Adult epilepsy

doi:10.1016/S0140-6736(06)68477-8

The Lancet

Volume 367, Issue 9516, 1–7 April 2006, Pages 1087-1100

https://doi.org/10.1016/S0140-6736(06)68477-8 Get rights and content

Summary

The epilepsies are one of the most common serious brain disorders, can occur at all ages, and have many possible presentations and causes. Although incidence in childhood has fallen over the past three decades in developed countries, this reduction is matched by an increase in elderly people. Monogenic Mendelian epilepsies are rare. A clinical syndrome often has multiple possible genetic causes, and conversely, different mutations in one gene can lead to various epileptic syndromes. Most common epilepsies, however, are probably complex traits with environmental effects acting on inherited susceptibility, mediated by common variation in particular genes. Diagnosis of epilepsy remains clinical, and neurophysiological investigations assist with diagnosis of the syndrome. Brain imaging is making great progress in identifying the structural and functional causes and consequences of the epilepsies. Current antiepileptic drugs suppress seizures without influencing the underlying tendency to generate seizures, and are effective in 60–70% of individuals. Pharmacogenetic studies hold the promise of being able to better individualise treatment for each patient, with maximum possibility of benefit and minimum risk of adverse effects. For people with refractory focal epilepsy, neurosurgical resection offers the possibility of a life-changing cure. Potential new treatments include precise prediction of seizures and focal therapy with drug delivery, neural stimulation, and biological grafts.

Section snippets

Epidemiology

The incidence of epilepsy in developed countries is around 50 per 100 000 people per year, and is higher in infants and elderly people.7, 8, 9 Less wealthy people show a higher incidence, for unknown reasons.¹⁰ Poor sanitation, inadequate health delivery systems, and a higher risk of brain infections and infestations could contribute to a higher incidence—usually above 100 per 100 000 people per year—in resource-poor countries where most people with epilepsy usually do not receive treatment.8,

Pathophysiology

An epileptic seizure is a transient occurrence of signs, or symptoms, or both, due to abnormal excessive or synchronous neuronal activity in the brain.³⁸ Brief synchronous activity of a group of neurons leads to the interictal spike, which has a duration of less than 70 ms and is distinct from a seizure.³⁹ Indeed, the site of interictal spiking can be separate from the zone of seizure onset.

An early view that disruption of the normal balance between excitation and inhibition in the brain

Genetic basis and contribution

Genetic variation can determine the causes, susceptibility, mechanisms, syndrome, treatment response, prognosis, and consequences of the epilepsies to varying degrees. Part of the promise of genetics lies in its power to relate these characteristics of the overall clinical presentation of the individual patient. There has been considerable progress in this area.46, 47 Several monogenic Mendelian epilepsies are known, but are generally rare and account for few cases. There can be variation in

Diagnosis and investigation

The diagnosis of epilepsy remains clinical and is based on probability after assessment of the whole individual. Misdiagnosis is potentially very damaging. The differential diagnosis must therefore always be carefully considered. In some cases the diagnosis of epilepsy syndrome or seizure types is incorrect, or the events are not due to epilepsy at all, but instead have their basis in a cardiac, psychological, psychiatric, or metabolic disturbance. Such non-epileptic seizures are important to

Drug treatment

Antiepileptic drugs are the mainstay of epilepsy treatment. Non-pharmacological treatments are feasible only in a few selected cases and usually after antiepileptics have failed. Non-pharmacological options include curative surgery, palliative surgical procedures, and the ketogenic diet. The main indications for the ketogenic diet are severe forms of drug-resistant epilepsy in paediatric practice.94, 95 Overall, antiepileptic drugs are effective in 60–70% of individuals. The aim of

Surgery

In view of the rapidly diminishing chances of becoming seizure-free after trying three antiepileptic drugs,¹⁴³ individuals continuing to have focal seizures should have surgical treatment considered early on. The most common operations are temporal lobe resections, which are cost-effective procedures¹⁴⁴ carrying a 60–70% chance of making the individual seizure free145, 146 with improved quality of life.¹⁴⁷ The chance of a good outcome is greatest if the underlying cause is removed, driving

New treatment prospects

There remain difficulties in epilepsy treatment. Treatment should be individualised but remains empirical, and antiepileptic drugs fail for some patients. Despite the success of surgery in the treatment of such refractory focal epilepsy, it is suitable for less than 10% of these patients.¹⁵¹ Thus, new treatment strategies remain necessary.

Early prediction of seizures could have an enormous effect on the treatment of epilepsy, since it would allow action to be taken to prevent the seizure

Conclusions

The epilepsies are common, and heterogeneous by virtue of different seizure types, syndromes, causes, comorbidities, and other individual patient factors. Although up to 70% of patients will have their condition controlled with drugs, the remainder continue to have seizures and their negative effects on quality of life, morbidity, and risk of mortality. Surgical treatment is life-changing for a small proportion of patients. As genomics and proteomics unfold, the causation of epilepsies will

Search strategy and selection criteria

We searched PubMed for articles from 2002, with the keywords “epilep*”, “EEG”, “MRI”, “seizure prediction”, “SUDEP”, “antiepileptic drug”, “gene*”, “surgery”, and “mechanisms”. We also cite occasional earlier articles and reviews, where these are particularly relevant.

