Search

To investigate the opinions of physicians about brain surgery for drug-resistant epilepsy worldwide.Practicing neurologists, psychiatrists, and neurosurgeons from around the world were invited to participate in an online survey. The survey anonymously collected data about demographics, years in clinical practice, discipline, nation, work setting, and answers to the questions about beliefs and attitudes about brain surgery for drug-resistant epilepsy.In total, 1410 physicians from 20 countries and different world regions participated. The propensity to discuss brain surgery with patients, who have drug-resistant seizures, was higher among men (versus women) [Odds Ratio (OR) 1.67, 95% CI 1.20-2.31; p = 0.002]. In comparison to neurologists, psychiatrists were less likely (OR 0.28, 95% CI 0.17-0.47; p 0.001) and neurosurgeons were more likely (OR 2.00, 95% CI 1.08-3.72; p = 0.028) to discuss about it. Survey participants working in Africa, Asia, the Middle East, and the Former Union of Soviet Socialist Republics showed a lower propensity to discuss epilepsy surgery with patients.This study showed that on an international level, there is still a knowledge gap concerning epilepsy surgery and much needs to be done to identify and overcome barriers to epilepsy surgery for patients with drug-resistant seizures worldwide.

Major disruption in the delivery of healthcare services can occur in exceptional situations such as natural disasters, conflicts, periods of severe economic hardship, and epidemics. These disruptions typically affect to the greatest extent the most vulnerable segments of the population, including people with epilepsy. Inability to access healthcare services can lead to failure to undergo necessary diagnostic investigations, or to receive needed therapeutic interventions, including epilepsy surgery. Stress and other factors associated with the nature or the cause of the disruption can adversely affect seizure control status, or precipitate the occurrence of psychiatric disorders and other comorbid conditions. Failure to access antiseizure medications is a common occurrence in these situations and can result in loss of seizure control, withdrawal seizures, and status epilepticus. In this article, we provide examples of recent disruptions in healthcare and their implications for people with epilepsy. We discuss the consequences of natural disasters, conflicts, economic sanctions, and focus in greater detail on lessons learnt during the COVID-19 pandemic. We also discuss possible mitigation procedures, focusing in particular on the application of telemedicine to epilepsy care. Finally, we underline the need for governments, healthcare authorities, and international organizations to improve their preparedness to deal with exceptional situations that may arise in the future.

In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains), management of people with epilepsy with available ASMs can be difficult. A group of experts was brought together by the International League Against Epilepsy (ILAE) to formulate recommendations for such circumstances. Every effort was made to base these recommendations on direct published literature or extrapolations from basic information available about ASMs. Actual published literature in this area is, however, limited, and at times, assumptions were made by the experts to generate these recommendations. During times of shortage of ASMs, switching between different ASMs (e.g., oxcarbazepine and carbamazepine) can occasionally be considered as a mitigation procedure. However, for many ASMs, the option of an overnight switch to another drug does not exist. Switching from brand to generic or between generic products has often been shown to be safe, if required. Finally, when supplies of benzodiazepines or equipment to administer medications intravenously are not available, rectal administration of some ASMs may be an emergency alternative route for treating serial seizures and status epilepticus. Decision-making with regard to treatment and possible options should be driven by what is best for the patient.

The aim of the current study was to investigate the age at onset in patients with Lennox-Gastaut Syndrome (LGS). We also investigated the clinical and EEG characteristics of these patients in different age groups. This was a retrospective study. All patients with a diagnosis of LGS were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 through 2020. 300 patients had LGS. Age at onset was 3.3 ± 4.1 years (minimum = 0 and maximum = 21 years). In 10 patients (3%) LGS started at age 14 years or above. Epileptic spasms were more often observed in those with an age at onset below one year (8%) compared with those with an age at onset of 1 to 8 years (0.7%) [Odds Ratio (OR) = 10.32]. Intellectual disability was less frequently observed in those with an age at onset of 8 years and above (68%) compared with those with an age at onset of 1 to 8 years (90%) (OR = 0.33). Tonic-clonic seizures were more often observed in those with an age at onset of 8 years and above (83%) compared with those with an age at onset of 1 to 8 years (55%) (OR = 2.87). While age at onset of LGS in the majority of patients is below 8 years, in some patients the syndrome begins in their late childhood or even during adolescence. Age at onset of LGS has significant correlations with the clinical manifestations of the syndrome.

