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Epidemiological and medical aspects of epilepsy in the elderly
Abstract
Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.
... Ein Grund hierfür ist die Semiologie, die sich von jüngeren Erwachsenen unterscheidet. Im Alter treten Anfälle oft in Form fokal nicht bewusst erlebter Anfälle mit Arrest, ohne klassische Symptome wie Automatismen oder psychische Phänomene, auf [26,27,28], und bilateral tonisch klonische Anfälle sind im Vergleich zu jungen Erwachsenen (65 %) seltener (26 %) [27]. Auren werden seltener berichtet und manifestieren sich oft unspezifisch in Form von Schwindel [27]. ...
... Ein Grund hierfür ist die Semiologie, die sich von jüngeren Erwachsenen unterscheidet. Im Alter treten Anfälle oft in Form fokal nicht bewusst erlebter Anfälle mit Arrest, ohne klassische Symptome wie Automatismen oder psychische Phänomene, auf [26,27,28], und bilateral tonisch klonische Anfälle sind im Vergleich zu jungen Erwachsenen (65 %) seltener (26 %) [27]. Auren werden seltener berichtet und manifestieren sich oft unspezifisch in Form von Schwindel [27]. ...
... Im Alter treten Anfälle oft in Form fokal nicht bewusst erlebter Anfälle mit Arrest, ohne klassische Symptome wie Automatismen oder psychische Phänomene, auf [26,27,28], und bilateral tonisch klonische Anfälle sind im Vergleich zu jungen Erwachsenen (65 %) seltener (26 %) [27]. Auren werden seltener berichtet und manifestieren sich oft unspezifisch in Form von Schwindel [27]. Symptome wie Innehalten oder eine häufig prolongiert bestehende postiktale Desorientiertheit [28] können z. ...
Zusammenfassung
Epilepsien stellen nach Demenzen und Schlaganfall die dritthäufigste neurologische Krankheitsgruppe bei älteren Menschen dar. Die Inzidenz der Epilepsien steigt im Alter, sodass aufgrund demografischer Entwicklungen in den kommenden Jahren mit einer weiteren Zunahme älterer Patienten mit Epilepsie zu rechnen ist. Die häufigsten Ursachen der Altersepilepsie stellen zerebrovaskuläre Erkrankungen und Demenzen dar. Anfälle bei älteren Menschen werden oft spät erkannt. Das Auftreten eines Status epilepticus ist bei älteren Patienten häufiger und mit erhöhter Morbidität und Letalität vergesellschaftet. Die medikamentöse Behandlung älterer Patienten wird durch Komorbiditäten und Polypharmazie erschwert, wobei Antiepileptika mit geringem Interaktionsprofil und guter Verträglichkeit zur Behandlung der Altersepilepsie gewählt werden sollten. Levetiracetam und Lamotrigin sind aufgrund geringer Interaktionen und guter Verträglichkeit Antiepileptika erster Wahl beim älteren Patienten.
... The advent of EEG by Hans Berger in 1929 began when he recorded cortical oscillatory activity from the surface of the skull in humans. 2 Scalp electrodes record the electrical brain activity which reflects the summation of excitatory and inhibitory postsynaptic potentials in apical dendrites of pyramidal neurons in the more superficial layers of the cortex. 3 The association between cortical frequency bands of delta (1)(2)(3)(4), theta (4-7 Hz), alpha (8)(9)(10)(11)(12), beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) and gamma (>30 Hz) oscillations with different behavioural and disease states have been explored. ...
... 24 The study's findings concurred with previous epidemiological studies that showed that elderly population has a high incidence and prevalence of epilepsy. 25 The elderly population are prone to seizures due to the various comorbidity that includes stroke, brain tumours, infections, head trauma, dementia and metabolic-toxic syndromes. The utilisation of EEG to determine changes in the neuropsychological aspects has improved the understanding of diseases in the elderly. ...
Introduction:
Electroencephalogram (EEG) is an important investigational tool that is widely used in the hospital settings for numerous indications. The aim was to determine factors associated with abnormal EEG and its clinical correlations in hospitalised patients.
Materials and methods:
Patients with at least one EEG recording were recruited. The EEG and clinical data were collated.
Results:
Two hundred and fifty patients underwent EEG and 154 (61.6%) were found to have abnormal EEG. The abnormal changes consist of theta activity (79,31.6%), delta activity (20, 8%), focal discharges (41,16.4%) and generalised discharges (14, 5.6%). Older patients had 3.481 higher risk for EEG abnormalities, p=0.001. Patients who had focal seizures had 2.240 higher risk of having EEG abnormalities, p<0.001. Low protein level was a risk for EEG abnormalities, p=0.003.
Conclusion:
This study emphasised that an abnormal EEG remains a useful tool in determining the likelihood for seizures in a hospital setting. The risk factors for EEG abnormality in hospitalised patients were age, focal seizures and low protein level. The EEG may have an important role as part of the workup in hospitalised patients to aid the clinician to tailor their management in a holistic manner.
... Epilepsy presents somewhat differently in this age group relative to younger patients, with older patients having longer periods of post-ictal confusion and experiencing status epilepticus more frequently. 22 Further, the treatment of epilepsy in this population can be challenging due to potential medication interactions, a high frequency of adverse events at lower doses and serum concentrations than in younger patients, and the high risk of osteoporosis in older women. 22 Given the challenges of medically treating epilepsy in older adults, surgical remediation offers an opportunity to reduce epilepsy-related morbidity and mortality in this age group. ...
... 22 Further, the treatment of epilepsy in this population can be challenging due to potential medication interactions, a high frequency of adverse events at lower doses and serum concentrations than in younger patients, and the high risk of osteoporosis in older women. 22 Given the challenges of medically treating epilepsy in older adults, surgical remediation offers an opportunity to reduce epilepsy-related morbidity and mortality in this age group. ...
Background:
Despite its effectiveness, surgery for drug-resistant epilepsy is underutilized. However, whether epilepsy surgery is also underutilized among patients with stroke-related drug-resistant epilepsy is unclear. Therefore, our objectives were to estimate the rates of epilepsy surgery assessment and receipt among patients with stroke-related drug-resistant epilepsy and to identify factors associated with these outcomes.
Methods:
We used linked health administrative databases to conduct a population-based retrospective cohort study of adult Ontario, Canada residents discharged from an Ontario acute care institution following the treatment of a stroke between January 1, 1997, and December 31, 2020, without prior evidence of seizures. We excluded patients who did not subsequently develop drug-resistant epilepsy and those with other epilepsy risk factors. We estimated the rates of epilepsy surgery assessment and receipt by March 31, 2021. We planned to use Fine-Gray subdistribution hazard models to identify covariates independently associated with our outcomes, controlling for the competing risk of death.
Results:
We identified 265,081 patients who survived until discharge following inpatient stroke treatment, 1,902 (0.7%) of whom subsequently developed drug-resistant epilepsy (805 women; mean age: 67.0 ± 13.1 years). Fewer than six (≤0.3%) of these patients were assessed for or received epilepsy surgery before the end of follow-up (≤55.5 per 100,000 person-years). Given that few outcomes were identified, we could not proceed with the multivariable analyses.
Conclusions:
Patients with stroke-related drug-resistant epilepsy are infrequently considered for epilepsy surgery that could reduce morbidity and mortality.
... The incidence of epilepsy demonstrates a bimodal distribution with case numbers being highest in those under 5 years of age and in later life. 3,4 Data also suggest that the incidence of adult-onset epilepsy may be increasing in later life across both sexes. 5 The exact age at which a person may be defined as having "late-onset epilepsy" (LOE) remains poorly specified, although there is a likely inflection point at around the age of 50 years with a progressive increase in incidence thereafter. ...
... 5 The exact age at which a person may be defined as having "late-onset epilepsy" (LOE) remains poorly specified, although there is a likely inflection point at around the age of 50 years with a progressive increase in incidence thereafter. 3,6 The Cardiovascular Health Study estimated an incidence rate of around 2.5 cases per 1000 person years in older adults. 7 Similarly, once standardized for age, the prevalence of "idiopathic epilepsy" as captured by the Global Burden of Disease report shows a bimodal pattern across high and lowincome countries with an overall prevalence of epilepsy of 5.4 per 100 older people. ...
Epilepsy is most common in older people and yet optimizing the management of seizures in this demographic has often been somewhat overlooked. With populations aging across the world and those with complex early-onset epilepsies thankfully living into later life, the prevalence of epilepsy in older people is escalating rapidly. Assessment and management in this age group can be challenging. Seizures may present in unusual ways and the complex comorbidities and polypharmacy that often characterize older age, might make establishing a diagnosis of epilepsy in older persons difficult. Drug choices and treatment options are often more limited and need to be specifically tailored to the older individual with careful consideration of relevant comorbidities. The complex inter-relationship between epilepsy, dementia, and vascular disease in older people would seem a research priority, as there might be interventions to help reduce adverse outcomes in a growing and potentially vulnerable group.
