1st Year MBBS, Islamabad Medical and Dental College
Epilepsy is an electrophysiological disorder of the brain, characterized by recurrent seizures. Epilepsy directly affects 50 million people worldwide, approximately 0.6–1.5% of the world’s population. Infection in brain, high fever, tumor and stroke can cause epilepsy in addition to genetic factors. Epilepsy imposes a great economic burden on the health care systems of countries also there is stigma and discrimination against the patient and their family in the community, workplace, school and home. Severe emotional distress, extreme social isolation and behavioral disorders affect many patients with epilepsy. Electroencephalogram (EEG) is a test that records the abnormalities in the brain waves and measures electrical activity of the brain, and is mostly used in the diagnosis and analysis of epileptic seizures. 1
Causes of Epilepsy
The causes of epilepsy are unknown. The word epilepsy (Greek word epilambanein that means to be seized) does not specify anything about the cause’s epilepsy or about the severity of seizures, sometimes epilepsy is caused due genetic factors, but epilepsy can also outcome from brain injuries caused by hard blows to the head, stoke, tumors, high fever or infections.2 In young children genetics plays an important role in causing epilepsy, but it can be a factor for people of any age.3 The genetic causes of neonatal epilepsy can be grouped into the following categories:
Deformities of cortical development
Abnormal formation of the cortical plate caused by abnormalities in the cerebral cortex can cause epilepsy.4
Epilepsy genes: genes that cause epilepsies or syndromes with epilepsy (OMIM, HGMD, and Epilepsy Gene) 5
Cellular alterations that can cause epilepsy include neurodegeneration, dendritic remodeling, gliosis, neurogenesis, incursion of inflammatory cells, axonal injury, angiogenesis axonal sprouting, changes in extracellular medium, and abnormally developed channelopathies.6
An increased risk of epilepsy development due to metabolic abnormality in affected individuals. Metabolic epilepsy cannot be treated by commonly used antiepileptic drugs as they do not address its root cause.7
Epilepsy is related to not only to neuronal cells but also to other brain cells, such as glial cells and vascular cells. Both glial cells and endothelial cells express VEGF receptors thus, these cells are likely affected by increases in VEGF during seizures, which in turn causes vascular abnormalities. 8
During the development of epilepsy, the presence of paroxysmal discharges in the epileptic human dentate gyrus provides a physiologic basis for hyperexcitability which may initiate seizures. 9 Seizures may be caused by abnormality of potassium conductance, deficiency in the membrane ATPases related to ion transport may cause neuronal membrane to become unbalanced or a defect in the voltage activated ion channels.10 Causes of Idiopathic epilepsies are mutations in genes that encode for ligand gated ion channels, which are mainly involved in synaptic transmission or ion channels or voltage-gated ion channels, which are important for action potential generation and accessory subunits. 11 Acquired epilepsy is caused by Traumatic brain injury (TBI), and it can intensify the seizure severity in individuals with pre-existing epilepsy. TBI is an example of the process of epileptogenesis in neurology. 12
Generalized epilepsy Seizures arise suddenly in a generalized fashion all over the brain.13 Focal epilepsy Localized epileptic discharge in a small group of neurons. Temporal lobe epilepsy most common type of focal epilepsy.14
Types of Seizers
- Simple Focal Seizures
- Simple focal seizures occur for a short amount of time lasting less than one minute.
- Complex Focal Seizure
- Patients may stare blankly into space, or experience automatisms.
Absence seizure cause blank outs for a few seconds. These are also known as petit mal seizures. Most commonly occur in children but don't have any long-term effects. Period of hyperventilation set of these seizures.8
Sudden loss of muscle strength is characteristic of atonic seizures.
A seizure involving both tonic (stiffening) and clonic (twitching or jerking) segments of muscle activity.
A brief seizure with shock-like jerks of a muscle or a group of muscles.9
Effects on performance of daily life tasks and mental health
For thousands of years people living with epilepsy suffer from stigma that is based on misunderstandings, misinterpretations and myths. Loneliness and social avoidance are negative attitudes that prevail in adolescents and adults in both school and workplace. Having unstable mental health, antisocial issues and being potentially violent toward others are common views on people with epilepsy. 25 percent of adults having epilepsy describe social stigma as a result of their epilepsy. Fear of rejection and shame or loneliness are common emotions that come with epilepsy diagnosis. It has significant psychosocial and social impact. 15
Increased risk of mortality is associated with epilepsy; however, it is rarely due to the epilepsy itself.
