Epilepsy
People who have epilepsy suffer from an abnormality of their brain that causes them to have seizures — generalized convulsions of their body (muscle spasms) or more subtle mental or physical behavioral disturbances lasting from seconds to minutes and typically recurring at varying intervals.[1] Some types of seizures manifest as strange sensations or emotional states, and others, unconsciousness.
In technical terms, the U.S. National Library of Medicine, citing Adams et al.,[2] defines epilepsy as "a disorder characterized by recurrent episodes of paroxysmal [sudden, intense] brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge [discharge of electrical activity by nerve cells]. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology [cause] (e.g., post-traumatic [after an injury]), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal [time related] patterns."[3]
Historical notes relating to epilepsy
The ancient Greeks recognized epilepsy, calling it the Sacred Disease, as they regarded it as inflicted by the gods. But Hippocrates of Cos (460 BCE - ?360 BCE), who recognized that diseases had natural causes, recognized epilepsy as a natural disorder of the brain:[4]
It is thus with regard to the disease called Sacred: it appears to me to be nowise more divine nor more sacred than other diseases, but has a natural cause from the originates like other affections....this disease seems to me to be no more divine than others; but it has its nature such as other diseases have, and a cause whence it originates, and its nature and cause are divine only just as much as all others are, and it is curable no less than the others, unless when, the from [the length] of time, it is confirmed, and has became stronger than the remedies applied....the brain is the cause of this affection, as it is of other very great diseases, and in what manner and from what cause it is formed, I will now plainly declare….
Classification
Benign neonatal epilepsy
Partial epilepsy
Febrile seizures
Generalized epilepsy
Landau-Kleffner syndrome
Myoclonic epilepsy
Post-traumatic epilepsy
Reflex epilepsy
Status epilepticus
Pathophysiology
The overexcitability of the brain in epilepsy predominantly involves the NMDA receptor, a ionic receptor of glutamate. The NMDA receptor uses magnesium to regulate the entry of calcium in neurons and prevent epileptiform activity. Epileptic patients have lower than normal ionic magnesium, although the more common laboratory test, total magnesium, remains normal.[5]
Treatment
Many medications are available that vary in efficacy, drug toxicity, and costs.[6]Due to the narrow therapeutic window of these medications, generic substitution should be done carefully according to a clinical practice guideline.[7]
Monitoring of drug levels may help.[8]
Levetiracetam was approved in the United States of America November 30, 1999[9] and the European Union September, 2000[10] and so was not included in the SANAD randomized controlled trial which started randomizing patients on Dec 1, 1999.[11][12][13]
Generalised epilepsy
For idiopathic generalised epilepsy or difficult to classify epilepsy, the SANAD randomized controlled trial compared valproate, lamotrigine, or topiramate and concluded:[11][12]
- "valproate remains the clinically most effective drug, although topiramate may be a cost-effective alternative for some patients".
- Regarding drug toxicity
- lamotrigine had more hypersensitivity (allergic) reactions
- valproate had more weight gain
- topiramate had more fatigue, behavioral changes, problems and weight loss
Partial epilepsy
For partial epilepsy, the SANAD randomized controlled trial compared carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate and concluded:[13]
- lamotrigine had similar efficacy to carbamazepine
- lamotrigine had less drug toxicity than carbamazepine
A separate randomized controlled trial compared levetiracetam to carbamazepine while drug toxicity is lower for levetiracetam than carbamazepine.[14]
Lamotrigine and levetiracetam have not been compared as of June, 2008.
Prognosis
After a first seizure, the likelihood of a second seizure within three years is 29%[15][16] to 78%[17].
References
- ↑ Epilepsy. MedlinePlus, U.S. National Library of Medicine and National Institutes of Health.
- ↑ Ropper, Allan H.; Adams, Raymond Delacy; Victor, Maurice (1997). Principles of Neurology (in English), 6th. New York: McGraw-Hill, Health Professions Division, 313. ISBN 0-07-067439-6.
- ↑ National Library of Medicine. Epilepsy. Retrieved on 2008-05-23.
- ↑ Hippocrates. (400 BCE). On the Sacred Disease. Translated by Francis Adams.
- ↑ Sinert R, Zehtabchi S, Desai S, Peacock P, Altura BT, Altura BM (2007). "Serum ionized magnesium and calcium levels in adult patients with seizures". Scand. J. Clin. Lab. Invest. 67 (3): 317–26. DOI:10.1080/00365510601051441. PMID 17454846. Research Blogging.
- ↑ (June 2008) "Drugs for epilepsy". Treat Guidel Med Lett 6 (70): 37–46. PMID 18497720. [e]
- ↑ Liow K, Barkley GL, Pollard JR, Harden CL, Bazil CW (April 2007). "Position statement on the coverage of anticonvulsant drugs for the treatment of epilepsy". Neurology 68 (16): 1249–50. DOI:10.1212/01.wnl.0000259400.30539.cc. PMID 17438213. Research Blogging.
- ↑ Johannessen SI, Battino D, Berry DJ, Bialer M, Krämer G, Tomson T et al. (2003). "Therapeutic drug monitoring of the newer antiepileptic drugs.". Ther Drug Monit 25 (3): 347-63. PMID 12766564. [e]
- ↑ Anonymous (1999). Drugs@FDA. Food and Drug Administration.
- ↑ 11.0 11.1 Marson AG, Al-Kharusi AM, Alwaidh M, et al (2007). "The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial". Lancet 369 (9566): 1016–26. DOI:10.1016/S0140-6736(07)60461-9. PMID 17382828. Research Blogging. ACP Journal Club summary
- ↑ 12.0 12.1 Marson AG, Appleton R, Baker GA, et al (2007). "A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial". Health technology assessment (Winchester, England) 11 (37): 1–154. PMID 17903391. [e]
- ↑ 13.0 13.1 Marson AG, Al-Kharusi AM, Alwaidh M, et al (March 2007). "The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial". Lancet 369 (9566): 1000–15. DOI:10.1016/S0140-6736(07)60460-7. PMID 17382827. PMC 2080688. Research Blogging.
- ↑ Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ (February 2007). "Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy". Neurology 68 (6): 402–8. DOI:10.1212/01.wnl.0000252941.50833.4a. PMID 17283312. Research Blogging.
- ↑ Hauser WA, Rich SS, Annegers JF, Anderson VE (August 1990). "Seizure recurrence after a 1st unprovoked seizure: an extended follow-up". Neurology 40 (8): 1163–70. PMID 2381523. [e]
- ↑ Kim LG, Johnson TL, Marson AG, Chadwick DW (April 2006). "Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial". Lancet Neurol 5 (4): 317–22. DOI:10.1016/S1474-4422(06)70383-0. PMID 16545748. Research Blogging.
- ↑ Hart YM, Sander JW, Johnson AL, Shorvon SD (November 1990). "National General Practice Study of Epilepsy: recurrence after a first seizure". Lancet 336 (8726): 1271–4. PMID 1978114. [e]