... Las crisis epilépticas tónicoclónicas generalizadas se observaron en el 27% de los pacientes evaluados, y el 13% de los pacientes presentaron crisis epilépticas tónico-clónicas focales y secundariamente generalizadas. En otro estudio, se encontró que las crisis epilépticas tónico-clónicas generalizadas secundarias ocurrían en solo el 26% de los pacientes AM, en comparación con el 65% de los adultos más jóvenes (27). ...
... Cuando el médico opta por los FAE para los AM, es importante considerar la posibilidad de interacciones farmacológicas, ya que muchos de estos pacientes toman otros fármacos para enfermedades comórbidas. En este sentido, cuanto menor sea la unión a proteínas y menor sea el metabolismo hepático de los FAE, más fácil será su uso y menor será el riesgo de interacción con otros posibles fármacos concomitantes (27,32). ...
Elderly people are at a higher risk of developing epilepsy. With a progressive increase in life expectancy, this is the fastest growing group of epilepsy patients. Their treatment is complicated by the presence of physiological changes related to aging, comorbidities, concomitant cognitive problems, complex drug interactions, and difficulties in the adherence to medication regimes. Seizures can be controlled in elderly people patients with low doses of a single epileptic seizure drug. Tolerability is an important factor in drug selection, as elderly people patients tend to be very sensitive to side effects. Enzyme-inducing anti-seizure drugs should gradually be left out of the therapeutic arsenal in favor of new anti-seizure drugs that have shown similar efficacy and better tolerability. Levetiracetam and lamotrigine are the most recommended anti-seizure drugs for older adults with epilepsy nowadays. Although it could be easily controlled, it is recommended that older adults continue their treatment indefinitely, due to the recurrent seizures’ proclivity. More studies are needed to address the pathophysiological mechanisms of epilepsy in this age group, and greater inclusion of elderly people in clinical trials is needed, as is the development of comprehensive care models to provide optimal patient care.
... Convulsive seizures are not frequent in late-onset epilepsy and should be distinguished from tonic-clonic syncope [90]. Old people mostly suffer of focal impaired-awareness seizures [91,92] and can develop prolonged behavioral arrest with postictal confusion lasting for hours and sometimes days; auras and automatisms are both uncommon and often nonspecific [91,92]. The differential diagnosis includes subtle clinical phenomena typical of the elderly such as fluctuating cognitive impairment and delirium. ...
... Convulsive seizures are not frequent in late-onset epilepsy and should be distinguished from tonic-clonic syncope [90]. Old people mostly suffer of focal impaired-awareness seizures [91,92] and can develop prolonged behavioral arrest with postictal confusion lasting for hours and sometimes days; auras and automatisms are both uncommon and often nonspecific [91,92]. The differential diagnosis includes subtle clinical phenomena typical of the elderly such as fluctuating cognitive impairment and delirium. ...
The incidence of epilepsy is highest at the extreme age ranges: childhood and elderly age. The most common syndromes in these demographics – self-limited epilepsies of childhood and idiopathic generalized epilepsies in pediatric age, focal epilepsy with structural etiology in older people – are expected to be drug responsive.
In this work, we focus on such epilepsy types, overviewing the complex clinical background of unexpected drug-resistance. For self-limited epilepsies of childhood and idiopathic generalized epilepsies, we illustrate drug-resistance resulting from syndrome misinterpretation, reason on possible unexpected courses of epilepsy, and explicate the influence of inappropriate treatments. For elderly-onset epilepsy, we show the challenges in differential diagnosis possibly leading to pseudoresistance and analyze how drug-resistant epilepsy can arise in stroke, neurocognitive disorders, brain tumors, and autoimmune encephalitis.
In children and senior people, drug-resistance can be regarded as a hint to review the diagnosis or explore alternative therapeutic strategies. Refractory seizures are not only a therapeutic challenge, but also a cardinal sign not to be overlooked in syndromes commonly deemed to be drug-responsive.
... Numerous studies showed that, since the adulthood, there is a progressive and constant increase in both the incidence and prevalence of epileptic seizures and epilepsy in the general population (2). This is independent of the socio-cultural and economic context examined, affecting both developed and low-income countries (3). In particular, in the richer communities (i.e., Europe and USA), where the majority of the population consists of old people, epilepsy with onset in the elderly has significant economic and social repercussions (4). ...
... In most cases, LOE is characterized by focal seizures, secondary to brain damage, particularly cerebrovascular and infectious diseases, brain tumors, metabolic, and toxic conditions (3). More recent evidence reports that LOE can also be associated with neurodegenerative conditions, particularly Alzheimer's disease (AD). ...
Epilepsy is classically considered a childhood disease. However, it represents the third most frequent neurological condition in the elderly, following stroke, and dementia. With the progressive aging of the general population, the number of patients with Late-Onset Epilepsy (LOE) is constantly growing, with important economic and social consequences, in particular for the more developed countries where the percentage of elderly people is higher. The most common causes of LOE are structural, mainly secondary to cerebrovascular or infectious diseases, brain tumors, trauma, and metabolic or toxic conditions. Moreover, there is a growing body of evidence linking LOE with neurodegenerative diseases, particularly Alzheimer's disease (AD). However, despite a thorough characterization, the causes of LOE remain unknown in a considerable portion of patients, thus termed as Late-Onset Epilepsy of Unknown origin (LOEU). In order to identify the possible causes of the disease, with an important impact in terms of treatment and prognosis, LOE patients should always undergo an exhaustive phenotypic characterization. In this work, we provide a detailed review of the main clinical and instrumental techniques for the adequate characterization of LOE patients in the clinical practice. This work aims to provide an easy and effective tool that supports routine activity of the clinicians facing LOE.
... It has long been known that AD patients are at increased risk of developing seizures and epilepsy (Friedman et al., 2012;Vossel et al., 2013Vossel et al., , 2017. Earlyonset familial AD (EOFAD), caused by genetic mutations in APP, presenilin 1 (PSEN1), and presenilin 2 (PSEN2), is associated with a remarkable 87-fold higher seizure incidence compared with the general population (Amatniek et al., 2006;Cloyd et al., 2006). In contrast, the late-onset sporadic AD is associated with a 3-fold rise in seizure incidence (Amatniek et al., 2006;Cloyd et al., 2006). ...
... Earlyonset familial AD (EOFAD), caused by genetic mutations in APP, presenilin 1 (PSEN1), and presenilin 2 (PSEN2), is associated with a remarkable 87-fold higher seizure incidence compared with the general population (Amatniek et al., 2006;Cloyd et al., 2006). In contrast, the late-onset sporadic AD is associated with a 3-fold rise in seizure incidence (Amatniek et al., 2006;Cloyd et al., 2006). Also, AD severity was reported to correlate with seizure occurrence. ...
Alzheimer's disease (AD) is the most frequent neurodegenerative disorder that commonly causes dementia in the elderly. Recent evidence indicate that network abnormalities, including hypersynchrony, altered oscillatory rhythmic activity, interneuron dysfunction, and synaptic depression may be key mediators of cognitive decline in AD. In this review, we discuss characteristics of neuronal network excitability in AD, and the role of Aβ and Tau in the induction of network hyperexcitability. Many patients harboring genetic mutations that lead to increased Aβ production suffer from seizures and epilepsy prior to the development of plaques. Similarly, pathological accumulation of hyperphosphorylated tau has been associated with hyperexcitability in the hippocampus. We present common and divergent roles of tau and Aβ on neuronal hyperexcitability in AD, and hypotheses that could serve as a template for future experiments.Significance statementAbnormal neuronal network excitability may lead to hypersynchrony, aberrant oscillatory rhythmic activity and interneuron dysfunction, which may contribute to cognitive decline in Alzheimer's disease. The main goals of this review are: (1) to provide an overview of the current knowledge on the association between abnormal network dysfunction and Alzheimer's disease; (2) discuss the role of pathological Aβ and tau on neuronal hyperexcitability; and (3) present potential hypotheses that can be tested for future studies, which could lead to more effective strategies to prevent, diagnose and manage AD and related disorders.
... Moreover, the duration of postictal confusion is longer in elderly patients than in other adult patients, sometimes lasting for days or even weeks. 10 Elderly patients are more susceptible to injuries caused by seizures, and falls may also result in head injury or bone fracture. 10 In addition to the previously mentioned clinical characteristics, the incidence of status epilepticus (SE) is higher among elderly patients than in other age groups. ...
... 10 Elderly patients are more susceptible to injuries caused by seizures, and falls may also result in head injury or bone fracture. 10 In addition to the previously mentioned clinical characteristics, the incidence of status epilepticus (SE) is higher among elderly patients than in other age groups. 24 The mortality rate associated with SE varies with age, and is approximately 50% among individuals aged >80 years. ...
