In the context of RHI, which is common in IPV, the neuropathological signature may include CTE-NC (Dams-O’Connor et al., 2023). Pathognomonic lesions for CTE are defined as p-tau accumulation around small vessels, preferentially located in the cortical sulci (the TBI/CTE group et al., 2015). CTE pathology is characterised by phosphorylated tau accumulation, microgliosis, and astrocytosis (Fesharaki-Zadeh, 2019).

III. Overlap with Neuropsychiatric and Cognitive Impairments

The complex pathology resulting from IPV-related BI (TBI and NFS) contributes directly to chronic neuropsychiatric and cognitive sequelae.

·       Cognitive Impairment: Both single and repetitive mild TBI lead to significant cognitive deficits, including issues with immediate recall, attention, and working memory (de Freitas Cardoso et al., 2019; Dikmen et al., 2017). In the chronic phase, TBI exposure is associated with an earlier onset of cognitive decline and dementia (Iacono et al., 2021; Schaffert et al., 2018).

·       Psychiatric Comorbidity: Post-TBI psychiatric illness is highly prevalent, with depressive episodes (12.8%) and panic disorder (6.7%) reported one year post-injury (Deb et al., 1999). TBI history is also linked to increased rates of apathy, motor disturbances, and earlier anxiety onset during subsequent dementia progression (Bray et al., 2021; Bray et al., 2022). NFS survivors often exhibit symptoms of PTSD, depression, and anxiety (Carlson, 2014).

In summary, brain injury pathology associated with IPV is uniquely characterised by the co-occurrence of mechanical TBI (leading to DAI, chronic neuroinflammation, and potentially CTE-NC) and vascular/hypoxic injury from NFS (leading to potential carotid dissection and hypoxic damage) (Dams-O’Connor et al., 2023). These combined pathological processes result in persistent structural changes, accelerated atrophy, and profound chronic neuropsychiatric deficits (Cole et al., 2015; Fesharaki-Zadeh, 2019).

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