The aim of the current study was to investigate the seizure outcome and also factors associated with that in patients with epilepsy [i.e., idiopathic generalized epilepsies (IGEs), symptomatic generalized epilepsies (SGEs), and focal epilepsies], who received either lamotrigine (LTG) or levetiracetam (LEV). This was a retrospective longitudinal study. All patients with a diagnosis of IGE, focal epilepsy, or SGE, who received either LTG or LEV, were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran from 2008 until 2020. All patients had to be followed at our center for at least 14 months. Two hundred and thirty-six patients were studied (101 IGE, 98 focal epilepsy, and 37 SGE). At the first visit, LTG was prescribed for 159 patients; 40 people (25.2%) became seizure-free, and LEV was prescribed for 77 people; 23 persons (29.9%) became seizure-free (p = 0.438). Patients who were not taking any drug at the time of their first visit, or were receiving fewer drugs, and those who had received fewer drugs in their drug history were more likely to enjoy a seizure-free state at the follow-up. Among the patients, who received LTG at the first visit, taking any Na-channel blocking drug (e.g., carbamazepine) in the drug history was associated with a poor seizure outcome; this was not the case for LEV. Implementation of appropriate personalized treatment plans in patients with epilepsy is of paramount significance. Rational selection of appropriate drug(s) is the mainstay of this process.

Background: We investigated the longevity of COVID-associated brain fog in patients who have survived the COVID-19. Methods: This was a follow-up study of 2,696 adult patients with COVID-19 from our previous study (doi: 10.1002/jmv.27404). We selected every other patient in our database. The follow-up data were collected during a phone call to the participants in January-February 2022 (11 months after the initial study): concentration difficulty and the patient’s self-declared status in their ability to concentrate. Results: In total, 1164 people were included; 35 people (3.0%) had concentration difficulty and 65 individuals (5.6%) had a worsened status in their ability to concentrate and think; 26 people (2.2%) responded yes to both questions and were considered as having long-lasting brain fog. People with long-lasting brain fog were more often admitted to ICUs during the initial hospitalization (23.1% vs. 9.3%; p = 0.032) compared with those without long-lasting brain fog. Conclusion: We may conclude that a minority of the hospitalized patients with COVID-19 may suffer from long-lasting post-COVID brain fog, at least for more than one year after their initial illness. Long-lasting post-COVID brain fog has a significant association with the severity of the initial illness.

To investigate the seizure outcome and factors associated with that in patients with newly diagnosed epilepsy, based on a syndromic approach [i.e. idiopathic generalized epilepsies (IGEs)This was a retrospective longitudinal study of a prospectively developed database. All newly-diagnoses patients with a diagnosis of IGE, focal epilepsy, SGE, or unclassified epilepsy, who received treatment from 2008 until 2018, were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran. All patients had to be followed at our center for at least 14 months.Four hundred and ten patients were studied [208 people with focal epilepsy (50.7%), 130 with IGE (31.7%), 49 with SGE (12%), and 23 patients with unclassified epilepsy (5.6%)]. Overall, 216 (52.7%) individuals became seizure-free for at least one year after their first therapeutic plan. The second therapeutic attempt in patients, who did not achieve seizure freedom with the first treatment plan, yielded seizure-free outcome in 52 patients (28.7%). The odds ratio of drug-resistance in patients with focal epilepsy compared with that in those with IGE was 1.816 (95% CI: 1.039-3.171; p = 0.036). The odds ratio of drug-resistance in patients with SGE compared with that in those with IGE was 8.543 (95% CI: 3.993-18.274; p = 0.0001).Implementation of appropriate personalized treatment plans in PWE is of paramount significance and the primary step towards such a strategy is to making a syndromic diagnosis of the condition.

