1. Neuropathology of epilepsy: epilepsy-related deaths and SUDEP
Maria Thom 
Diagnostic Histopathology 
Volume 25, Issue 1, Pages (January 2019)
DOI: /j.mpdhp
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2. Figure 1
Block sampling strategy in suspected SUDEP or other epilepsy related deaths post mortem. Lines indicate approximate coronal levels for block sampling, following hindbrain removal, as shown in the slices. Sample should be taken of any macroscopic abnormality. The samples 1–6 are shown only on one hemisphere to illustrate the anatomy, but paired blocks are recommended as good practice. The numbered blocks correspond to: 1. Vascular watershed region/Frontal watershed regions (F1/2) for assessment of any acute hypoxic/ischaemic damage, meningitis, encephalitis, chronic neuronal loss (from previous seizures or episodes of status epilepticus e.g. laminar atrophy). 2. Insular cortex/basal ganglia to assess acute neuronal injury, hypoxic/ischaemic damage, meningitis, encephalitis. 3. Amygdala to evaluate any chronic neuronal loss or acute neuronal injury, hypoxic/ischaemic damage, limbic encephalitis, chronic astrocytosis. 4. Hippocampus to evaluate any acute neuronal injury (CA1), hypoxic changes, limbic encephalitis, hippocampal gliosis or sclerosis, malformation or neurodegenerative disease. 5. Thalamus to evaluate any chronic or acute neuronal injury and any chronic regional gliosis. 6. Temporal cortex (T1/2) to assess for meningeal inflammation, encephalitis, gliosis, global hypoxic changes, chronic atrophy, traumatic brain injury and any neurodegenerative pathology. 7. Cerebellar cortex to assess for acute or chronic atrophy (Purkinje cell loss and gliosis), and any inflammation. 8. Medulla to assess for any inflammatory disease or acute neuronal injuries. The standard stains that may be useful in analysis in assessment of any identified epilepsy-related pathologies is included in Table 3. This sampling strategy corresponds to the Royal College of Pathologists guide for epilepsy deaths.
Diagnostic Histopathology  , 23-33DOI: ( /j.mpdhp )
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3. Figure 2
Macroscopic brain appearances in epilepsy-related deaths and sudden deaths. (a). Fixed brain in patient with SUDEP showing mild brain swelling and effacement or fullness of the gyri over the hemisphere. (b). Another SUDEP case in a child which has been sliced in sagittal plane, one hemisphere was frozen and one fixed for histology (shown here) with evidence of effacement of the gyri but not subfalcine herniation. (c). A further SUDEP case with mild brain swelling and uncal grooving (arrowed) but without tissue necrosis. (d). A sudden death due to a traumatic subarachnoid haemorrhage following seizure. (e). Sudden death in a patient with epilepsy with an oligodendroglioma (arrowed) showing microcystic changes and mild expansion of the grey matter. (f). Sudden death in patient with recent onset poorly controlled epilepsy where the fresh brain showed collapse and haemorrhage in CA1 sector of the hippocampus (arrows) and histology confirmed a limbic (autoimmune) encephalitis. (g). Coronal slices through a fixed brain showing a large old temporal lobe contusion (arrowed) following assault; this patient had a sudden death but no history of seizures. (h). SUDEP in a patient with epilepsy and history of RTA with a small region of brain injury compatible with an old contusion (arrows). (i). SUDEP case in patient with early onset of epilepsy and cortical malformation with a microgyric pattern involving both occipital lobes. On histology this correlated with focal cortical dysplasia (type IIId). (j). Witnessed SUDEP following two seizures in a patient with refractory epilepsy due to a known arteriovenous malformation showing numerous, tortuous ectatic changes on the meningeal surface and in (k) abnormal extension of vessels into the underlying parenchyma with cavitation. (l). A SUDEP case on which the brain appeared macroscopically normal but histology confirmed evidence of a cortical dysplasia.
Diagnostic Histopathology  , 23-33DOI: ( /j.mpdhp )
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4. Figure 3
Comparison of the relative incidence of common epilepsy neuropathologies in surgical series (blue) compared to reports in SUDEP (red) and non-SUDEP post mortem series (green). Each point for each pathology represents a different series. Adapted from reference 12.
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5. Figure 4
Histopathological findings in hippocampal sclerosis in epilepsy. A surgical case of type 1 hippocampal sclerosis is shown with neuronal loss in CA1 and CA4 more clearly confirmed with MAP2 neuronal marker and gliosis with GFAP in the same regions. The zinc transporter 3 protein (ZnT3) highlights aberrant sprouting of axons in the dentate gyrus (arrowed).
Diagnostic Histopathology  , 23-33DOI: ( /j.mpdhp )
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6. Figure 5
Diagram of possible pathways and risk factors that could lead to SUDEP.
Diagnostic Histopathology  , 23-33DOI: ( /j.mpdhp )
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