Seizures in Adults: Impact on Social Interactions and Functional Abilities

The incidence rate of a single unprovoked seizure in adults is 23 to 61 cases/100,000 person-years. A seizure can substantially affect a person’s social interactions, employment, and driving eligibility.

After a first unprovoked seizure, the overall risk of recurrence can be as high as 60%, and this risk is highest within the first 2 years.

Epilepsy affects 0.65% of adults worldwide. This incidence is higher in developing countries.

Epilepsy is diagnosed after 2 unprovoked seizures that occur more than 24 hours apart or after a single event that occurs in a person considered to be at high risk of recurrence (>60% risk over a 10-hour period) . years).

Abnormal electroencephalogram (EEG) findings, abnormal neurological status, and a second seizure increase the likelihood of seizure recurrence. These three factors allow risk to be stratified into low, medium and high, and help guide initial therapeutic decisions, with anticonvulsants.

Occasionally, serial seizures or status epilepticus manifest as a first seizure, and these conditions can be life-threatening.

> Diagnosis and evaluation

Knowing the history obtained by experts is essential for the diagnosis of an epileptic seizure. Telephoning a witness is often invaluable, and home videos of patients with frequent seizures can help with diagnosis.

Provoked seizures may occur following a transient cerebral insult, such as alcohol withdrawal, use of illicit drugs such as cocaine and methamphetamine, and metabolic disturbances (e.g., hypoglycemia, hyponatremia). They may also suggest a structural cause such as hemorrhagic stroke, encephalitis, venous sinus thrombosis, or tumor.

Seizures and epilepsy are classified according to the type of seizure (generalized, focal, or unknown), type of epilepsy, and epilepsy syndrome.

The presentation of a seizure depends on its site of onset (generalized or focal) and pattern of spread. Seizures can occur at any age and in any situation. In some cases, lack of warning suggests generalized onset, although lack of warning is also consistent with focal onset seizures, especially in the frontal lobe.

In other cases (usually seizures of focal onset), there is a specific, but often "indescribable" aura, such as déjà vu , an epigastric or "rising" sensation, tastes or smells, usually followed by transient alteration of consciousness.

A convulsive seizure usually has a tonic (rigidity) and a clonic (convulsive) phase.

Together, these phases last 1 to 3 minutes, while the patient has eyes open, apnea, and cyanosis. Patients wake up many minutes later and feel tired and sore; sometimes they have a lateral bite of the tongue.

The physical examination may reveal signs that point to a cause other than a seizure or a condition that predisposes to seizures.

Attention should be paid to examination of the skin (e.g., presence of facial angiofibromas, hypomelanotic macules suggestive of tuberous sclerosis, or self-injury scars often associated with non-epileptic psychogenic seizures), the cardiovascular system (an aortic ejection murmur may indicate cardiac syncope and postural changes in blood pressure may indicate orthostatic hypotension) and fundus findings (e.g., intracranial hypertension).

Basic blood tests should be ordered to measure levels of electrolytes, glucose, calcium, and magnesium, to identify possible causes of seizures or coexisting conditions.

Electrocardiogram (ECG) is indicated in all patients (especially older adults) who have had a first seizure or unexplained fainting, to look for evidence of previous myocardial infarction, due to the risk of ventricular tachycardia or a rare but potentially fatal disorder . (and often familial), including hypertrophic cardiomyopathy and long QT syndrome.

> Brain imaging

In patients who present a first epileptic seizure, urgent brain imaging should be requested.

CT scan is useful and widely available. However, in most adults with a first seizure (especially a focal-onset seizure) or early epilepsy, magnetic resonance imaging (MRI) shows detailed images, especially 3T-MRI with a slice thickness <3 mm on T2-weighted and fluid-attenuated inversion recovery images).

More subtle underlying causes such as hippocampal sclerosis, focal cortical dysplasia, or a surgical candidate tumor can be identified using MRI.

> Electroencephalography

Interictal EEG, which is performed in patients who have had a first seizure, is unlikely to capture another seizure, although the procedure may cause psychogenic nonepileptic seizures.

EEG is more informative in patients <25 years of age because they are more likely to have generalized interictal subclinical activity, which can confirm a generalized seizure and a strong tendency for new seizures (70% positive predictive value).

EEG performed shortly after a first seizure identifies more epileptiform abnormalities than subsequent EEG.

EEG performed in ambulatory or sleep-deprived patients increases diagnostic yield even more than in patients in whom an epileptic seizure is likely despite routine interictal EEG findings being normal.