AIM Psychogenic nonepileptic seizures (PNES) or functional seizures are universal phenomena. However, data on their epidemiology is limited. The aim of the current study was to review the literature on the epidemiology of PNES and to provide analytical estimates of its incidence and prevalence based on the direct data that are available from previous studies on PNES. METHODS The methods of this work had two parts: (1) MEDLINE, PsycINFO, and Scopus from inception to 19 October 2019 were systematically searched. (2) The analytical study of the incidence and prevalence of PNES was performed, based on the following data from previous studies: incidence of PNES, duration of PNES before making a diagnosis, outcome and mortality of PNES. RESULTS The search strategy yielded five articles; three were on the incidence and two on the prevalence. In the analytical part of the study, the incidence of PNES was calculated to be 3.1 (95% Confidence Interval: 1.1-5.1) per 100,000 population per year. The calculated prevalence rate of PNES in 2019 was 108.5 (95% Confidence Interval: 39.2-177.8) per 100,000 population, in the USA. CONCLUSION While, the generalizability of these calculated incidence and prevalence rates to other places in the world is limited, they give us a reasonable hint that PNES is a common condition and the prevalence is much more than that it was thought before.Supplemental data for this article is available online at https://doi.org/10.1080/00207454.2021.1942870.

Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery.We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls.Nine centers from 3 continents contributed 206 patients operated for drug-resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss-of-function (LoF) variants (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.9-3.5, p = 1.3E-09) and in genes encoding voltage-gated cation channels (OR = 2.4, 95% CI = 1.4-3.8, p = 2.7E-04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between-group differences.Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision-making and counseling. ANN NEUROL 2022.

The aim of this systematic review was to provide the required information regarding different aspects of the relationship between epilepsy/antiseizure medications and non-alcoholic drinks. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were followed. MEDLINE and Scopus from the inception until 7 August 2021 were systematically searched. These key words were used: "epilepsy" OR "seizure" OR "antiepileptic" OR "antiseizure" OR "anticonvulsant" AND "coffee" OR "tea" OR "soda" OR "juice" OR "drink" OR "cola" OR "diet" (35 key word combinations). The primary search yielded 21 458 publications (PubMed, n = 4778; Scopus, n = 16 680). Only 50 studies met all the inclusion criteria and were included in the current systematic review. In total, 17 articles investigated various non-alcoholic drinks in human studies, 11 studies were case reports/series, and 22 articles were animal/in vitro studies. None of the studies provided a class 1 of evidence. There is limited evidence suggesting that certain drinks (eg, caffeinated energy drinks) might trigger seizures. Patients with epilepsy should avoid excessive consumption of certain fruit juices (eg, grapefruit, lime, pomegranate, kinnow, and star fruit) and caffeinated drinks. However, daily coffee and tea intake can be part of a healthy balanced diet, and their consumption does not need to be stopped in patients with epilepsy. Coffee/tea consumption is not harmful if consumed at levels of 200 mg (caffeine) in one sitting (about 2½ cups of coffee) or 400 mg daily (about five cups of coffee).

The coronavirus disease 2019 (COVID‐19) pandemic has affected the care of all patients around the world. The International League Against Epilepsy (ILAE) COVID‐19 and Telemedicine Task Forces examined, through surveys to people with epilepsy (PWE), caregivers, and health care professionals, how the pandemic has affected the well‐being, care, and services for PWE. The ILAE included a link on their website whereby PWE and/or their caregivers could fill out a survey (in 11 languages) about the impact of the COVID‐19 pandemic, including access to health services and impact on mental health, including the 6‐item Kessler Psychological Distress Scale. An anonymous link was also provided whereby health care providers could report cases of new‐onset seizures or an exacerbation of seizures in the context of COVID‐19. Finally, a separate questionnaire aimed at exploring the utilization of telehealth by health care professionals since the pandemic began was available on the ILAE website and also disseminated to its members. Seventeen case reports were received; data were limited and therefore no firm conclusions could be drawn. Of 590 respondents to the well‐being survey (422 PWE, 166 caregivers), 22.8% PWE and 27.5% caregivers reported an increase in seizure frequency, with difficulty in accessing medication and health care professionals reported as barriers to care. Of all respondents, 57.1% PWE and 21.5% caregivers had severe psychological distress (k score >13), which was significantly higher among PWE than caregivers (p

