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Cerebrovascular epilepsy
Cerebrovascular disease is an important contributor to new cases of epilepsy developing over
the age of 60 and is largely responsible for the increased age-related incidence at this time of
life. A number of studies would suggest that between 5 and 10% of patients with a clinical
history of stroke due to occlusive vascular disease will develop epilepsy. However, covert
cerebrovascular disease may be much more common on the CT scans of patients with late-
onset epilepsy when compared with age-matched controls5. The Oxford Community Stroke
Study found that 2.8% of patients had a seizure before their first stroke. A total of 2.1% had
a seizure within 24 hours of the stroke and 7.1% had seizures subsequently. Actuarial analysis
estimated that the one-year cumulative risk of a post-stroke seizure was 4.1% after cerebral
infarction, 18.2% after primary intracerebral haemorrhage and 27.8% after subarachnoid
haemorrhage.

Epilepsy also complicates cerebral aneurysms whether or not they have bled or been operated
upon (see above). AVMs are also a cause of epilepsy in earlier life. Epilepsy is present in
approximately 2025% of patients presenting with AVMs and the risk of developing de novo
epilepsy in AVM is approximately 1% per annum. Haemorrhage and surgical treatment
appear to be the major factors that increase this risk.

Autoimmune epilepsy
Seizures are a common presenting symptom in autoimmune neurologic disorders, particularly
in limbic encephalitis or multifocal paraneoplastic disorders6–9. Autoantibodies recognised
with paraneoplastic limbic encephalitis include antineuronal nuclear antibody type 1,
collapsin response-mediator protein 5 (CRMP-5), and Ma2. Voltage-gated potassium channel
(VGKC) complex and glutamic acid de-carboxylase 65 (GAD65) antibodies, often
nonparaneoplastic in aetiology, have been reported in patients with limbic encephalitis and
idiopathic epilepsy with AED-resistant seizures10,11. Newly identified autoantibody
specificities that strongly correlate with clinical seizures include N-methyl-D-aspartate
(NMDA), γ-aminobutyric acid B12,13 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptors14.

It is clear that the clinical spectrum of auto-immune epilepsy is still unknown. In a series of
patients with epilepsy, VGKC complex antibodies were detected in 10%; NMDA receptor
antibodies, in 7% of newly diagnosed patients; and GAD65 antibodies, in 1.6–1.7% 15. It is
conceivable that only patients with the most severe presentations in this heterogeneous group
are being identified.

Accumulating data support an autoimmune basis in patients with AED-resistant seizures,
including those lacking a typical ‘limbic encephalitis’ phenotype. Identification of an
immune basis is important because adjunctive immunotherapy may slow, halt, or even
reverse the epileptogenic process in these patients. In a cohort study, autoimmune antibodies
were detected in 14% of patients with epilepsy16. This study, along with several case reports
and series, suggested a potential benefit of immunotherapy in improving seizure control.

Recurrent seizures are the early and predominant clinical manifestation in patients with an
autoimmune aetiology. An autoimmune cause is identified most readily in patients who
present with the full syndrome of limbic encephalitis, characterised by subacute memory
impairment with mood disturbance and temporal lobe seizures. The diagnosis of autoimmune
limbic encephalitis is aided by detection of neural autoantibodies with radiological or
pathological evidence of mesial temporal lobe inflammation and in some cases a history of
neoplasia in the preceding five years17.