The incidence and prevalence of epilepsy are highest in elderly people, and the etiologies of epilepsy in the elderly differ from those in other age groups. Moreover, diagnosing and treating epilepsy in elderly people may be challenging due to differences in clinical characteristics and physiological changes associated with aging. This review focuses on the pharmacological treatment of epilepsy in elderly patients.
... [91]. Moreover, the highest incidence of epilepsy was observed among the elderly [92]. Notably, status epilepticus, a state of prolonged seizure activity, is most frequently reported in infants and the elderly [93]. ...
Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.
... The lack of anti-seizure drugs is another factor contributing to the prevalence of epilepsy in a number of countries (30). Epilepsy has different effects at different ages, although it is most prevalent in two age groups: 5 to 9 years old and about 80 years old (31,32). ...
Introduction. Epilepsy is one of the most common neurological diseases. It is an uncontrollable neuronal activity of different parts of the brain leading to convulsion and/or fainting. Although epileptic seizure control and therapeutics have significant advances, 20-30% of individuals still have uncontrolled seizures. Patients under the medication's control are not free from the drug's side effects and complications. Epileptic patients experience many different challenges. Transcranial direct current stimulation (tDCS) is a safe and non-invasive brain stimulation method applied in drug-resistant seizures and epilepsies. It transmits positive/negative electrical current toward deep brain parts, modulating their electrical activity. Methods. This is a review article. All relevant articles which were accessible were reviewed. The effectiveness of tDCS in preventing epilepsy in patients undergoing seizures was reviewed in this article. Conclusion. According to the studies, this method can probably be an auxiliary method in preventing and treating seizures. As epileptic seizures were induced and confirmed in some studies after the application of tDCS, the method should be cautiously applied.
... The prevalence of epilepsy, a chronic neurodegenerative disease, ranges from 0.5% to 2% worldwide (1). In a study by Zack and Kobau, (2), they reported that the prevalence of epilepsy rose by 24% between 2010 and 2015 in the USA. ...
... 19,20) Older patients with epilepsy are usually on multiple medications due to their comorbidities, 21) and adverse effects are more likely to occur as a result of decreased metabolism and excretion capacity. 22) Consequently, for these patients, new ASMs are often selected 23) because of their few drug interactions 10) and high tolerability. 11) Conversely, in terms of drug economics, new ASMs tend to be more expensive than conventional ASMs, which may prevent their use in treatment. ...
Patients in Japan often have difficulty in screening and selecting chronic-care and rehabilitation hospitals for transfer because of the high cost and unavailability of new antiseizure medications, such as perampanel and lacosamide. To investigate whether the requirement for perampanel and lacosamide interfered with patients’ hospital transfer by comparing the number of days required for hospital transfer. Data were obtained from patients 1) who were diagnosed with intracerebral hemorrhage or cerebral infarction, 2) who were treated with antiseizure medications for epilepsy, and 3) who were transferred to another hospital. The main outcome measures were the length of hospital stay and days from the last seizure to hospital transfer.Ninety-four eligible patients were divided into those treated with perampanel or lacosamide (n = 18) and those treated with other agents (n = 76). The mean length of hospital stay and days from the last seizure to hospital transfer were 52.9 and 45.4 d in the perampanel and lacosamide group, and 32.7 and 28.6 d in the other medication group (p < 0.001). The mean antiseizure medication costs and total drug costs were U.S. $4.88 and $6.85 in the perampanel/lacosamide group and U.S. $1.94 and $4.41 in the other medication group (p < 0.001, p = 0.007), respectively. Considering antiseizure medication availability and cost in the transfer destination hospital is important when choosing medications for patients requiring hospital transfer from an acute-care hospital.
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... Ginger has been shown to have extraordinary effects on epilepsy patients who suffer from recurring seizures. When compared to younger individuals, epilepsy in the elderly has fewer pre-symptoms and a longer duration of postictal disorientation [70][71][72]. This effect could be linked to the substantial changes in brain anatomy that occur as a result of ventricular expansion speeding up as people get older [73]. ...
Ginger (Zingiber officinale), a Zingiberacae family member, is a popular spice all around the world. This perennial creeping plant has long leaves, vivid green flowers, and a strong tuberous rhizome. Throughout history, several cultures and civilizations have recognized the potential of ginger in the treatment and prevention of disease. Various research with ginger and its extract support the potential effect in a variety of applications. Ginger has been used medicinally for over 2000 years and is regarded as one of the most versatile medicinal herbs, with a wide range of biological properties. Since ancient times, ginger has been used to cure a variety of conditions including heart problems, menstrual disorders, food poisoning, osteoarthritis, epilepsy, nausea, inflammation, cough and cold, motion sickness, menstrual cramps, cancer, and many others. Apart from that, it has antibacterial and antioxidant properties. The presence of gingerol and paradol, as well as shogaols and other chemicals, is responsible for ginger’s medicinal properties. The medical benefits of ginger and current knowledge provide a solid platform for future research into how it can protect humans from a number of diseases.
... Cerebrovascular disease is the most common etiology in the elderly, and seizure etiology is unknown for almost half of all elderly patients [3]. Although 70 % of elderly patients obtain seizure-freedom with anti-seizure medications (ASMs), patients over 60 are at a higher risk of status epilepticus and are less tolerant of ASMs than younger patients [3][4][5][6]. ...
Objective
The object of this case series is to report the effectiveness and complication rates of presurgical evaluation and surgical treatment among elderly epilepsy patients in our clinic.
Methods
We reviewed patients charts from 2016 to 2020 and identified patients over the age of 55 years of age who underwent intracranial EEG, resection, and device placement. We compared the complications and post-intervention outcomes of 14 different patients.
Results
The mean age of patients was 63.6 ± 4.13 years, and 6 (42.9 %) patients were female. 8 (57.1 %) patients underwent intracranial evaluation; 6 patients underwent SEEG, and 2 patients underwent SDE placement. 5/11 (45 %) patients reached seizure freedom with at least one year follow-up.
Discussion
Intracranial evaluation could play an important role in the success of surgical intervention in the elderly epilepsy population. Prospective, multicenter studies are needed to determine the ideal candidate for a safe and effective intracranial evaluation and resection.
... Our study groups were roughly comparable with regard to the seizure type, although FAS was more common in AE (14/21 vs. 6/25) and FTBTCS appeared slightly more frequent in LOEUO (15/25 vs. 8/21). These findings are in line with previous articles, reporting generalized tonic-clonic seizures in 30-47% of cases of epilepsy in the elderly (6)(7)(8)20), although proper comparisons are difficult due to differences in the study populations. In our LOEUO cohort, 5/25 patients reported FTBTCS as the only seizure type (mainly occurring at night), which was never the case among the subjects with AE (p = 0.053). ...
Introduction
Late-onset epilepsy (LOE) has recently become a topic of intense research. Besides stroke, tumors, and dementia, autoimmune encephalitis (AE) has emerged as another possible cause of recurrent seizures in the elderly, and may account for a proportion of cases of LOE of unknown origin (LOEUO). This 24-h ambulatory electroencephalography (AEEG)-based study compared patients with LOEUO and AE to identify features suggestive of immune-mediated seizures in the elderly.
Materials and methods
We retrospectively reviewed 232 AEEG examinations performed in patients over 55 years with ≥6-month follow-up, and selected 21 subjects with AE and 25 subjects with LOEUO. Clinical charts and AEEG recordings were carefully analyzed.
Results
Twenty-five patients with LOEUO (12 women, mean age at onset 67.9 years) and 21 AE subjects (8 women, mean age at onset 65.7 years) were enrolled. High-frequency seizures were reported in 20/21 AE and 7/25 LOEUO cases (p < 0.00001). Focal aware seizures were more common in AE (14/21 vs. 6/25, p = 0.00058), whereas “isolated” focal-to-bilateral tonic-clonic seizures occurred in 5/25 patients with LOEUO only (p = 0.053). AE subjects reported ictal autonomic manifestations more frequently (p = 0.0033). Three-hundred-seventy and 24 seizures were recorded in 13/21 patients with AE and 3/25 patients with LOEUO, respectively (p = 0.0006). Interictal epileptiform discharges were observed in 70% of both groups, but their sleep activation was more common in AE (p = 0.06).
Conclusion
Our study shows that high-frequency focal seizures with autonomic manifestations should raise the suspicion of AE in the elderly with new-onset seizures. It also highlights the relevant contribution of AEEG, which might reduce the diagnostic delay and provide useful clues to recognize AE.