We hypothesized that the international economic sanctions have affected various groups of Iranian people and have compromised their right to access medicines.Scopus and MEDLINE from their inception to 15 May 2022 were systematically searched for related published original manuscripts. The following keywords were used (title/abstract): "sanction(s)" AND "Iran". The inclusion criteria were all human studies and articles written in English.We could identify 24 articles. Sanctions have severely restricted patients with thalassemia, haemophilia, epilepsy, and multiple sclerosis from receiving their medical needs. Surveys and interviews of patients, healthcare professionals, and policy-makers have repeatedly shown that sanctions have greatly affected the health system in Iran.International economic sanctions have limited access of the Iranian people to medicines and are associated with the suffering of Iranians. This situation should provide a lesson for policymakers in other similar instances worldwide.

This survey aimed to investigate the opinions of the parents of children with epilepsy with regard to the application of epilepsy surgery for their children.We surveyed all the parents of children with epilepsy referred to our neurology clinic (Shiraz University of Medical Sciences) in April-July 2022. We collected their opinions about epilepsy surgery based on a predesigned questionnaire. The inclusion criteria included parents of all children with epilepsy (1 to 16 years of age, with at least one-year history of epilepsy, and with at least one drug used in the past 12 months).In total, 472 people participated in the study; 277 participants (58.7%) were willing to have epilepsy surgery for their child; the most common reason was to be able to discontinue the drugs. Sex (male), age (younger), and education (college) of the parents had significant associations with the parental willingness to have surgery for their children. The patient's drug regimen (polytherapy) and history of ictal injury (in the child) also had significant associations with the parental willingness to have surgery for the children.Most parents of children with epilepsy are willing to have epilepsy surgery for their children if their physician presents epilepsy surgery to them as an established, safe, and effective treatment option. Patient and parental-related factors should be considered when designing educational materials and programs for preoperative counseling for the parents of children with drug-resistant seizures.

We tried to differentiate childhood absence epilepsy (CAE) from juvenile absence epilepsy (JAE) based on their clinical characteristics. We planned to identify a cutoff point for the age at onset of seizures between CAE and JAE that is able to reliably predict the presence of generalized tonic-clonic seizures (GTCS) (that has important implications for treatment strategy and outcome prediction).This was a retrospective database study. All patients with an electro-clinical diagnosis of CAE or JAE were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. The receiver operating characteristic (ROC) curve was used for the statistical analysis to predict a cutoff point for the age at onset of seizures between the syndromes.One hundred and ninety-six patients were studied. Generalized tonic-clonic seizure was reported by 134 patients (68.4%). The ROC curve of the age at seizure onset was an acceptable indicator to anticipate GTCS; the best cutoff point was at 9.65 years; 87 patients (44.4%) had CAE and 109 people (55.6%) had JAE. The odds ratio of the presence of GTCS in JAE compared with CAE was 3.6.Syndrome diagnosis of CAE vs. JAE has important practical implications. The age at onset of seizures serves as a reliable and meaningful variable to differentiate CAE from JAE.

The incidence of seizures may be as high as 11% in HIV-infected patients, with a long list of possible etiologies including acute symptomatic (provoked) causes, CNS opportunistic infections, malignancy, stroke, dementia, and immune reconstitution inflammatory syndrome, among others. The combination regimens of antiretroviral drugs used to treat HIV infection often include substrates, inducers, and inhibitors of several cytochrome P-450 isoenzymes, which are often also targeted by various antiseizure medications (ASMs). Complex interactions may occur when these ASMs are administered to patients receiving treatment for HIV infection.

