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epilepsy

Epilepsy

Epilepsy is characterized by unpredictable and sudden paroxysmal neuronal firing occurrences and sometimes evolving in clinically evident seizure.

Epilepsy is associated with disruption of integration in distributed networks, together with altered localization for functions such as expressive language. The relation between atypical network connectivity and altered localization is unknown.

These seizures are episodes that can vary from brief and nearly undetectable to long periods of vigorous shaking.

In epilepsy, seizures tend to recur, and have no immediate underlying cause while seizures that occur due to a specific cause are not deemed to represent epilepsy.

There is a critical need for new drugs and approaches given than at least one-third of all epilepsy patients are not made free of seizures by existing medications and become “medically refractory”.

Findings indicate a critical contribution of astrocytes, star-shaped glial cells in the brain, to neuronal and network excitability and seizure activity. Furthermore, many important cellular and molecular changes occur in astrocytes in epileptic tissue in both humans and animal models of epilepsy.

Epidemiology

Classification

see Epilepsy classification.

Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies 1).

Etiology

Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target Messenger RNA.

Clinical features

People with epilepsy experience headaches irrespective of their sex or age. The burden of headaches is very important in patients with epilepsy, since headaches usually cause a moderate or severe burden to their quality of life and suggest a clear clinical need. Clinicians should recognize headache as a common comorbidity of epilepsy, as it may influence antiepileptic drug choice, and may need specific treatment 2).

Diagnosis

Treatment

Outcome

Is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas. The presence of seizures in patients with brain tumors implies favorable and unfavorable factors. New-onset seizures represent an early warning sign for the presence of a brain tumor and count as a good prognostic factor for survival. Recurrence or worsening of seizures during the course of disease may signal tumor progression. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic drugs (AEDs) and may severely impair the burden of living with a brain tumor. For symptomatic therapy of BTE, seizure type and individual patient factors determine the appropriate AED. Randomized controlled trials in partial epilepsy in adults to which type BTE belongs and additional studies in gliomas indicate that levetiracetam is the agent of choice, followed by valproic acid (VPA). In the case of recurring seizures, combining these two drugs (polytherapy) seems effective and possibly synergistic. If either one is not effective or not well tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. A practice guideline on symptomatic medical management including dose schedules of AEDs is supplied 3).

Case series

Kwan et al prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year.

Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent).

Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy 4).

1)
Devinsky O, Vezzani A, O'Brien TJ, Jette N, Scheffer IE, de Curtis M, Perucca P. Epilepsy. Nat Rev Dis Primers. 2018 May 3;4:18024. doi: 10.1038/nrdp.2018.24. Review. PubMed PMID: 29722352.
2)
Mameniškienė R, Karmonaitė I, Zagorskis R. The burden of headache in people with epilepsy. Seizure. 2016 Aug 5;41:120-126. doi: 10.1016/j.seizure.2016.07.018. [Epub ahead of print] PubMed PMID: 27543963.
3)
Vecht CJ, Kerkhof M, Duran-Pena A. Seizure Prognosis in Brain Tumors: New Insights and Evidence-Based Management. Oncologist. 2014 Jun 4. pii: theoncologist.2014-0060. [Epub ahead of print] Review. PubMed PMID: 24899645.
4)
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. PubMed PMID: 10660394.
epilepsy.txt · Last modified: 2018/05/12 19:05 by administrador