Aetiology
Despite improvements in diagnostic technologies, the aetiology of focal seizures is identified in only about one third of cases.
Any insult to the brain may result in the development of focal epilepsy. Examples include:
Traumatic brain injury.[7] Penetrating head injuries have the highest risk for the development of epilepsy.[8] Closed head injury (skull fracture or >30 minutes of unconsciousness or amnesia) leads to a significantly increased risk for the development of seizures.[9] Risk may be slightly elevated even if amnesia lasts less than 30 minutes.[10]
Central nervous system (CNS) infection.[11] The presumed mechanism is an inflammatory process involving the CNS. The more severe the CNS infection, the more likely it is to contribute to seizure development.
Brain tumours. Epilepsy is common in patients with glioneuronal tumours and glioma, and is also associated with meningioma and brain metastases.[12] Low-grade tumours seem more epileptogenic than high-grade tumours.[12][13] One case series suggested that 28% of patients undergoing surgery for brain tumours experience seizures.[14]
Malformations of cortical development (MCDs). These are characterised by abnormal cortical structures or heterotopic grey matter resulting from disrupted cerebral cortex formation. The cause is mostly genetic, but infectious, vascular, and metabolic aetiologies have also been reported. It is estimated that 25% to 40% of treatment-resistant childhood epilepsy is attributable to MCDs, and that at least 75% of patients with MCDs have epilepsy.[15][16]
Intracranial vascular malformations. Seizures are a common presentation in patients with intracranial vascular malformations such as arteriovenous malformations and cavernous angiomas. Seizures may occur de novo or be secondary to intracerebral haemorrhage.[17]
Stroke. Risk of seizure activity is at least 3 times higher after a stroke, but prophylactic anticonvulsant drug therapy is typically not recommended.[18][19]
Alzheimer's disease and non-Alzheimer's dementia. Both have been associated with seizure development.[20]
Perinatal injury. This seems to be particularly the case when there is coexistent neurological handicap with concomitant intellectual disabilities (e.g., cerebral palsy).[21]
Family history. Related to the development of focal epilepsy, although this is not a simple relationship. Some syndromes are thought to be due to inheritance of a single gene (familial temporal lobe epilepsy), while others have a complex inheritance (idiopathic focal epilepsies and cryptogenic/symptomatic focal epilepsies).[22][23]
Benign focal epilepsies of childhood are a group of idiopathic syndromes known to cause focal seizures in developmentally and neurologically normal children. They include benign childhood epilepsy with centrotemporal spikes and childhood epilepsy with occipital paroxysms.[24] These syndromes follow a benign course and usually remit prior to adulthood.
Neurocutaneous syndromes such as neurofibromatosis, Sturge-Weber syndrome, and tuberous sclerosis may result in focal or generalised seizures.
Pathophysiology
The pathophysiology of human epilepsy is complex and not completely understood. Experimental studies in animal models of epilepsy have elucidated potential pathophysiological mechanisms; e.g., kindling, a process by which repeated subthreshold electrical stimulation of specific neuroanatomical structures (e.g., amygdala, hippocampus) leads to the development of electrographical and then focal clinical seizures, which worsen in severity over time. The kindling model has been used to study the process of epileptogenesis related to certain types of focal epilepsy.[25]
After a causative event (e.g., significant head trauma) there may be a latent period (and sometimes a second 'hit') before clinical development of seizures.
Neurochemical and neurophysiological features thought to be relevant to the development of focal seizures include:
Neurotransmitter disturbances (e.g., an imbalance between inhibitory gamma-aminobutyric acid [GABA]-ergic and excitatory glutaminergic neurotransmitters)
Alterations in neuronal and glial cell structures, such as voltage-gated sodium channels, voltage-gated calcium channels, gap junctions (connexins), SV2A synaptic protein vesicles, G-protein-coupled receptors, A or M voltage-gated potassium channels, and ionotropic glutamate receptors.[26][27][28]
Several anticonvulsant medications target these mechanisms. Identifying other targets presents an opportunity for new drug development.
Classification
International League Against Epilepsy (ILAE) report of the Commission on Classification and Terminology, 2017[1][3]
Focal-onset seizures
Aware/impaired awareness (optional)
Motor-onset
Automatisms
Atonic
Clonic
Epileptic spasms
Hyperkinetic
Myoclonic
Tonic
Non-motor onset
Autonomic
Behaviour arrest
Cognitive
Emotional
Sensory
Focal to bilateral tonic-clonic
Generalised-onset seizures
Unknown-onset seizures.
In 2017, ILAE guidelines for seizure classification were revised to include the following:
'Partial' becomes 'focal'
Awareness is used as a classifier of focal seizures
The terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalised are eliminated
New focal seizure types include automatisms, behaviour arrest, hyperkinetic, autonomic, cognitive, and emotional
Atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalised onset
Focal to bilateral tonic-clonic seizure replaces secondarily generalised seizure
New generalised seizure types are: absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic
Seizures of unknown onset may have features that can still be classified.
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