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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

Epilepsies are common disorders of the central nervous system (CNS), affecting up to 2% of the global population.

Fiest et al., searched MEDLINE and EMBASE for articles published on the prevalence or incidence of epilepsy since 1985. Abstract, full-text review, and data abstraction were conducted in duplicate. Meta-analyses and meta-regressions were used to explore the association between prevalence or incidence, age group, sex, country level income, and study quality.

A total of 222 studies were included (197 on prevalence, 48 on incidence). The point prevalence of active epilepsy was 6.38 per 1,000 persons (95% confidence interval [95% CI] 5.57-7.30), while the lifetime prevalence was 7.60 per 1,000 persons (95% CI 6.17-9.38). The annual cumulative incidence of epilepsy was 67.77 per 100,000 persons (95% CI 56.69-81.03) while the incidence rate was 61.44 per 100,000 person-years (95% CI 50.75-74.38). The prevalence of epilepsy did not differ by age group, sex, or study quality. The active annual period prevalence, lifetime prevalence, and incidence rate of epilepsy were higher in low to middle income countries. Epilepsies of unknown etiology and those with generalized seizures had the highest prevalence.

This study provides a comprehensive synthesis of the prevalence and incidence of epilepsy from published international studies and offers insight into factors that contribute to heterogeneity between estimates. Significant gaps (e.g., lack of incidence studies, stratification by age groups) were identified. Standardized reporting of future epidemiologic studies of epilepsy is needed 1).

Classification

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

Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low grade glioma and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment 3).

Treatment

Elucidating the mechanism of selective regulation of different aquaporins (AQPs) and associated regulatory proteins may provide a new therapeutic approach to epilepsy treatment 4).

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome.

Most patients will respond to one or two different medication trials. The goal of this treatment is the elimination of seizures, since uncontrolled seizures carry significant risks, including injury and sudden death. However, in up to one third of patients with epilepsy, medications alone will be unable to eliminate seizures, or cause unacceptable adverse effects. In these patients, work up for the feasibility of epilepsy surgery is considered.

see epilepsy surgery.

Neurostimulation technologies and neurosurgical procedures have improved the clinical outcomes of patients with epilepsy, and have led to important advances in understanding the neuropathophysiology of epilepsy/seizures and brain plasticity. For example, neurostimulation allows long-term in vivo electroneurophysiological recordings of specific brain regions that has not been previously possible in humans 5).

Outcome

Young adults with epilepsy are particularly susceptible to behavioral health and neurodevelopmental disorders 6).

Most patients respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures despite multiple antiepileptic drugs.

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 7).

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 8).

1)
Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, Pringsheim T, Lorenzetti DL, Jetté N. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology. 2016 Dec 16. pii: 10.1212/WNL.0000000000003509. [Epub ahead of print] PubMed PMID: 27986877.
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)
Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD. Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014. doi: 10.1016/B978-0-444-53486-6.00051-X. PubMed PMID: 27430454.
4)
Salman MM, Sheilabi MA, Bhattacharyya D, Kitchen P, Conner AC, Bill RM, Woodroofe MN, Conner MT, Princivalle AP. Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy. Eur J Neurosci. 2017 Jul 17. doi: 10.1111/ejn.13652. [Epub ahead of print] PubMed PMID: 28715131.
5)
Schoenberg MR, Frontera AT, Bozorg A, Hernandez-Frau P, Vale F, Benbadis SR. An update on epilepsy. Expert Rev Neurother. 2011 May;11(5):639-45. doi: 10.1586/ern.11.50. PubMed PMID: 21539485.
6)
Wagner JL, Wilson DA, Kellermann T, Smith G, Malek AM, Wannamaker B, Selassie AW. Behavioral health in young adults with epilepsy: Implications for transition of care. Epilepsy Behav. 2016 Nov 6;65:7-12. doi: 10.1016/j.yebeh.2016.09.028. [Epub ahead of print] PubMed PMID: 27829187.
7)
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.
8)
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: 2017/07/18 11:57 by administrador