... Эпидемиология. Эпилепсия у пожилых встречается чаще, чем в среднем возрасте [194]. По нашим данным, наибольшая распространённость заболевания у взрослых была отмечена на 2-3-м десятилетиях жизни, составив 5,4 на 1000 населения, в среднем возрасте этот показатель был несколько ниже -3,3-3,5, а у лиц старше 70 лет вновь отмечен его рост -до 4,2 на 1000 населения в популяции лиц преклонного возраста (Московская область) [40]. ...
The monograph presents methods for diagnosing and treating epilepsy in adults. Every effort has been made by the authors and the publisher to ensure the accuracy of the indications, adverse reactions, and recommended doses of medications given in this book. However, this information is subject to change. The information contained in the book is intended for physicians. Carefully read the manufacturer's instructions for use of medicinal products. For neurologists, doctors of other specialties and medical students.
... Neuronal hyperactivity is also associated with a number of maladaptive changes in human subjects as well as rodents, including cognitive decline (Reagh et al. 2018), enhanced seizure susceptibility (Cloyd et al. 2006;Stover et al. 2017), and the accumulation of tau but not beta-amyloid (Huijbers et al. 2019). Moreover, reducing neuronal hyperactivity in humans and rodents is sufficient to reduce cognitive deficits (Bakker et al. 2012;Hunsberger et al. 2015b;Koh et al. 2010;Sanchez et al. 2012), suggesting not only an association but a causative relationship between hyperactivity and cognitive decline. ...
The greatest risk factor for development of the deadly neurodegenerative disorder known as Alzheimer’s disease (AD) is advancing age. Currently unknown is what mediates the impact of advanced age on development of AD. Also unknown is what impact activity alterations in the entorhinal cortex (EC) has on the spread of AD pathology such as pathological tau through the brain as AD progresses. This review focuses on evidence in the literature that describes how one potential age-related change, that of glutamate-mediated increases in neuronal activity, may ultimately increase the risk of developing AD and promote the spread of tau pathology in AD-affected brains from the EC to later regions such as the hippocampus and prefrontal cortex. A better understanding of these detrimental alterations may allow for earlier detection of AD, offering a better prognosis for affected individuals.
... Epilepsy and new onset seizures in elderly patients are an important health issue of the aging population (1,2). Epileptic seizures are a core symptom of autoimmune encephalitis (AE) (3,4), and autoimmune epilepsy has been reported to account for up to 20% of epilepsy of unknown etiology (5). ...
Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).
Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the University of Greifswald, Germany. A total of 225 patients aged ≥50 years with epileptic seizures were enrolled and underwent an MRI/CT scan, profiling of neural antibodies (AB) in serum and cerebrospinal fluid (CSF), and neuropsychological testing. On the basis of their work-up, patients were categorized into the following three cohorts: definite, suspected, or no AE. Patients with definite and suspected AE were subsequently treated with immunosuppressive therapy (IT) and/or anti-seizure drug (ASD) therapy and were followed up (FU) regarding clinical and seizure outcome.
Results: Of the 225 patients, 17 (8%) fulfilled the criteria for definite or suspected AE according to their AB profile and MRI results. Compared with patients with no evidence of AE, those with AE were younger (p = 0.028), had mesial temporal neuropsychological deficits (p = 0.001), frequently had an active or known malignancy (p = 0.006) and/or a pleocytosis (p = 0.0002), and/or had oligoclonal bands in CSF (p = 0.001). All patients with follow-up became seizure-free with at least one ASD. The Modified Rankin scale (mRS) at hospital admission was low for patients with AE (71% with mRS ≤2) and further decreased to 60% with mRS ≤2 at last FU.
Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. AB testing in CSF and sera, cerebral MRI, CSF analysis, and neuropsychological testing for mesial temporal deficits should be part of the diagnostic protocol for AE following late-onset seizures.
... In this study, history of status epilepticus was significantly associated with poor outcome of epilepsy. This was also reported in many studies [11,19,26]. Between 10 and 30% of people who have status epilepticus die within 30 days [27]. ...
Background
Elderly people with epilepsy are large, but neglected group. Data on the predictive factors for recurrent seizures in the elderly population are inconclusive or are not known for the majority of patients. This is especially true for the Egyptian population as no specific study was concluded to address this issue before.
Objectives
The aim of this study was to detect the predictive factors of epilepsy outcome in a sample of Egyptian aged population.
Materials and methods
A total of 100 patients aged 50 years or older with epilepsy diagnosed according to International League Against Epilepsy (ILAE) latest definition were included in the study and followed up for 6 months as regards seizure control. All participants were prospectively evaluated for epidemiological, clinical, radiological, electrodiagnostic, and laboratory data.
Results
The outcome was statistically significant affected in relation to absence of medical comorbidities ( P = 0.037), seizure etiology ( P = 0.007), history of status epilepticus ( P < 0.001), MRI brain findings ( P = 0.005), EEG changes ( P < 0.001), Ca ( P = 0.01), and Mg level ( P = 0.046).
Conclusion
We conclude that aged Egyptian epileptic population with no medical comorbidities, normal MRI brain, or normal EEG can be predicted to have good outcome of their epilepsy while patients with post stroke epilepsy, abnormal MRI brain, and abnormal EEG, with low serum Ca or Mg level can be predicted to have poor outcome.
... They relate to a worse neurological outcome and higher mortality in the short term [2][3][4][5][6]. Long-term consequences are, amongst others, loss of independence, impaired self-confidence, and a higher risk of fractures after falling [7][8][9]. Prevention of seizures would therefore be worthwhile. In animal studies, several antiepileptic drugs have shown antiepi-This is an Open Access article licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense), ...
Objective:
The frequency of seizures after stroke is high, with a severe impact on the quality of life. However, little is known about their prevention. Therefore, we investigated whether early administration of diazepam prevents the development of seizures in acute stroke patients.
Methods:
We performed a substudy of the EGASIS trial, a multicenter double-blind, randomized trial in which acute stroke patients were treated with diazepam or placebo for 3 days. Follow-up was after 2 weeks and 3 months. The occurrence of seizures was registered prospectively as one of the prespecified secondary outcomes.
Results:
784 EGASIS patients were eligible for this substudy (389 treated with diazepam [49.6%] and 395 treated with placebo [50.4%]). Seizures were reported in 19 patients (2.4% of the total patient group). Seizures occurred less frequently in patients treated with diazepam (1.5 vs. 3.3% in the placebo group); however, this difference was only statistically significant in patients with a cortical anterior circulation infarction (0.9% in the diazepam group vs. 4.6% in the placebo group, incidence rate ratio 0.20, 95% CI: 0.05-0.78, p = 0.02, NNT = 27).
Conclusion:
We found that a 3-day treatment with diazepam after acute cortical anterior circulation stroke prevents the occurrence of seizures in the first 3 months following stroke.
... 1,2 It is also estimated that epilepsy affects 1% of patients aged over 65 and that the majority of these cases (20-40%) are secondary to cerebrovascular disease. 3,4 The risk factors for developing seizures have been identified as cerebral haemorrhage,cortical location of lesion and the severity of stroke, for example those involving multiple lobes. 5,6,7 The incidence of seizures has a bimodal distribution with a peak two weeks post-stroke and a second peak 6-12 months post-stroke. ...
... GTC seizures are major convulsive episodes and are always associated with a loss of consciousness 15 . ...
Importance
Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes.
Objective
To investigate associations of PTE with dementia risk.
Design, Setting, and Participants
The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years. Data were analyzed between March 14, 2023, and January 2, 2024. The study took place in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC study participants initially enrolled, 2061 were ineligible and 1173 were excluded for missing data, resulting in 12 558 included participants.
Exposures
Head injury was defined by self-report and International Classification of Diseases ( ICD ) diagnostic codes. Seizure/epilepsy was defined using ICD codes. PTE was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after head injury. Head injury, seizure/epilepsy, and PTE were analyzed as time-varying exposures.
Main Outcomes and Measures
Dementia was defined using cognitive assessments, informant interviews, and ICD and death certificate codes. Adjusted Cox and Fine and Gray proportional hazards models were used to estimate dementia risk.
Results
Participants had a mean (SD) age of 54.3 (5.8) years at baseline, 57.7% were female, 28.2% were of self-reported Black race, 14.4% were ultimately categorized as having head injury, 5.1% as having seizure/epilepsy, and 1.2% as having PTE. Over a median follow-up of 25 (25th to 75th percentile, 17-30) years, 19.9% developed dementia. In fully adjusted models, compared with no head injury and no seizure/epilepsy, PTE was associated with 4.56 (95% CI, 4.49-5.95) times the risk of dementia, while seizure/epilepsy was associated with 2.61 (95% CI, 2.21-3.07) times the risk and head injury with 1.63 (95% CI, 1.47-1.80) times the risk. The risk of dementia associated with PTE was significantly higher than the risk associated with head injury alone and with nontraumatic seizure/epilepsy alone. Results were slightly attenuated in models accounting for the competing risks of mortality and stroke, but patterns of association remained similar. In secondary analyses, the increased dementia risk associated with PTE occurring after first vs second head injury and after mild vs moderate/severe injury was similar.