Antiseizure medications (ASMs) may have adverse effects on the cardiovascular system. A number of serologic markers relevant to cardiovascular risk have been found to be affected by the CYP450-inducing ASMs. These include cholesterol and specific atherogenic lipid fractions, lipoprotein(a), C reactive protein, and homocysteine. These alterations suggest that enzyme-inducing ASMs might produce elevations in cardiovascular risk, a notion reinforced by the epidemiologic data. Therefore, monitoring vascular risk factors in patients receiving CYP450-inducing ASMs may be beneficial. In addition, patients with cardiovascular disorders are usually on antihypertensive, anticoagulant, or cardiac drugs, which may have significant interactions with ASMs.

The International League Against Epilepsy clinical definition of epilepsy allows a diagnosis of epilepsy after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Because for most forms of multiple sclerosis (MS) the risk is the same as for the general population, a single seizure may not require long-term antiseizure medication (ASM) treatment. Patients with MS who experience seizures that cannot be explained by any cause other than MS have focal epilepsy, and these patients often responded well to ASM monotherapy. The adverse-effect profile of ASMs and drug interactions with MS disease-modifying agents are significant determining factors in the selection of an appropriate ASM to treat seizure(s) in a patient with MS.

Although most people with epilepsy lead normal lives, neurobehavioral problems are found in a large proportion of patients with epilepsy than in the general population. Higher rates of psychopathology also are observed in people with epilepsy relative to the general population, to other neurological control groups, and to people with chronic non-neurological disorders. This largely reflects the effect of uncontrolled epilepsy and the underlying brain injury, which predispose patients to depression, anxiety, and other psychiatric symptoms. Some antiseizure medications (ASMs) are also psychotropic agents with either positive or negative effects. The psychotropic effects of ASMs in people with epilepsy are, however, variable and unpredictable.

Stroke and cerebrovascular lesions are the main cause of epilepsy in the elderly. Many similarities exist between cerebral ischemia and epilepsy regarding brain damage and autoprotective mechanisms that are activated following the injurious insult. Therefore, drugs that are effective in minimizing seizure-induced brain damage may also be useful in minimizing ischemic injury. On the other hand, some antiseizure medications (ASMs) may have detrimental effects in stroke patients, and there is evidence that recovery is worse in patients treated with particular ASMs after stroke. Thus, when selecting an ASM for a patient with stroke, one must consider its impact on comorbidity and comedications, its adverse effects, and its cost, among other factors.

Many antiseizure medications (ASMs) are associated with hematological toxicity. A wide spectrum of hematological abnormalities can be seen after prescribing an ASM, ranging from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, or even bone marrow failure. The magnitude of the problem is illustrated by the fact that at least one hematological abnormality was noted in 33% of patients taking valproate in one study. Fortunately, potentially fatal hematological disorders are rare; for example, aplastic anemia has an incidence of only a few cases per million per year. Nonetheless, knowledge of the hematological adverse effects of these drugs is crucial when selecting ASMs in patients with epilepsy.

Management of COVID-19 in people with epilepsy may be more complicated than that in other individuals. In general, it appears that people with COVID-19 are unlikely to develop seizures. However, patients critically ill with COVID-19 may develop seizures as a consequence of hypoxia, metabolic derangements, organ failure, or cerebral damage. Seizure in these critically ill patients must be recognized and stopped immediately. However, because these patients suffer from severe respiratory and/or cardiac problems, antiseizure medications (ASMs) with significant respiratory or cardiac adverse effects (e.g., phenytoin, phenobarbital) should be avoided. As well, the combination regimens used to treat COVID-19 often include substrates, inducers, and inhibitors of several cytochrome P-450 isoenzymes, and complex interactions may occur when some ASMs are administered to patients receiving treatment for coronavirus infection.