References (156)

AG Diop et al.
The global campaign against epilepsy in Africa
Acta Trop
(2003)
A Carpio
Neurocysticercosis: an update
Lancet Infect Dis
(2002)
HH Garcia et al.
Taenia solium cysticercosis
Lancet
(2003)
M Boussinesq et al.
Relationship between onchocerciasis and epilepsy: a matched case-control study in the Mbam Valley, Republic of Cameroon
Trans R Soc Trop Med Hyg
(2002)
L Nilsson et al.
Risk factors for sudden unexpected death in epilepsy: a case-control study
Lancet
(1999)
K Opeskin et al.
Risk factors for sudden unexpected death in epilepsy: a controlled prospective study based on coroners cases
Seizure
(2003)
FJ Rugg-Gunn et al.
Cardiac arrhythmias in focal epilepsy: a prospective long-term study
Lancet
(2004)
M de Curtis et al.
Interictal spikes in focal epileptogenesis
Prog Neurobiol
(2001)
LM Ward
Synchronous neural oscillations and cognitive processes
Trends Cogn Sci
(2003)
B Litt et al.
Prediction of epileptic seizures
Lancet Neurol
(2002)

J Engel

A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology

Epilepsia

(2001)

NICE

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care

HM De Boer

“Out of the shadows”: a global campaign against epilepsy

Epilepsia

(2002)

RA Scott et al.

The treatment of epilepsy in developing countries: where do we go from here?

Bull World Health Organ

(2001)

H Meinardi et al.

The treatment gap in epilepsy: the current situation and ways forward

Epilepsia

(2001)

BK MacDonald et al.

The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK

Brain

(2000)

JW Sander

The epidemiology of epilepsy revisited

Curr Opin Neurol

(2003)

L Forsgren et al.

The epidemiology of epilepsy in Europe—a systematic review

Eur J Neurol

(2005)

DC Heaney et al.

Socioeconomic variation in incidence of epilepsy: prospective community based study in south east England

BMJ

(2002)

JW Sander

(2001)

A Gaitatzis et al.

Life expectancy in people with newly diagnosed epilepsy

Brain

(2004)

A Gaitatzis et al.

The mortality of epilepsy revisited

Epileptic Disord

(2004)

J Hanna et al.

Death in the shadows: the national sentinel clinical audit into epilepsy death

(2002)

MR Sperling et al.

Seizure control and mortality in epilepsy

Ann Neurol

(1999)

Y Langan et al.

Case-control study of SUDEP

Neurology

(2005)

Cited by (678)