Conclusions and Relevance
In this community-based cohort, there was an increased risk of dementia associated with PTE that was significantly higher than the risk associated with head injury or seizure/epilepsy alone. These findings provide evidence that PTE is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury.
The blood–brain barrier (BBB) is pivotal in maintaining neuronal physiology within the brain. This review delves into the alterations of the BBB specifically in the context of geriatric epilepsy. We examine how age-related changes in the BBB contribute to the pathogenesis of epilepsy in the elderly and present significant challenges in pharmacotherapy. Subsequently, we evaluate recent advancements in drug delivery methods targeting the BBB, as well as alternative approaches that could bypass the BBB’s restrictive nature. We particularly highlight the use of neurotropic viruses and various synthetic nanoparticles that have been investigated for delivering a range of antiepileptic drugs. Additionally, the advantage and limitation of these diverse delivery methods are discussed. Finally, we analyze the potential efficacy of different drug delivery approaches in the treatment of geriatric epilepsy, aiming to provide insights into more effective management of this condition in the elderly population.
Study objective:
Sleep apnea is associated with unexplained epilepsy in older adults in small studies. We sought to determine the relationship between sleep apnea and additional sleep characteristics and late-onset epilepsy, adjusting for comorbidities, using data from the large, prospective Atherosclerosis Risk in Communities (ARIC) Study cohort.
Methods:
We used Medicare claims to identify cases of late-onset epilepsy (LOE) in ARIC participants. We used polysomnography data from 1309 ARIC participants who also participated in the Sleep Heart Health Study in 1995-1998, and demographic and comorbidity data from ARIC. Later risk of LOE was evaluated using survival analysis with a competing risk of death. We also used survival analysis in 2672 ARIC participants to identify the association between self-reported obstructive sleep apnea (2011-2013), and the risk of subsequent LOE.
Results:
Late-midlife oxygen desaturation to less than 80% during sleep was associated with subsequent development of LOE, adjusted subhazard ratio 3.28 (1.18-9.08), but the apnea-hypopnea index was not related. Participant report of diagnosis of sleep apnea in 2011-2013 was also associated with subsequent LOE, adjusted subhazard ratio 2.59 (1.24-5.39).
Conclusions:
Sleep apnea and oxygen saturation nadir during sleep are associated with LOE, independently of hypertension and other comorbidities. These potentially modifiable risk factors could have large clinical implications for LOE.
Background and objectives:
Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality.
Methods:
We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster.
Results:
From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters.
Significance:
Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone.
Objective
Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous intracranial haemorrhage in older adults. Epilepsy represents a possible sequelae of the disease. To date studies on epilepsy in CAA are missing and the few data available mainly focus on CAA-related inflammation (CAA-ri), the inflammatory form of the disease.
Methods
In this retrospective observational study, we consecutively recruited CAA patients observed in a time span of ten years, collecting demographic, clinical, and instrumental data. Significant baseline characteristics were evaluated as potential risk factors for the development of epilepsy in the CAA population, in the subgroups of CAA-ri and CAA without inflammatory reaction (CAA-nri). The effect of potential risk factors for epilepsy was measured as odds ratio with 95% confidence interval.
Results
Within 96 recruited CAA cases, 33 (34.4%) developed epilepsy during follow-up (median 13.5 months). The prevalent type of seizures was focal (81.3%); 12.1% of the epileptic patients presented status epilepticus and 6.1% developed drug resistant epilepsy. Electroencephalographic traces revealed slow and epileptic discharge activity in the majority of epileptic patients, but also in those without epilepsy. The presence of focal or disseminated cortical superficial siderosis (cSS) was associated with an increased risk of epilepsy in the CAA-nri group, while the association with CAA-ri and epilepsy was present in the overall population.
Significance
Epilepsy is a common manifestation during the course of CAA, where CAA-ri and cSS represent predisposing factors for the development of seizures. These data suggest the importance of a deep characterization of CAA patients, in order to better select those more prone to develop epilepsy.
Epilepsy in the elderly is a complex disease, often underdiagnosed, and inadequately treated. It requires a multi-disciplinary approach and care coordination especially if the patient resides in a nursing facility. Episodes of loss of consciousness falls, or amnestic events in those living in a nursing facility require a detailed description and an urgent assessment to rule out an epileptic seizure. Prompt recognition of seizures and the implementation of treatment protocols in those with recurrent seizures are needed to prevent unnecessary emergency visits. Although there is a myriad of antiseizure medications (ASM) to treat seizures, clinicians should be aware of common interactions, side effects, and changes in pharmacodynamics with age. There is a limited number of ASMs that have been properly studied in clinical trials to assess tolerability and efficacy in the elderly, and an over-reliance on enzyme-inducing ASMs. Strategies to improve the knowledge of health care providers include electronic resources, treatment protocols, and improving awareness of the efficacy, drug-drug interaction, and short-term and long-term monitoring of ASM side effects.
Epileptic seizures in people older than 60 years cause problems in the diagnosis and assignment, especially if the diagnosis of epilepsy has not yet been made, i.e. if epilepsy is newly diagnosed after the age of 60 years. The differential diagnosis, especially of transient CNS ischemia, can be difficult, especially when there are infrequent events or the patients live alone. How often false positive or false negative diagnoses occur has not yet been investigated in large collectives, but in smaller collectives it becomes clear that this is frequent, which also corresponds to own experiences. Diagnosis of epileptic seizures can be very complicated with demented people of higher age, for whom the anamnesis cannot easily be used and one is very dependent on an exact description from others. In old age, attacks with falls and large attacks, even during sleep, are problematic because they are life-threatening. Even if the group of people of higher age does not typically suffer from sudden unexpected death in epilepsy (SUDEP), the consequences of severe seizures are often serious. This article specifically deals with the semiology of seizures in people of higher age, and especially with the differential diagnosis. This is also illustrated using many case studies from personal experience.
Актуальність. Частота розвитку епілептичних нападів у хворих, які перенесли інсульт, коливається в широкому діапазоні — від 3 до понад 60 % [8, 11–15]. Сьогодні в темі постінсультної епілепсії залишаються до кінця не вивченими чимало аспектів цієї проблеми, в тому числі питання щодо призначення протиепілептичних препаратів. Мета дослідження — визначити прогноз розвитку симптоматичної епілепсії після інсульту залежно від прийому антиконвульсантів пацієнтами після першого епілептичного нападу. Матеріали та методи. Комплексно обстежено 1012 пацієнтів (562 чоловіки і 450 жінок) віком від 49 до 90 років, які перенесли ішемічний інсульт протягом 2011–2014 років. Під час проведення аналізу стану всіх 1012 пацієнтів було встановлено, що протягом 6 місяців після перенесеного інсульту хоча б один епілептичний напад було зафіксовано у 161 пацієнта. За типом нападів переважали фокальні (89,9 %; р < 0,001), і лише в 11,1 % пацієнтів були діагностовані первинно-генералізовані епілептичні напади. Результати та обговорення. Для порівняння перебігу стану пацієнтів з інсультом після першого епілептичного нападу нами були сформовані подібні групи: перша (n = 81) і друга (n = 80). У першій групі призначали протиепілептичні препарати після першого епілептичного нападу, у другій групі не призначали. Стан пацієнтів було оцінено через рік після виникнення першого епілептичного нападу. Критеріями оцінки були: наявність другого епілептичного нападу і більше, тобто діагностика симптоматичної постінсультної епілепсії, або взагалі відсутність жодного епілептичного нападу. Відповідно до результатів спостереження, у першій групі, яка приймала антиконвульсанти, протягом року повторні епілептичні напади були зафіксовані у 22 пацієнтів, що становило 27,1 %, тоді як у другій групі, де не проводилося лікування антиконвульсантами, протягом року повторні епілептичні напади були зафіксовані у 43 пацієнтів, що становило 53,75 %. Висновок. Дані результати є підставою для подальших досліджень та можливої рекомендації призначення протиепілептичних препаратів вже після першого епілептичного нападу у пацієнтів, які перенесли інсульт.