The presence of interictal epileptiform discharges in any of these investigations increases the risk of seizure recurrence 1.5 times 1 year later.

> Anti-seizure medications

Medical treatment of epilepsy involves suppression of seizures through the long-term use of oral medication.

These medications are primarily indicated when the risk of new spontaneous seizures is estimated to exceed 60% over the next 10 years.

The therapeutic goal is the absence of seizures, with minimal adverse effects. However, if it is impossible to achieve these goals, the priority is complete control of major seizures, which are potentially dangerous because they can increase the risk of sudden unexpected death in epilepsy, above the absolute risk of death among patients. with epilepsy in general (1.2 cases/1,000 patient-years).

Initiating long-term anticonvulsants is an important decision for both the patient and the physician. This decision requires a reasonably certain diagnosis of epilepsy. In patients with an uncertain diagnosis, the use of medications should be avoided for a trial period.

A major trial showed that the risk of seizure recurrence in early epilepsy and single seizures was lowest in the first 2 years after the first seizure in patients who started treatment immediately (usually carbamazepine or sodium valproate). ) than those who received delayed treatment, waiting for a second seizure (32% vs. 39%), but earlier initiation of treatment did not affect longer-term seizure remission.

Adverse events were significantly more common with immediate treatment than with delayed treatment (39% and 31%). Quality of life measures were similar in the two groups. Therefore, doctors generally recommend not medicating patients who have had a single seizure unless the risk of recurrence is particularly high.

Despite the low estimated risk of recurrence, some patients choose to receive the medication because they have had a particularly severe illness or an injurious first seizure or because they live in areas where a second seizure could extend the driver’s license restriction.

> Factors that guide the choice of medications

The choice of medication should be guided by the type of seizure and epileptic syndrome. In general, valproate or levetiracetam is used in patients with generalized-onset seizures and lamotrigine or levetiracetam in those with focal-onset seizures), as well as for efficacy, adverse event profile, and pharmacodynamic and pharmacokinetic properties. Coexisting conditions must also be taken into account.

For example, for patients with substantial anxiety lamotrigine may be preferable to levetiracetam, while for those with obesity or migraines topiramate may be chosen, which may suppress appetite and reduce the incidence of headaches. A primary consideration for women is the potential effect of medication on pregnancy.

Sodium valproate administered during pregnancy carries great risks. Nearly 10% of babies exposed in utero to sodium valproate have major birth defects and up to 40% have neurodevelopmental delay.

In a European registry, 10.3% of infants are recorded with major congenital malformations after in utero exposure to valproate; in 5.5%, these malformations were observed after in utero exposure to carbamazepine; in 3.9% they developed after exposure to topiramate; 3.0% after oxcarbazepine; 2.9% after lamotrigine and 2.8% after levetiracetam (compared with a risk of 2.6% in infants in the population who had not been exposed in utero to any anticonvulsant medication).

The possible contribution of maternal seizures to the risk of congenital anomalies and neurodevelopmental delay remains unclear. The EURAP study also showed that the major congenital malformations associated with valproate were dose-related and included heart defects and hypospadias, each of which were found in 2% of infants exposed to valproate; cleft lip; gastrointestinal, renal and neural tube defects and polydactyly.

Cognitive assessments in 6-year-old children who had been exposed in utero to valproate showed significant inverse associations with dose-dependent IQ, verbal ability, and nonverbal ability. These effects were not observed in children with in utero exposure to other anticonvulsants. Therefore, valproate should be avoided in women of childbearing potential.

If valproate is used, measures should be taken to prevent pregnancy unless the woman is fully informed about the risks. As part of a licensing requirement, since 2018, in the United Kingdom and European Union, women receiving valproate must use highly reliable contraceptives or undergo monthly pregnancy testing, and must sign a risk acknowledgment form annually.

Data from pregnancy registries have shown inconsistent safety signals for lamotrigine or levetiracetam, and there is no clear evidence of neurodevelopmental delay associated with these agents.

In observational studies, maternal folate supplementation has been associated with a decreased risk of neurocognitive abnormalities in infants with in utero exposure to antiseizure medications. This supplementation is routinely recommended for women who may become pregnant while receiving anticonvulsants.

> Medication effectiveness

A single-center observational study involving 525 patients with epilepsy of various types showed that almost half became seizure-free for at least 1 year after they started receiving a first antiseizure medication.