Several reports have already shown that chronic treatment with some antiseizure medications (ASMs) influences serum lipid profile, with high total cholesterol concentrations in patients receiving carbamazepine, phenytoin, phenobarbital, or primidone; high levels of HDL cholesterol in those receiving carbamazepine or phenytoin; high levels of LDL cholesterol in patients treated with carbamazepine and phenobarbital, and high triglyceride levels in patients receiving carbamazepine, phenobarbital, or phenytoin. The effects of ASMs on the serum levels of lipids and lipoproteins could be explained on the basis of different mechanisms. Patients receiving enzyme-inducing ASMs are significantly more likely to require multiple upward dose adjustments of their statin medication, so the clinician should assess the serum lipid profile in patients treated with enzyme-inducing ASMs.

Due to the potential for teratogenesis and other problems, the risks and benefits of antiseizure medication (ASM) therapy should be weighed carefully in pregnant women or in women of childbearing potential. Pregnancy should be planned in a patient receiving ASMs, so that appropriate measures can be taken in advance. It is essential to determine whether an ASM is still needed, which ASM is needed, if a change in ASM is beneficial, and what dose is required to control seizures. The most important consideration is balancing maternal seizure control against the risk to the developing fetus.

At the molecular level, the majority of antiseizure medications (ASMs) modulate excitatory and inhibitory neural transmission. ASMs probably exert their anticonvulsant effects at both the cell membrane and intracellularly. How the various drugs prevent or attenuate seizures is not fully understood, and the mechanisms described here only summarize some of their known potential effects on neurons and glia. Ideally, specific defect(s) that underlie epilepsy in individual patients would be identified and therapy targeted to correct the dysfunctional mechanism. In reality, such identification is rarely possible, and empiric therapy must be planned. The mechanisms described here will enhance fundamental understanding of the various agents. Knowledge of the pharmacokinetic properties of ASMs is crucial in selecting an appropriate agent in any particular clinical context.

Treating a patient with epilepsy involves more than just treating seizures. Many patients have associated learning and cognitive problems that can lead to significant difficulties at school or work, such as reductions in attention, IQ, language and perceptual skills, executive functions including problem-solving, verbal and visual memory, and motor speed. Children with epilepsy, even those with normal intelligence, often experience educational difficulties more often than unaffected children. These educational problems tend to persist into adulthood and are sometimes manifested as underemployment. The causes of cognitive impairment in patients with epilepsy include the effect of ongoing seizures, underlying structural brain lesions, and the adverse effects of antiseizure medications.

Drugs may sometimes aggravate seizures, defined as an increase in either the frequency or severity of existing seizures, the emergence of new types of seizures, or the occurrence of status epilepticus. Seizure aggravation can occur with virtually all antiseizure medications (ASMs). Pharmacodynamic aggravation of epilepsy usually translates into both increased seizure frequency and increased interictal electroencephalographic changes. A doubling or greater increase in seizure frequency may be considered as evidence for seizure aggravation. The underlying mechanisms for seizure aggravation with ASMs are not fully understood.

Drug interactions can occur whenever two or more drugs are administered simultaneously. Most clinically important antiseizure medication (ASM) interactions with other drugs result from induction or inhibition of drug-metabolizing hepatic enzymes or significant protein binding properties. Other mechanisms, such as pharmacodynamic interactions between drugs, also may plat a role. Because many ASMs are substrates, inducers, or inhibitors of hepatic enzymes and do exhibit significant protein binding, drug interactions are common in patients with epilepsy. Patients who have renal or hepatic disorders are especially vulnerable to drug interactions.

About 40% of patients with epilepsy will have “difficult-to-control” seizures. Focal epilepsies and symptomatic (structural-metabolic) generalized epilepsies are less likely to be controlled easily than the idiopathic (genetic) generalized epilepsies. Many physicians advocate combination therapy once two have failed in monotherapy, using a second drug that may have a different mechanism of action or a similar one. Little evidence shows that using two drugs with differing mechanisms of action (rational polytherapy) is superior to using two drugs with similar mechanisms of action. However, adverse effects may be worse when drugs with similar mechanisms of action are used, and use of differing drug types may offer benefit with regard to adverse effects.