Robotic assessment of sensorimotor and cognitive deficits in patients with temporal lobe epilepsy
2024, Epilepsy and Behavior
Individuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening.
27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed.
Across the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment.
Our findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment.
Transient anticonvulsant effects of time-restricted feeding in the 6-Hz mouse model
2024, Epilepsy and Behavior
Intermittent fasting enhances neural bioenergetics, is neuroprotective, and elicits antioxidant effects in various animal models. There are conflicting findings on seizure protection, where intermittent fasting regimens often cause severe weight loss resembling starvation which is unsustainable long-term. Therefore, we tested whether a less intensive intermittent fasting regimen such as time-restricted feeding (TRF) may confer seizure protection.
Male CD1 mice were assigned to either ad libitum-fed control, continuous 8 h TRF, or 8 h TRF with weekend ad libitum food access (2:5 TRF) for one month. Body weight, food intake, and blood glucose levels were measured. Seizure thresholds were determined at various time points using 6-Hz and maximal electroshock seizure threshold (MEST) tests. Protein levels and mRNA expression of genes, enzyme activity related to glucose metabolism, as well as mitochondrial dynamics were assessed in the cortex and hippocampus. Markers of antioxidant defence were evaluated in the plasma, cortex, and liver.
Body weight gain was similar in the ad libitum-fed and TRF mouse groups. In both TRF regimens, blood glucose levels did not change between the fed and fasted state and were higher during fasting than in the ad libitum-fed groups. Mice in the TRF group had increased seizure thresholds in the 6-Hz test on day 15 and on day 19 in a second cohort of 2:5 TRF mice, but similar seizure thresholds at other time points compared to ad libitum-fed mice. Continuous TRF did not alter MEST seizure thresholds on day 28. Mice in the TRF group showed increased maximal activity of pyruvate dehydrogenase in the cortex, which was accompanied by increased protein levels of mitochondrial pyruvate carrier 1 in the cortex and hippocampus. There were no other major changes in protein or mRNA levels associated with energy metabolism and mitochondrial dynamics in the brain, nor markers of antioxidant defence in the brain, liver, or plasma.
Both continuous and 2:5 TRF regimens transiently increased seizure thresholds in the 6-Hz model at around 2 weeks, which coincided with stability of blood glucose levels during the fed and fasted periods. Our findings suggest that the lack of prolonged anticonvulsant effects in the acute electrical seizure models employed may be attributed to only modest metabolic and antioxidant adaptations found in the brain and liver. Our findings underscore the potential therapeutic value of TRF in managing seizure-related conditions.
Inhibition of PTEN-induced kinase 1 autophosphorylation may assist in preventing epileptogenesis induced by pentylenetetrazol
2024, Neurochemistry International
PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occurrence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague‒Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis.
Analysis of the global burden of disease study highlights the global, regional, and national trends of idiopathic epilepsy epidemiology from 1990 to 2019
2023, Preventive Medicine Reports
Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study.
In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions.
Adult epilepsy
2023, The Lancet
Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.
The Apelin/APJ system modulates seizure activity and endocytosis of the NMDA receptor GluN2B subunit
2023, Neurochemistry International
In the central nervous system (CNS), the apelin/APJ system is broadly expressed. According to some studies, activation of this system protects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors and exerts neuroprotective effects. However, the role of this system in epilepsy remains unclear. In the present study, immunofluorescence staining and western blotting were used to assess APJ localization and expression in the brains of mice with recurrent spontaneous seizures induced by kainic acid (KA). Behavior and local field potentials (LFPs) were assessed in mice with KA-induced seizures. Susceptibility to seizures was assessed in a pentylenetetrazole (PTZ)-induced seizure model. Whole-cell patch-clamp recordings were used to evaluate the role of the apelin/APJ system in regulating synaptic transmission in brain slices from mice in which Mg²⁺-free medium was used to induce seizures. NMDA receptor GluN2B subunit expression and phosphorylation of GluN2B at Ser1480 were measured in the mouse hippocampus. APJ was primarily localized in neurons, and its expression was upregulated in the epileptic brain. APJ activation after KA-induced status epilepticus (SE) reduced epileptic activity, whereas APJ inhibition aggravated epileptic activity. In the PTZ model, APJ activation reduced and APJ inhibition increased susceptibility to seizures. The apelin/APJ system affected NMDA receptor-mediated postsynaptic currents in patch-clamp recordings. Moreover, APJ regulated the levels of GluN2B phosphorylated at Ser1480 and the abundance of cell-surface GluN2B in neurons. Furthermore, endocytosis of the NMDA receptor GluN2B subunit was regulated by the apelin/APJ system. Together, our findings indicate that the apelin/APJ system modulates seizure activity and may be a novel therapeutic target for epilepsy.

View all citing articles on Scopus

View full text

SeminarAdult epilepsy

Summary

Section snippets

Epidemiology

Pathophysiology

Genetic basis and contribution

Diagnosis and investigation

Drug treatment

Surgery

New treatment prospects

Conclusions

Search strategy and selection criteria

Acta Trop

Lancet Infect Dis

Lancet

Trans R Soc Trop Med Hyg

Lancet

Seizure

Lancet

Prog Neurobiol

Trends Cogn Sci

Lancet Neurol

Am J Hum Genet

J Am Coll Cardiol

Neuroimage

Neuroimage

Neuroimage

Neuroimage

Neuroimage

Neuroimage

Semin Pediatr Neurol

Lancet Neurol

A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology

Epilepsia

The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care

“Out of the shadows”: a global campaign against epilepsy

Epilepsia

The treatment of epilepsy in developing countries: where do we go from here?

Bull World Health Organ

The treatment gap in epilepsy: the current situation and ways forward

Epilepsia

The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK

Brain

The epidemiology of epilepsy revisited

Curr Opin Neurol

The epidemiology of epilepsy in Europe—a systematic review

Eur J Neurol

Socioeconomic variation in incidence of epilepsy: prospective community based study in south east England

BMJ

Infectious agents and epilepsy

Incidence of epilepsy is now higher in elderly people than children

BMJ

Reducing mortality: an important aim of epilepsy management

J Neurol Neurosurg Psychiatry

Epilepsy and mortality: a record linkage study in a U.K. population

Epilepsia

First epileptic seizure in the elderly: electroclinical and etiological data in 341 patients

Rev Neurol (Paris)

Tapeworms and seizures—treatment and prevention

N Engl J Med

Increased prevalence of epilepsy associated with severe falciparum malaria in children

Epilepsia

Prevalence, incidence, and etiology of epilepsies in rural Honduras: the Salama Study

Epilepsia

Epilepsy, cysticercosis, and toxocariasis: a population-based case-control study in rural Bolivia

Neurology

Factors predicting prognosis of epilepsy after presentation with seizures

Ann Neurol

Staged approach to epilepsy management

Neurology

Response to first drug trial predicts outcome in childhood temporal lobe epilepsy

Neurology

The natural history of epilepsy: an epidemiological view

J Neurol Neurosurg Psychiatry

The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic

QJM

The epidemiology of the comorbidity of epilepsy in the general population

Epilepsia

Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort

Ann Neurol

Seminar
Adult epilepsy