Epilepsy is increasing, being more common in older adults, with more than 20% of late-onset cases with unknown aetiology (LOEU). Although epilepsy was associated with cognitive impairment, few studies evaluated the trajectories of cognitive decline in patients with LOEU. The present study aimed at assessing biomarkers of Alzheimer's disease (AD) in patients with LOEU and evaluating their cognitive performance for 12 months. For this study, fifty-five patients diagnosed with LOEU and 21 controls were included. Participants underwent cognitive evaluation and cerebrospinal-fluid (CSF) biomarker analysis (ß-amyloid42 , tau proteins) before starting anti-seizure medication, and then repeated the cognitive evaluation at the 12-month follow-up. A subgroup of LOEU patients and controls also performed 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG PET) before starting anti-seizure medications. At baseline, LOEU patients showed lower Mini-Mental State Examination (MMSE) score, worse cognitive performance in several domains, and lower β-amyloid42 and higher tau proteins CSF levels than controls. Significantly reduced glucose consumption was observed in the right posterior cingulate cortex and left praecuneus areas in LOEU patients than controls, and this finding correlated with memory impairment. In the longitudinal analysis, a significant decrease in MMSE and an increase in verbal fluency scores were found in LOEU patients. These findings evidence that LOEU patients have a significant impairment of cognition, cerebral glucose consumption, and CSF AD biomarkers than controls. Moreover, they showed a progressive global cognitive decline at follow-up, although verbal fluency was preserved. Further studies are needed to better understand the pathophysiological aspects of LOEU and its association with AD.
Neurological disorders as a group are the leading cause of disability worldwide, and their contribution to the overall burden from all health conditions is increasing. Aging of the population, population growth, and the shift from communicable to noncommunicable illness are occurring in many countries and regions, and surveillance of the burden of neurological disorders is required to optimize healthcare planning and resource allocation.
Disease occurs in patterns that reflect the underlying causes or major risk factors. For example, stroke, dementia, and Parkinson's disease occur primarily in older individuals, whereas multiple sclerosis and primary headache disorders have their onset at earlier ages. Although the reasons for these age-dependent differences are largely unknown, some possibilities include immunological responses that are initially aggressive in early adulthood and wane with time, altered vascular responses to dietary and environmental stimuli, and a breakdown in the clearance of misfolded proteins. Stroke has emerged as a common disorder across the developed and developing worlds as the lifespan increases and lifestyle patterns become similar to those in the United States. Multiple sclerosis has been a geographically spreading disease with its onset in northern Europe, in contrast to primary headache disorders, which appear to be rather homogeneous in their distribution. Thus, genetics, as well as environment including dietary patterns, exposure to pollutants, and infections could potentially be the underlying reason for these disorders. Considering the increasing burden of these disorders, it is necessary for epidemiologists and basic researchers to uncover how environmental influences may be driving the changing patterns seen in disease frequency. Such understanding will be helpful in developing treatment protocols and prevention of neurological disorders.
Epileptic seizures in people older than 60 years cause problems in the diagnosis and assignment, especially if the diagnosis of epilepsy has not yet been made, i.e. if epilepsy is newly diagnosed after the age of 60 years. The differential diagnosis, especially of transient CNS ischemia, can be difficult, especially when there are infrequent events or the patients live alone. How often false positive or false negative diagnoses occur has not yet been investigated in large collectives, but in smaller collectives it becomes clear that this is frequent, which also corresponds to own experiences. Diagnosis of epileptic seizures can be very complicated with demented people of higher age, for whom the anamnesis cannot easily be used and one is very dependent on an exact description from others. In old age, attacks with falls and large attacks, even during sleep, are problematic because they are life-threatening. Even if the group of people of higher age does not typically suffer from sudden unexpected death in epilepsy (SUDEP), the consequences of severe seizures are often serious. This article specifically deals with the semiology of seizures in people of higher age, and especially with the differential diagnosis. This is also illustrated using many case studies from personal experience.
Epilepsy is a brain disease characterised by recurrent episodic attacks, epileptic seizures, and their physical, psychiatric, and social consequences. Treating epilepsy in the elderly is challenging because of changes related to ageing, comorbidity, and polypharmacy. New diagnostic criteria of epilepsy will result in a significant increase in the burden of the disease in future epidemiological studies. Most seizures are secondary to cerebrovascular disease, particularly haemorrhage, metabolic abnormalities, and trauma. Seizures in patients with Alzheimer's disease are associated with an earlier onset of cognitive decline. Brain tumours are responsible for 10–30% of seizures in the elderly, typically glioma, meningioma, and brain metastasis. The new Classification of the Epilepsies is a multi‐level classification with three levels: seizure type, epilepsy type, and epilepsy syndrome. The primary goal of care for older adults with epilepsy is to prevent further seizures and maintain a normal lifestyle, free from seizures and with minimal medication side effects.
Background and objectives:
Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals. Head injury is also a risk factor for acquired epilepsy, but the degree to which prior head injury may contribute to LOE is less well understood. Our objective was to determine the association between head injury and subsequent development of LOE.
Methods:
Included were 8,872 participants enrolled in the Atherosclerosis Risk in Communities (ARIC) study with continuous Centers for Medicare Services fee-for-service (FFS) coverage (55.1% women, 21.6% Black). We identified head injuries through 2018 from linked Medicare fee for service claims for inpatient/emergency department care, active surveillance of hospitalizations, and participant self-report. LOE cases through 2018 were identified from linked Medicare FFS claims. We used Cox proportional hazards models to evaluate associations of head injury with LOE, adjusting for demographic, cardiovascular, and lifestyle factors.
Results:
The adjusted hazard ratio (HR) for developing LOE after a history of head injury was 1.88 (95% confidence interval [CI] 1.44-2.43). There was evidence for dose-response associations with greater risk for LOE with increasing number of prior head injuries (HR 1.37, 95% CI 1.01-1.88 for 1 prior head injury and HR 3.55, 95% CI 2.51-5.02 for 2+ prior head injuries, compared to no head injuries) and with more severe head injury (HR 2.53, 95% CI 1.83-3.49 for mild injury and HR 4.90, 95% CI 3.15-7.64 for moderate/severe injury, compared to no head injuries). Associations with LOE were significant for head injuries sustained at older age (age ≥67 years: HR 4.01, 95% CI 2.91-5.54), but not for head injuries sustained at younger age (age < 67 years: HR 0.98, 95% CI 0.68-1.41).
Discussion:
Head injury was associated with increased risk of developing LOE, particularly when head injuries were sustained at an older age, and there was evidence for higher risk for LOE after a greater number of prior head injuries and after more severe head injuries.
Classification of evidence:
This study provides Class I evidence that an increased risk of late-onset epilepsy is associated with head injury and that this risk increases further with multiple and more severe head injuries.
Rationale:
Late-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease.
Methods:
Twenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors.
Results:
Compared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found.
Conclusion:
Patients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.
Dementia is associated with an increased risk of unprovoked seizures and epilepsy, which carry a risk of reduced quality of life and adverse events. The management of seizures and epilepsy in patients with cognitive impairment presents a multitude of challenges for the clinician. The pathology underlying the dementia syndrome may differ and range from neurodegeneration associated with accumulation of beta-amyloid and tau to ischaemic changes, and hence a seizure in a patient with dementia may be considered having a structural cause. Nevertheless, taking the decision to treat or not to treat seizures in dementia patients can be difficult, as the risks of recurrent seizures versus an increased risk of adverse effects of antiepileptic medications have to be weighed up against each other. Moreover, seizures, especially focal onset impaired awareness seizures (previously called complex partial seizures) may be difficult to identify for both patients and caregivers. This may be partly due to lack of awareness of seizures, lack of insight by the patient, and in some instances, such as Lewy body dementia, similarities with other non-epileptic phenomena that are part of the disease. Enquiring about seizure markers should be part of the routine follow-up of patients with dementia and carers should be taught to identify and record episodes of altered awareness. This chapter will present a background on the pathophysiology of seizures and epilepsy in dementia, a guide to diagnosis and differential diagnosis, provide a summary of treatment options, and a discussion on practical issues to consider when choosing an antiepileptic drug, including side effects. These topics will be supplemented by three case scenarios exemplifying these issues.
Objective:
To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.
Methods:
This is an analysis of the prospective Atherosclerosis Risk in Communities (ARIC) study, initiated in 1987-1989 among 15,792 mostly black and white men and women in 4 U.S. communities. We used Centers for Medicare Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67. We used Cox proportional hazards analysis to identify the hazard of mortality associated with LOE and to adjust for demographics and vascular risk factors. We used death certificate data to identify dates and causes of death.
Results:
Analyses included 9090 participants, of whom 678 developed LOE during median 11.5 years of follow-up after age 67. Participants who developed LOE were at an increased hazard of mortality compared to those who did not, with adjusted hazard ratio 2.39 (95% CI 2.12-2.71). We observed excess mortality due to stroke, dementia, neurologic conditions, and end-stage renal disease in participants with compared to without LOE. Only 4 deaths (1.1%) were directly attributed to seizure-related causes.
Conclusions:
Persons who develop LOE are at increased risk of death compared to those without epilepsy, even after adjusting for comorbidities. The majority of this excess mortality is due to stroke and dementia.