Patients taking antiseizure medications (ASMs) have higher rates of osteopenia, osteoporosis, and bone fractures than the general population. The decrease in bone mineral density possibly attributed to ASM use leads to increased bone fragility and, hence, greater risk of fracture. When one considers that people with epilepsy have a greater propensity for falls as well, the reduction in bone density has even greater importance than usual for these patients. There are probably multiple causes of the increased rate of osteopenia and osteoporosis in epilepsy. Evidence suggests that ASMs may have negative effects on bone mineral density through a variety of mechanisms.

Idiosyncratic drug reactions are unexpected and unpredictable adverse reactions that are fundamentally different from the dose-related adverse effects of drugs. Drug-induced rashes are the most common type of idiosyncratic reaction caused by the use of antiseizure medications (ASMs). Most reactions are mildly to moderately uncomfortable rashes without systemic involvement, but occasionally the rash can be severe and present as erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis (Lyell syndrome). The ASM hypersensitivity syndrome (AHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is not common, but is important and potentially life-threatening. All cutaneous reactions to ASM administration must be evaluated promptly.

There is a correlation between the serum concentration of any antiseizure medication (ASM) and its therapeutic and toxic effects. Therapeutic drug monitoring seeks to optimize the desirable effects of ASMs while minimizing their undesirable properties. Because the therapeutic level varies between patients, the role of drug monitoring is somewhat controversial, with some clinicians holding the view that levels are irrelevant as long as seizures are controlled. However this requires hoping that a seizure does not occur while time passes, a situation that may be unacceptable to many patients. Therefore, it may be advantageous to obtain baseline serum levels to ensure that drug concentrations are within the range generally found in patients who either respond to medication or who take a dose known to be therapeutic.

In this chapter, the dosage forms, starting dose, titration schedule, maintenance dose, dose limits, and discontinuation schedule of various antiseizure medications (ASMs) are discussed. In addition, administration guidelines, contraindications, precautions, and information for patients are discussed briefly. A number of key points in the successful administration of ASMs are also discussed; among these, choosing the correct ASM for seizure type or syndrome; using the lowest possible dose to achieve seizure freedom; monitoring for adverse effects; weighing the relative risks and benefits of monotherapy versus polytherapy; and determining when surgical or non-medical therapies may be appropriate.

Two disorders are comorbid if they occur in the same person more frequently than by chance alone. Migraine and epilepsy appear to be comorbid. Migraine and epilepsy share several clinical features and may share some common pathophysiological mechanisms. Both are considered disorders of neuronal hyperexcitability, in that initial excessive neuronal activity in migraine leads to cortical spreading depression and aura, with the subsequent recruitment of the trigeminal nucleus leading to central sensitization and pain. In epilepsy, neuronal overactivity leads to the recruitment of larger populations of neurons firing in a rhythmic manner that constitutes an epileptic seizure. In addition, similar triggering factors have been identified for both migraine and epilepsy. Some antiseizure medications (ASMs) are effective in reducing migraine frequency.

Ophthalmologic problems in patients with epilepsy may be due to either the disease process or therapy with antiseizure medications (ASMs). Visual disturbances such as blurred vision, diplopia, and oscillopsia are generally benign, reversible, dose-dependent neurotoxic side effects of ASMs. Some ocular complaints may be related to the unique mechanistic properties of individual ASMs and can occur when they are administered at therapeutic levels. Vigabatrin and ezogabine have special retinal toxicity that has greatly limited their use. The clinician must vigilantly monitor patients for visual disturbances, often testing before any changes are noticed by the patient and immediately stopping the offending ASM when problems arise.

Variables that affect the suitability of a specific antiseizure medication (ASM) for patients with epilepsy include ASM-specific variables, patient-specific variables, and nation-specific variables. For many patients, several agents are good choices. However, for the generalized epilepsies, valproate may have the greatest efficacy, while in focal epilepsies many drugs are potentially good choices.

