Epilepsy

Epilepsy is a common neurological disorder that is characterized by a predisposition to having epileptic seizures and can take many clinical forms and have many potential etiologies.

Epilepsy is defined by the International League Against Epilepsy (ILAE) as ¹:

• at least two or more unprovoked (or reflex) seizures occurring more than 24 hours apart; or

• one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures, occurring over the next 10 years; or

• diagnosis of an epilepsy syndrome

Drug resistant epilepsy is defined by the International League Against Epilepsy (ILAE) as epilepsy in which sustained seizure freedom (of at least 12 months) has not been achieved despite adequate trials of two tolerated, appropriately chosen and used antiseizure medications, whether as monotherapies or in combination ¹⁶.

Epidemiology

Epilepsy is very common, with approximately 3% of the population affected at some point in their life ².

Clinical presentation

The hallmark clinical feature of epilepsy is that of epileptic seizures, which may have a variety of semiologies depending on the type of seizure and epilepsy. However, there are other important clinical features that may accompany epileptic seizures in epilepsy ³:

• psychiatric co-morbidity, e.g. anxiety, depression, functional seizures (psychogenic non-epileptic seizures)

• physical effects/complications of epileptic seizures, e.g. injury, death (including sudden unexpected death in epilepsy (SUDEP)), neurocognitive deterioration

• social effects/complications: e.g. lower education levels, lower employment rates with fewer options, limitations on recreational activities, stigmatisation

• antiseizure medication side-effects, e.g. neurocognitive deterioration, weight gain, rash, osteoporosis, hair loss

Pathology

Epilepsy is classified by the International League Against Epilepsy (ILAE) according to a three-level framework ⁴:

• seizure type ⁵

  • focal (preferred term to 'partial') onset

    • may have awareness (preferred term to 'simple partial') or impaired awareness (preferred term to 'complex partial' or 'dyscognitive')

    • may be motor onset or non-motor onset (e.g. sensory, autonomic)

    • may progress from focal to bilateral tonic-clonic seizures

  • generalized

    • may be motor seizures, e.g. tonic-clonic (preferred term to 'grand mal') seizure, clonic seizure, tonic seizure, myoclonic-tonic-clonic seizure, myoclonic-atonic seizure, atonic seizure

    • may be non-motor or absence (preferred term to 'petit mal') seizure

  • unknown

• epilepsy type

  • focal

  • generalized

  • combined generalized and focal

  • unknown

• epilepsy syndrome

  • e.g. Dravet syndrome, Lennox-Gastaut syndrome, idiopathic (genetic) generalized epilepsy

Etiology

There are a myriad of etiologies, however, in adults with new onset of seizures ~50% will not have a determinable cause ². The International League Against Epilepsy (ILAE) have proposed the following etiological classification ⁴:

• structural etiology

  • acquired, e.g. stroke, cerebral palsy, post-meningitis, traumatic brain injury, vascular malformations, mesial temporal sclerosis, meningoencephaloceles, tumors (e.g. long-term epilepsy-associated tumors, low-grade gliomas, etc.), porencephalic cysts

  • genetic, e.g. focal cortical dysplasia, grey matter heterotopia

• genetic etiology

  • e.g. channelopathies (e.g. Dravet syndrome, fragile X syndrome), neurocutaneous syndromes (e.g. tuberous sclerosis), chromosomal abnormalities (e.g. Down syndrome, Klinefelter syndrome, ring chromosome 20 syndrome)

  • note that some genetic etiologies may also be structural etiologies in this classification

• infectious etiology

  • e.g. neurocysticercosis, tuberculosis, toxoplasmosis, cerebral malaria, subacute sclerosing panencephalitis, congenital CMV

  • note that this is not referring to seizures occurring in the setting of an acute CNS infection

• metabolic etiology

  • e.g. porphyria, GLUT1 deficiency syndrome, cerebral folate deficiency, mitochondrial disorders

• immune etiology

  • e.g. autoimmune encephalitis, CEC syndrome, steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)

• unknown etiology

​Radiographic features

MRI

MRI brain is the radiographic modality of choice ². Please see articles on specific conditions listed above for imaging features. There are a number of MRI protocols that can be used to investigate patients with seizures.

Nuclear medicine

SPECT

If perfusion neuroimaging is performed during a seizure (i.e. ictal SPECT), it can be useful for localizing the epileptogenic zone ^6,7. Postictal SPECT and interictal SPECT are less sensitive than ictal SPECT ¹², however, ictal-interictal SPECT subtraction, particularly with MRI co-registration (i.e. subtraction ictal SPECT co-registered to MRI (SISCOM)), can be highly sensitive ^13,14.

Commonly used radiopharmaceuticals for SPECT epilepsy imaging include technetium 99m (^99mTc) ethyl cysteinate dimer (ECD) and ^99mTc–hexamethyl propylene amine oxime (HMPAO), which allow imaging of regional cerebral blood flow (rCBF) ¹⁸.

FDG-PET

May show an area of hypometabolism corresponding to an epileptogenic zone. FDG-PET has been largely replaced by MRI but can be used in conjunction for localization of an epileptogenic zone ⁸.

PET-TSPO

Translocator protein (TSPO) is a molecular marker for glial activation and neuroinflammation. Quantification of TSPO using PET has been used to study epileptogenic zone. For example, increased TSPO levels can be seen in the epileptogenic zone within temporal lobes in patients with temporal lobe epilepsy ^9,10.

Treatment and prognosis

Management of epilepsy is potentially complex, and may involve ^2,3,15,17:

• lifestyle restrictions, e.g. driving restrictions, restrictions on employment, limiting exposure to drugs and alcohol

• antiseizure medications, either as monotherapy or in combination, and ketogenic diet

  • describing these medications as 'antiseizure' is the International League Against Epilepsy (ILAE) preferred terminology to 'antiepileptic' or 'anticonvulsive' ¹¹

• non-invasive neuromodulation therapies, e.g. repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS)

• epilepsy surgery, e.g. stereoelectroencephalography (sEEG) with thermocoagulation, laser interstitial thermal therapy (LITT), invasive neuromodulation therapies (e.g. vagal nerve stimulation, deep brain stimulation), surgical resection

• specific management of psychosocial effects and iatrogenic complications

See also

• epilepsy protocol (MRI)

• status epilepticus