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immunolabelling for stem cell marker CD34. The identification of peri-lesional cortical
abnormalities in the vicinity of glioneuronal tumours raises the question not only of common
biological origins but, importantly, where the intrinsic epileptogenicity arises.

Vascular malformations in epilepsy surgery
Vascular malformations form up to 10% of lesions encountered in epilepsy surgical series and
the main types are arteriovenous malformations (AVM) and cavernomas, with telangiectatic or
angiodysgenetic lesions more rarely encountered. Although regarded as congenital, these lesions
are dynamic and may even rarely arise de novo. Epilepsy is a common presenting clinical feature
in 17% of AVM and is the most common presenting symptom in cavernomas (79%). Seizures
may be generalised or partial115. Common features to both AVM and cavernomas include
extensive peri-lesional gliosis and tissue microhaemorrhages indicative of sub-clinical bleeds.
The possible mechanisms inducing epilepsy include local ischaemia as result of arterio-venous
shunting, the marked associated peripheral gliosis, haemosiderin deposition or secondary
epileptogenesis occurring in the temporal lobe.

Hamartomas in epilepsy surgery
Hamartomas in epilepsy are a poorly defined pathological group forming a small number of cases
in different epilepsy surgical series. Glio-neuronal hamartomas have been described in various
cortical locations, particularly temporal and frontal lobes, composed of circumscribed masses of
mature but haphazardly arranged cell types, sometimes reported in association with adjacent
cortical dysplasia116. The imaging characteristics of glio-neuronal hamartomas are variable117,118;
their lack of growth and mitotic activity help to distinguish these lesions from low-grade tumours
and they tend not to recur116. The hypothalamic hamartoma has a strong association with
intrinsic subcortical epileptogenesis and gelastic seizures, and may be associated with the
development of secondary cortical epileptogenesis119. Unlike the tuberous sclerosis complex,
hamartomas or malformative cortical lesions are relatively rarely reported in neurofibromatosis
type 1 (NF1)120, a syndrome in which epilepsy occurs in up to 6% of patients121. NF2 can be
associated with multiple cortical glial-microhamartomas that are often incidental findings at post
mortem. Interestingly, the presumed hamartomatous cell proliferation of meningioangiomatosis
(MA), when associated with the NF2 complex, does not clinically manifest with seizures whereas
in sporadic MA over 80% of patients present with epilepsy122. The more common sporadic form
of MA is typically solitary and EEG suggests the epileptogenicity is confined to the adjacent
cortex; seizures may persist in over half of patients following surgical treatment123.

Autoimmune encephalitis
Patients with antibodies to intracellular or surface antigens can present with acute onset of
epilepsy, psychiatric illness, cognitive decline and underlying limbic encephalitis (e.g. GAD,
LGI1)124. Rasmussen’s encephalitis (RE) is a rare sporadic syndrome of presumed autoimmune
aetiology typically presenting in childhood with intractable seizures and associated with
progressive unilateral hemispheric atrophy and neurological deficit. The severity of the
inflammatory process and the extent of the cortical scarring vary with the duration of the disease
process and traditionally has been divided into four stages. The early stages (1 and 2) are
characterised by more active chronic inflammation and later stages (3 and 4) with less active
inflammation and more extensive scarring125. Inflammatory infiltrates in the cortex consist
mainly of T lymphocytes (CD8>CD4+) with perivascular and perineuronal clusters126. B
lymphocytes are less frequently present in the perivascular cuffs and plasma cells are rare.
Widespread activation of microglia may be seen as well as microglial clusters and nodules (see
Figure), but macrophage infiltrates are less common. Patchy neuronal degeneration,
neuronophagia and neuronal dropout are present in the early stages.