More than 30% of people with epilepsy have persistent seizures despite the use of appropriate therapies; these patients have drug-resistant epilepsy. Therefore, investigating and discovering new medications to treat epilepsy is of paramount significance. There are multiple dugs in the pipeline to treat epilepsy. This chapter briefly review some of these new antiseizure medications (ASMs), including fenfluramine, ganaxolone, anakinra, padsevonil, and everolimus.

Neuropathic pain is defined as pain caused by dysfunction or a primary lesion in the central or peripheral nervous system. Some antiseizure medications (ASMs) can suppress or attenuate pain in these conditions. It is assumed that both epilepsy and neuropathic pain share an underlying common pathophysiology, thus enabling some ASMs to be useful for several neuropathic pain conditions. Most ASMs reduce neuronal hyperexcitability by inhibiting ion channels, and they may act on different parts of the nociceptive pathway. Carbamazepine was approved for the treatment of trigeminal neuralgia years before it was approved to treat epilepsy. Carbamazepine, gabapentin, and pregabalin are currently the only three ASMs approved for the treatment of neuropathic pain syndromes.

Epilepsy is a common neurological problem in the elderly. Seizures in the elderly can be caused by strokes, brain tumors, trauma, infectious causes, toxic and metabolic causes, and degenerative diseases. While similar principles of drug selection apply to elderly individuals and to younger patients, certain factors carry greater weight in the elderly. Selection of the appropriate therapy should be guided by the recognition that older patients often have comorbidity and receive multiple medications. Decreased efficiency of renal and hepatic clearance and altered metabolism must all be considered when choosing a safe and effective antiseizure medication for an elderly patient.

The prevalence of epilepsy ranges between 0.6% and 1%, and perhaps 70 million worldwide suffer from this condition. The mainstay of treatment is drug therapy. In the past decade, many new antiseizure medications (ASMs) have been introduced, so that there are now approximately 30 medications available to treat epilepsy. The healthcare provider therefore has many choices. However, having many alternatives also allows for the possibility of choosing an inappropriate or a suboptimal agent. For most seizures, there is little difference in efficacy between the different agents, and other factors chiefly influence drug selection. These include the potential adverse effects, comorbid conditions, concomitant medications, age, and gender, among others. The choice of medication should be guided by knowledge and familiarity with the ASMs. This book is designed as a practical tool for physicians and other healthcare providers. While the authors include a brief formal discussion of the basic pharmacology of each ASM, this text emphasizes how to select and use ASMs in a variety of clinical contexts. The authors discuss choosing drugs when faced with various medical comorbidities; how to correctly prescribe, titrate, and taper drugs; how to monitor drug efficacy and side effects; how to diagnose and manage toxicity; interactions with other drugs; and other relevant issues. The text is designed to fill an unmet need and should lead to improved patient care.

The use of antiseizure medications (ASMs) in the presence of renal insufficiency is associated with an increased risk of adverse effects. Renal failure is often accompanied by other medical problems that can influence drug levels. These include gastroparesis, which slows absorption, and bowel edema, which may reduce absorption. There is often a decrease in gut cytochrome P-450 metabolism and P-glycoprotein active transport as well, which can affect how much of the drug enters portal circulation. Renal failure is also associated with hypoalbuminemia, which may influence free plasma concentrations of ASMs that are highly protein bound. Knowledge of the mechanisms of elimination of these drugs is crucial when selecting an ASM in patients with renal impairment.

Many patients with epilepsy experience weight change after starting an antiseizure medication (ASM). Some ASMs are associated with weight loss, some with weight gain, and others have no effect on weight. Weight gain is associated with an increased risk of comorbidities (e.g., type 2 diabetes mellitus and heart diseases) and impairs quality of life and self-esteem; weight loss can also have adverse effects on a patient’s health and self-esteem. Taking these issues into consideration, the clinician should carefully weigh the possible weight-influencing side effects of particular ASMs and tailor their use to the patient’s needs.