The Causes of Epilepsy
Epilepsy or seizure disorder  is a physical condition that occurs when there is a sudden, brief change in how the brain works. When
brain cells are not working properly, a person's consciousness, movement, or actions may be altered for a short time - epileptic
seizures.
Anneger JF and Co-workers at The University of Texas Health Science Center at
Houston suggested various possible causes for epilepsy such as traumatic brain
injuries, central nervous system infections, cerebrovascular disease, brain tumors,
neurodegenerative diseases, developmental disabilities, perinatal insults, and
familial factors in their review article. [6]

Genetic Disorders

Sánchez-Carpintero Abad R (rsanchezc@unav.es) from Clinica Universitaria de
Navarra, pointed out that genetic factors contribute to the origin of different
epilepsies and most are idiopathic epilepsy. However, the most common forms of
epilepsy are not caused by single mutations but by a combination of polymorphisms,
the changes generate an alteration in neuronal excitability. In some syndromes,
genetic alterations and their consequences lead to the therapeutic response to
different drugs. [1]

Jaeken J. (jaak.jaeken@uz.kuleuven.ac.be) from University Hospital Gasthuisberg,
Belgium, stated that genetic disorders of gamma-aminobutyric acid (GABA),
glycine, and serine metabolism and of the GABA and glycine receptors can be
causes of epilepsy. For example, pyridoxine-dependent convulsions and the
GABA(A) receptor defects are pure epileptic disorders and they both respond well
to treatment. The convulsions associated with 3-phosphoglycerate dehydrogenase
deficiency can be completely treated with amino acid therapy. [2]

Disorders

Sisodiya SM (sisodiya@ion.ucl.ac.uk) at The University College London wrote that
malformations of of cortical development (MCD) are important causes of chronic
epilepsy in her review article. [3] Focal cortical dysplasia, periventricular heterotopia,
polymicrogyria, band heterotopia and lissencephaly, dysembryoplastic
neuroepithelial tumours, and microdysgenesis enlighten the malformations of of
cortical development. [3]

Masukawa LM and co-workers at the University of Pennsylvania School of Medicine
believed paroxysmal discharges are critical for the development of epilepsy. The
presence of paroxysmal discharges in the epileptic human dentate gyrus provides a
physiologic basis for hyperexcitability that may initiate seizure discharges during the
development of epilepsy. [4] Paroxysmal discharges are a more common feature of
tissue from temporal lobe epileptic patients than has been reported previously. Hilar
cell loss and weakened synaptic inhibition could provide conditions favorable for the
activation of N-methyl-D-aspartate acid (NMDA) receptors that would allow
triggering of paroxysmal discharges that normally never are evoked in dentate
granule cells in nonepileptic humans. [4]

As the dentate gyrus in normal animal tissue is not susceptible to intrinsic bursting
behavior and is characterized by a relatively short duration excitatory postsynaptic
potential even under pharmacologic disinhibition, paroxysmal discharges in the
epileptic human dentate gyrus become an important clue to understanding the
prerequisite conditions for seizure discharge. [4]

Age

Seizures and epilepsy are common problems in older adults. Although, the highest
incidence of seizures and epilepsy occurs in individuals more than 65 years of age.
[5]

Injury

Temkin NR at the University of Washington, Seattle noticed that post-traumatic
seizures often occur after severe head injury. Acutely, these seizures complicate
management of the head-injured patient by increasing intracranial pressure and
causing postictal decreases in level of consciousness. In the long term, epilepsy can
have a negative effect on the patient's functioning and integration into society. The
more severe the head injury, the more likely that post-traumatic seizures will occur.
The risk of late seizures exceeds 30% for patients with penetrating head injury,
intracerebral hematoma, subdural hematoma, depressed skull fracture, or seizure
within the first week after injury. Late post-traumatic seizures are treated the same
as any epileptic seizures of the same type. Phenytoin and carbamazepine are
effective in preventing seizures in the first week after head injury, but are not effective
in preventing late seizures. Temkin NR further suggested that both additional
antiepileptic drugs and neuroprotective agents that may lessen the damage that
leads to seizures are being investigated to determine if they are effective in
preventing the occurrence of post-traumatic epilepsy. [6]

Diseases

Ettinger AB at State University of New York at Stony Brook wrote that stroke is the
most common cause of seizures in adults, especially in the elderly, while tumor is
another major cause for people aged from 25 to 64. Cysts and vascular
malformations are becoming common causes for epilepsy.  [7]

Cancer Drugs

Singh G from Dayanand Medical College, India, suggested that intracranial
metastasis, cancer drugs and metabolic disturbances are the most common
causes. Several drugs used in the treatment of cancer, or complications arising from
their use, can trigger seizures through varied mechanisms. [8]

Reference
[1] Sánchez-Carpintero Abad R, et al, Genetic causes of epilepsy. Neurologist. 2007 Nov;13(6 Suppl
1):S47-51. [2] Jaeken J. Genetic disorders of gamma-aminobutyric acid, glycine, and serine as causes of
epilepsy. J Child Neurol. 2002 Dec;17 Suppl 3:3S84-7; discussion 3S88. [3] Sisodiya SM. Malformations of
cortical development: burdens and insights from important causes of human epilepsy. Lancet Neurol.
2004 Jan;3(1):29-38. [4] Masukawa LM, et al, Physiological and anatomical correlates of the human
dentate gyrus: consequences or causes of epilepsy. Adv Neurol. 1999;79:781-94. [5] Sirven JI. Epilepsy in
older adults: causes, consequences and treatment. J Am Geriatr Soc. 1998 Oct;46(10):1291-301. [6]
Annegers JF, Rocca WA, Hauser WA. Causes of epilepsy: contributions of the Rochester epidemiology
project. Mayo Clin Proc. 1996 Jun;71(6):570-5. [6] Temkin NR, Haglund MM, Winn HR. Causes, prevention,
and treatment of post-traumatic epilepsy. New Horiz. 1995 Aug;3(3):518-22. [7] Ettinger AB. Structural
causes of epilepsy. Tumors, cysts, stroke, and vascular malformations. Neurol Clin. 1994
Feb;12(1):41-56. [8] Singh G, et al, Seizures and epilepsy in oncological practice: causes, course,
mechanisms and treatment. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):342-9.

The treatments for Epilepsy (General)
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