Suicide is the principal cause of death among persons with epilepsy. From 30 studies comprising of 51,216 persons showed, 188 people committed suicide and died. 3
International classification of epileptic seizures8
In low-income countries or third world countries the burden of epilepsy is more than twice that in highincome countries, due to higher incidence of risk factors. Most deaths in low-income countries are related to untreated epilepsy. 15 Substantial stigma is associated with epilepsy in low-income countries, acts as a barrier for accessing biomedical treatment and becoming integrated within society. Inexpensive antiepileptic drugs can be used to control seizures to a great degree, but in underprivileged areas the supply and quality of these drugs can be inconsistent and unreliable. Medications and therapies use to treat Epilepsy 20-30% of epileptic patients whose seizures are not fully controlled with available antiepileptic drugs (drug resistant epilepsy), have an increased risk of death. Adverse effects from antiepileptic drugs include psychiatric and somatic comorbidities. Newer drugs are more effective have brought more treatment options. Drugs such as levetiracetam cause fewer drug interactions and less hypersensitivity than older ones. Though, the risk of drug resistance epilepsy is not averted. Development of epilepsy in patients at high risk, such as those with a traumatic brain injury is also not averted. 16 Approximately 25% of patients with generalized epilepsy and 30% of patients with focal epilepsy have epilepsy that is not controlled by medications. These patients are given multiple AEDs, which have adverse effects including disabling seizures and side effects. Second-generation AEDs are much safer and better tolerated by epileptic patients than the older AEDs. For those patients whose seizures are not controlled by AEDs surgery and Vagus nerve stimulator can be important therapeutic options. 17
The terms antiepileptic and anticonvulsant are used inter changeably. An agent that blocks experimentally produced seizures in laboratory animals is called anticonvulsant and a drug used medically to control epilepsies is an antiepileptic drug.
- Any causative factors of epilepsy must be treated first, e.g., cerebral neoplasm.
- The patient should be educated about the disease, the duration of treatment and need for compliance.
- Triggering factors must be avoided, e.g., sleep deprivation, emotional stress and alcohol.
- Natural variation should be anticipated, e.g., seizures may occur particularly or exclusively around periods in women.
- Antiepileptic drug should be given only if required (seizure type and frequency), i.e., more than one fit every 6-12 months. 18
- Acharya UR, Sree SV, Swapna G, Martis RJ, Suri JS. Automated EEG analysis of epilepsy: a review. Knowledge-Based Systems. 2013 Jun 1;45:147-65.
- Bandstra NF, Camfield CS, Camfield PR. Stigma of epilepsy. Canadian Journal of Neurological Sciences. 2008 Sep;35(4):436-40.
- Pompili M, Girardi P, Tatarelli R. Death from suicide versus mortality from epilepsy in the epilepsies: a meta-analysis. Epilepsy & Behavior. 2006 Dec 1;9(4):641-8
- Whelan CD, Altmann A, Botía JA, Jahanshad N, Hibar DP, Absil J, Alhusaini S, Alvim MK, Auvinen P, Bartolini E, Bergo FP. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain. 2018 Feb 1;141(2):391-408.
- Newton CR, Garcia HH. Epilepsy in poor regions of the world. The Lancet. 2012 Sep 29;380(9848):1193-201
- Gloor P, Fariello RG. Generalized epilepsy: some of its cellular mechanisms differ from those of focal epilepsy. Trends in neurosciences. 1988 Jan 1;11(2):63-8.
- Panayiotopoulos CP. Typical absence seizures and their treatment. Archives of disease in childhood. 1999 Oct 1;81(4):351-5.
- Kandar HK, Das SK, Ghosh L, Gupta BK. Epilepsy and its management: A review. Journal of PharmaSciTech. 2012;1(2):20-6.
- Axeen EJ, Olson HE. Neonatal epilepsy genetics. InSeminars in Fetal and Neonatal Medicine 2018 Jun 1 (Vol. 23, No. 3, pp. 197-203). WB Saunders.
- Masukawa LM, Burdette LJ, McGonigle P, Wang H, O'Connor W, Sperling MR, O'Connor MJ, Uruno K. Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy. Advances in neurology. 1999 Jan 1;79:781-94.
- Schmidt D, Schachter SC. Drug treatment of epilepsy in adults. Bmj. 2014 Feb 28;348. Nadkarni S, LaJoie J, Devinsky O. Current treatments of epilepsy. Neurology. 2005 Jun 28;64(12 suppl 3):S2-11. Jensen FE. Introduction Posttraumatic epilepsy: treatable epileptogenesis. Epilepsia. 2009 Feb;50(Suppl 2):1.
- Liu W, An D, Xiao J, Li J, Hao N, Zhou D. Malformations of cortical development and epilepsy: A cohort of 150 patients in western China. Seizure. 2015 Nov 1;32:92-9. Wang J, Lin ZJ, Liu L, Xu HQ, Shi YW, Yi YH, He N, Liao WP. Epilepsy-associated genes. Seizure. 2017 Jan 1;44:11-20. Pitkänen A, Lukasiuk K. Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy & behavior. 2009 Jan 1;14(1):16-25. Steinlein OK. Genetic mechanisms that underlie epilepsy. Nature Reviews Neuroscience. 2004 May;5(5):400-8. Ogaki A, Ikegaya Y, Koyama R. Vascular abnormalities and the role of vascular endothelial growth factor in the epileptic brain. Frontiers in pharmacology. 2020:20.
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