Many randomized, controlled trials of the efficacy of new anticonvulsants have evaluated their use as adjunctive medications in treatment-resistant epilepsy patients. In these short-term trials, these new medications reduced seizure frequency 2 to 4 times more than placebo, but often at doses that were higher than those commonly used.

The management of epilepsy, which is long-term, relies heavily on trials to establish the Standard for new antiepileptic drugs, which involved long-term use, making direct, unblinded comparisons of the drugs with newer existing standard agents. . The results of those trials show that the first-line medication for patients with generalized-onset seizures is sodium valproate, or levetiracetam for girls and women of childbearing potential.

For patients with focal-onset seizures, lamotrigine is usually the first-line medication, although levetiracetam or other agents may have advantages in some patients.

The main disadvantage of lamotrigine is its low initial dose, with increases to maximum doses over a period of several weeks. This gradual dose adjustment is necessary to reduce the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. For this reason, it seems justified to provide initial coverage with another anticonvulsant medication. The main adverse effects of levetiracetam are irritability and anxiety, especially in patients with pre-existing anxiety.

Doctors must make decisions jointly with their patients and share information, verbally and in writing. Information about driving eligibility is particularly important. The driving restriction varies in each country and depends on the patient’s condition (if they have had a single seizure with a low risk of recurrence, or they have a diagnosis of epilepsy and have experienced a single seizure, but with a high risk).

Doctors’ advice about other activities depends on the characteristics and frequency of the seizures. These factors must be balanced with individual priorities. Doctors should inform patients of the risks associated with seizures, including fainting and sudden death.

The likelihood of seizure recurrence and suggested lifestyle modifications (e.g., avoiding being alone during certain activities such as babysitting or bathing, so that another person can help if a seizure occurs, and appreciation of the risks of stairs and heights). Patients should be encouraged to adhere to the antiseizure medication regimen and maintain a regular sleep schedule, limiting alcohol use.

There is considerable observational data supporting a relationship between the risk of insufficient sleep and seizures or abnormal EEG activity. However, one trial found no relationship between seizures and sleep deprivation, although the author believes that these results may not be applicable to early epilepsy. Regardless, promoting sleep hygiene in patients with epilepsy remains prudent.

Alcohol consumption is an important precipitant of seizures, primarily due to the risk of seizures occurring during alcohol withdrawal.

Alcohol’s tendency to disrupt sleep may interfere with adherence to antiseizure medications. A meta-analysis of observational studies showed a dose-response relationship between the amount of alcohol consumed daily (average consumption of 4, 6, and 8 drinks daily) and the probability of developing epilepsy.

Abstinence from alcohol is probably unnecessary, but consumption should be limited to modest amounts. Illicit drugs that disrupt sleep, especially cocaine and amphetamine, should be avoided, but high-quality data on recreational cannabis use in people with epilepsy are lacking.

The clinical diagnosis of epilepsy may be incorrect in up to 20% of patients unless the episodes are captured on video EEG. Many patients diagnosed with epilepsy are later recognized as having psychogenic seizures, and psychogenic seizures may develop later in people with established epilepsy. Clinicians must repeatedly question the diagnosis in patients with drug-resistant epilepsy.

The possible long-term effects of a new anticonvulsant that is typically prescribed as a lifelong treatment warrants further study. Notably, vigabatrin was used worldwide within 8 years of being licensed to control seizures, until it was recognized that long-term use caused permanent visual field defects in more than half of patients.

Data are lacking on the outcomes of new anticonvulsants in pregnancy and offspring. It is recommended to inform pregnancy registries around the world of the teratogenic potential of anticonvulsants and update them periodically.

Genetic characterization has allowed the targeting of the most effective treatments for some complex epilepsies (e.g., stiripentol for Dravet syndrome and a ketogenic diet for transporter type 143 glucose deficiency syndrome) and the detection of the allele. HLA-B*1502 in Han Chinese populations, to predict carbamazepine-induced Stevens-Johnson syndrome).

It is necessary to expand knowledge about the effect of genetic factors on the risk of recurrent seizures, and about the effectiveness and risks of various medications, in order to guide therapeutic decisions.

In 2015, the American Academy of Neurology and the American Epilepsy Society provided guidelines on the management of an unprovoked first seizure in adults. The 2012 guidelines from the UK’s National Institute for Health and Care Excellence are under review. The current recommendations differ from these older guidelines regarding recommended medications, as the SANAD II trial results were published after these guidelines.