Evidence links neuroinflammation to Alzheimer's disease (AD); however, its exact contribution to the onset and progression of the disease is poorly understood. Symptoms of AD can be seen as the tip of an iceberg, consisting of a neuropathological build-up in the brain of extracellular amyloid-β (Aβ) plaques and intraneuronal phosphorylated Tau (pTau) aggregates, which are thought to result from the imbalance between its production and clearance resulting in loss of synaptic health and dysfunctional cortical connectivity.
The glymphatic drainage system, particularly active during sleep, plays a key role in eliminating proteinopathies. Poor sleep can cause hyperexcitability and promote Aβ and tau pathology leading to systemic inflammation. Early neuronal hyperexcitability of γ-aminobutyric acid (GABA)-ergic inhibitory interneurons and impaired inhibitory control of cortical pyramidal neurons are at the crossroad of excitatory/inhibitory imbalance and inflammation. We outline, with a prospective framework, a possible vicious circle linking early chronic short sleep, neuronal hyperexcitability, inflammation and neurodegeneration. Understanding early predictors of AD, through an integrative approach, may promise to reduce attrition in late stages of neuroprotective drug development.
Objective
Epilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU.
Methods
We selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment.
Results
Twenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%).
Significance
Late-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.
Seizures in older adults exist during an extremely common time period of the life cycle. They are often overlooked because they are more likely to be subtle and because of the erroneous perception that seizures are more typically seen in younger adults. Clinicians need to be alert to the fact that seizures are frequent in the older adult population and must be included in the differential diagnosis of older adults with paroxysmal neurological events. Seizures appear slightly differently in the elderly than younger adults as subtle and may not be recalled by the patient. Managing seizures in older adults implies sensitivity to antiseizure medication (ASM). Therefore, starting with low doses of ASM and titrating ASM slowly is a good practice to ensure tolerability. The ultimate goal is balancing seizures and side effects to provide the best quality of life understanding pharmacologic and pharmacokinetic differences in the treatment of older adults with epilepsy.
Seizures affect the lives of 10% of the global population and result in epilepsy in 1 to 2% of people around the world. Current knowledge about etiology, diagnosis, and treatments for epilepsy is constantly evolving. As more is learned, appropriate and updated definitions and classification systems for seizures and epilepsy are of the utmost importance. Without proper definitions and classification, many individuals will be improperly diagnosed and incorrectly treated. It is also essential for research purposes to have proper definitions, so that appropriate populations can be identified and studied. Imprecise definitions, failure to use accepted terminology, or inappropriate use of terminology hamper our ability to study and advance the field of epilepsy. This article begins by discussing the pathophysiology and epidemiology of epilepsy, and then covers the accepted contemporary definitions and classifications of seizures and epilepsies.
Background
Phenytoin (5,5-diphenyl hydantoin) has poor water solubility which results in incomplete oral availability. Other problems associated with the oral and intramuscular administration of phenytoin are gastric irritation and inflammation at the site of injection.
Objective
The purpose of this study was to synthesize mutual amide prodrugs of phenytoin by using amino acids like glycine, L-tryptophan, L-lysine and taurine.
Methods
These prodrugs were synthesized and characterized by Fourier Transform Infrared (FTIR), Proton nuclear magnetic resonance (1 H NMR) and Mass Spectra. Physical and spectral characterization was performed by determination of solubility, maximum wavelength, partition coefficient (log P), ionization constant (pKa), specific (α) and molar rotation (µ), refractive index (n), specific refraction (RS) and molar refraction (RM).
Results
The results obtained from solubility and log P values determination indicated that phenytoin prodrugs can be administered by oral as well as a parenteral route by minimizing the limitations associated with phenytoin. Anticonvulsant activity of prodrugs (4a-4d) was performed by using maximal electroshock (MES) and strychnine induced seizure test on albino mice of either sex weighing 25-30 g in which 4b and 4d were found to have significant anticonvulsant activity for MES and strychnine induced seizure test. In vitro enzymatic hydrolysis study of 4b and 4d was performed on liver, intestinal mucosa and plasma sample of male Sprague Dawley rats weighing 280-300 g in which phenytoin was eluted at 10.13 to 10.68 minute at 220 nm.
Conclusion
The results obtained from the present work showed that amino acid based mutual prodrug strategy can be a promising method to increase the solubility and anticonvulsant activity of phenytoin for the development of anticonvulsant agents.
Objective
To determine the risk of dementia after the development of late-onset epilepsy.
Methods
We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987–1989 with 15,792 mostly black and white men and women from 4 U.S. communities. We identified late-onset epilepsy (LOE; seizures starting at age 67 or later) from linked Medicare claims data. We used a Cox proportional hazards regression model to evaluate associations between LOE and dementia through 2017 as ascertained from neuropsychological testing, interviews, and hospital discharge surveillance; and we used multinomial logistic regression to assess the risk of dementia and mild cognitive impairment in the subset with full neuropsychological assessments available. We adjusted for demographics, and vascular and Alzheimer's disease risk factors.
Results
Of 9,033 ARIC participants with sufficient Medicare coverage data (4,980 [55.1%] female, 1993 [22.1%] black), 671 met the definition of LOE. 279 (41.6%) participants with and 1,408 (16.8%) without LOE developed dementia ( p < 0.001). After a diagnosis of LOE, the adjusted hazard ratio for developing subsequent dementia was 3.05 (95% CI 2.65–3.51). The median time to dementia ascertainment after the onset of LOE was 3.66 years (Q1-Q3 1.28–8.28 years).
Interpretation
The risk of incident dementia is substantially elevated in individuals with LOE. Further work is needed to explore causes for the increased risk of dementia in this growing population.
Objective
To determine the incidence of epilepsy and subsequent 5-year mortality among older adults, as well as characteristics associated with mortality.
Methods
Retrospective cohort study of Medicare beneficiaries age 65 or above with at least 2 years enrollment before January 2009. Incident epilepsy cases were identified in 2009 using ICD-9-CM code-based algorithms; death was assessed through 2014. Cox regression models examined the association between 5-year mortality and incident epilepsy, and whether mortality differed by sociodemographic characteristics or comorbid disorders.
Results
Among the 99,990 of 33,615,037 beneficiaries that developed epilepsy, most were white (79.7%), female (57.3%), urban (80.5%), and without Medicaid (71.3%). The 5-year mortality rate for incident epilepsy was 62.8% (62,838 deaths). In multivariable models, lower mortality was associated with female sex (AHR 0.85, 95% CI: 0.84–0.87), Asian race (AHR 0.82, 95% CI: 0.76–0.88), and Hispanic ethnicity (AHR 0.81, 95% CI: 0.76–0.84). Hazard of death increased with comorbid disease burden (per 1-point increase: AHR 1.27, 95% CI: 1.26–1.27), and Medicaid co-insurance (AHR 1.17, 95% CI: 1.14–1.19). Incident epilepsy was particularly associated with higher mortality when diagnosed after another neurological condition: Parkinson Disease (AHR 1.29, 95% CI: 1.21–1.38), multiple sclerosis (AHR 2.13, 95% CI: 1.79–2.59), dementia (AHR 1.33, 95%CI: 1.31–1.36), traumatic brain injury (AHR 1.55, 95% CI: 1.45–1.66), and stroke/transient ischemic attack (AHR 1.20, 95% CI: 1.18–1.21).
Conclusions
Newly-diagnosed epilepsy is associated with high 5-year mortality among Medicare beneficiaries. Future studies that parse the interplay of effects from underlying disease, race, sex, and poverty on mortality will be critical in the design of learning healthcare systems to reduce premature deaths.
Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin.
We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred.
For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001).
Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.
In a study of patients with focal epilepsy the hypothesis was explored that different measurements of psychopathology are related to specific distributions of cerebral perfusion.
Forty patients had SPECT performed with (99m)Tc-HMPAO. In addition, patients received a psychiatric evaluation with the following psychiatric questionnaires: the Beck depression inventory, the Leyton obsessionality inventory, the Bear-Fedio questionnaire, and the social stress and support interview. Patients were analysed in two groups according to the laterality of the epilepsy. Nine patients were excluded based on poor quality scans (n = 1), unlateralised epilepsy (n = 4), and left or ambidextrous handedness (n = 4).
There were no overall differences between the left and right epilepsy groups on measures of psychopathology. Associations were found between scores on some of the rating scales and regional cerebral blood flow. Specifically, for patients with left sided epilepsy, higher scores on the Beck depression inventory were associated with lower contralateral temporal and bilateral frontal perfusion, and higher occipital perfusion. For patients with right sided epilepsy higher scores on the Leyton obsessionality inventory were associated with increased perfusion in ipsilateral temporal, thalamic, and basal ganglia regions and bilateral frontal regions.
The results do not support the notion that lateralised epileptogenic lesions are associated with different levels of depression, obsessionality, or personality traits. They support the view that certain psychopathological symptom patterns are related to specific regional dysfunctions depending on the laterality of a hemispheric lesion.
We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.
Depression is a frequent psychiatric symptom in epilepsy and has been related to epilepsy of temporal origin, especially of left-sided foci. No study differentiated the precise localization of the epileptogenic lesion within the temporal lobe. Regarding this issue, we evaluated depression assessed by the Beck Depression Inventory in 60 patients with temporal lobe epilepsy, with particular consideration of morphological abnormalities within the temporal lobe (mesial temporal sclerosis (MTS) versus neocortical lesions) and lateralization of the lesion. Multivariate analyses indicated significant higher depression scores in MTS independent of the lateralization of the lesion. Depression was a good indicator for MTS but not vice versa. Hence, MTS can be discussed as a predisposing factor for the development of mood disorders in focal epilepsy.
A history of depression or depressive symptomatology has been reported in up to two-thirds of patients with medically intractable epilepsy, whereas community studies have demonstrated affective disorder only in a quarter of these patients. Depression has been reported peri- and interictally. However, differentiation may be difficult in patients with frequent seizures. Most authors have found no correlation between depression and epilepsy variables. However, complex partial seizures, especially of temporal lobe origin, appear to be etiologic factors, particularly in men with left-sided foci. Depression is also more common in patients treated with polytherapy especially with barbiturates, phenytoin, and vigabatrin. Depression has also been described de novo after temporal lobectomy. Psychosocial factors also play a part, but underlying risk factors (e.g., genetic, endocrine and metabolic) may explain the increased rates of depression in people with epilepsy compared to those with other neurologic and chronic medical conditions. The depression appears to be endogenous. Patients tend to exhibit fewer neurotic traits and more psychotic symptoms such as paranoia, delusions, and persecutory auditory hallucinations. Treatment approaches include psychotherapy, rationalization of antiepileptic drug medication, antidepressant treatment, and ECT. The tricyclic and related antidepressants appear to be epileptogenic, especially in people at high risk (personal or family history of seizures, abnormal pretreatment EEG, brain damage, alcohol or substance abuse/withdrawal and concurrent use of CNS-active medication). Seizures tend to occur early in treatment or after dose increments, especially if rapidly titrated. There is little evidence that the newer antidepressants, e.g., selective serotonin reuptake inhibitors, moclobemide, venlafaxine, or nefazodone are more epileptogenic than placebo.
• Depression is common in epileptics, but few studies of this relationship exist. We investigated the prevalence of depression in comparably disabled outpatients and its phenomenology in psychiatrically hospitalized inpatients. Fifty-five percent of 175 outpatient epileptics and 30% of 70 matched controls reported depression; 30% of epileptics vs 7% of controls reported prior suicide attempts. Epileptics were four times more likely to have been hospitalized for depression than nonepileptics. Twenty depressed epileptic inpatients were characterized by "endogenous" rather than "neurotic" features with more psychotic traits, paranoia, and underlying chronic dysthymia. Sixteen patients had complex partial seizures, and ten of 11 patients had a lateralized electroencephalographic focus lateralized to the left hemisphere. These results suggest a specific epileptic psychosyndrome due to limbic dysfunction.
To determine whether measurement of bone density predicts hip fracture in women, we prospectively studied 9703 nonblack women aged 65 years and older who had measurements of bone mineral density using single-photon absorptiometry in the calcaneus, distal radius, and proximal radius. During an average of 1.6 years of follow-up, 53 hip fractures occurred. The risk of hip fracture was inversely related to bone density at all three measurement sites. After adjusting for age, the relative risk of hip fracture was 1.66 for a decrease of 1 SD in the bone density at the calcaneus (95% confidence interval, 1.22 to 2.26), 1.55 (95% confidence interval, 1.13 to 2.11) at the distal radius, and 1.41 (95% confidence interval, 1.06 to 1.88) at the proximal radius. None of the three measurements was a significantly better predictor of hip fracture than the others. After adjusting for bone mineral density, the risk of hip fracture doubled for each 10-year increase in age (relative risk, 2.09; 95% confidence interval, 1.31 to 3.33). We conclude that decreased bone density in the appendicular skeleton is associated with an increased risk of hip fracture, but this accounts for only part of the age-related increase in risk of hip fracture among older women.
(JAMA. 1990;263:665-668)
Purpose: We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy.
Methods: Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale.
Results: Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance].
Conclusions: The results indicate that the concepts of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.
Purpose: Studies evaluating short‐term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow‐up period and select referral of cases. This study was planned to evaluate short‐term mortality after a first episode of SE.
Methods: We performed a population‐based retrospective cohort study to determine the short‐term mortality following a first episode of SE. Between January 1,1965 and December 31, 1984, we studied all first episodes of a febrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996).
Results: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty‐four deaths (89%) occurred among those with non febrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2–0.9). No effect of duration or seizure type was shown after adjusting for other risk factors.
Conclusions: One out of 5 subjects with SE died within the first 30 days. Short‐term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.
As part of a large community-based study, we retrospectively examined the clinical course of epilepsy in an unselected population of people who had a recent history of seizures or were receiving antiepileptic drugs (AEDs). Clinical information was collected from medical records, and information about psychosocial functioning was obtained by means of postal questionnaires sent to identified subjects. The response rate to the postal questionnaire was 71%. There were some deficiencies in the recording of clinical data, which is not unusual since data were taken from records held by primary physicians rather than from hospital clinics. Nevertheless, findings regarding the clinical course of epilepsy corresponded to those of earlier studies. Fifty-seven percent of the sample had had at least a 2-year seizure-free period and 46% of subjects were currently in a remission of at least 2-year duration. There was a clear relationship between current seizure frequency and levels of anxiety and depression, perceived impact of epilepsy, perceived stigma, and marital and employment status. The relationship of seizure frequency and other clinical variables to psychosocial function was explored by multivariate analysis techniques. The amount of variation in scores on the various measures of function accounted for by the clinical variables was small. The most important predictor was current seizure activity, which was the first variable to enter the regression analyses for six of the eight measures of psychosocial function considered. Age at epilepsy onset also emerged as a significant predictor for depression, stigma, and marital status. In individuals with epilepsy in remission, there was little evidence that psychosocial functioning was associated with length of remission, a finding which may in part reflect the nature of this study population. The results indicate that there are several more important predictors of psychopathology and social dysfunction in epilepsy and suggest several implications for treatment interventions.
A history of depression or depressive symptomatology has been reported in up to two-thirds of patients with medically intractable epilepsy, whereas community studies have demonstrated affective disorder only in a quarter of these patients. Depression has been reported peri- and interictally. However, differentiation may be difficult in patients with frequent seizures. Most authors have found no correlation between depression and epilepsy variables. However, complex partial seizures, especially of temporal lobe origin, appear to be etiologic factors, particularly in men with left-sided foci. Depression is also more common in patients treated with polytherapy especially with barbiturates, phenytoin, and vigabatrin. Depression has also been described de novo after temporal lobectomy. Psychosocial factors also play a part, but underlying risk factors (e.g., genetic, endocrine and metabolic) may explain the increased rates of depression in people with epilepsy compared to those with other neurologic and chronic medical conditions. The depression appears to be endogenous. Patients tend to exhibit fewer neurotic traits and more psychotic symptoms such as paranoia, delusions, and persecutory auditory hallucinations. Treatment approaches include psychotherapy, rationalization of antiepileptic drug medication, antidepressant treatment, and ECT. The tricyclic and related antidepressants appear to be epileptogenic, especially in people at high risk (personal or family history of seizures, abnormal pretreatment EEG, brain damage, alcohol or substance abuse/withdrawal and concurrent use of CNS-active medication). Seizures tend to occur early in treatment or after dose increments, especially if rapidly titrated. There is little evidence that the newer antidepressants, e.g., selective serotonin reuptake inhibitors, moclobemide, venlafaxine, or nefazodone are more epileptogenic than placebo.
Osteoporosis constitutes a major public health problem through its association with fractures at several skeletal sites, most notably the hip, wrist and vertebra. The lifetime risk of hip fracture in White women and men in the UK from age 50 years is 14% and 3%, respectively. These fractures account for considerable mortality, morbidity and healthcare expenditure. Methods of measuring bone density provide useful clinical tools for the assessment of future fracture risk, and a number of preventive and therapeutic strategies are now available to retard bone loss and reduce the incidence of fracture. The most cost-effective use of these pharmacological agents has become a focus for health economic research in osteoporosis. Such research will better define the setting in which various approaches to prevention and treatment are most effective.
Twenty-three patients with complex partial seizures were evaluated with 18F-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions.
The prevalence of epilepsy in Rochester, Minnesota has been determined for a specific date in each of 5 decennial census years. Individuals with a diagnosis of epilepsy (recurrent unprovoked seizures) who were known to have experienced a seizure or who had received antiepileptic medication in the preceding 5 years were considered active prevalence cases. By this definition, the age‐adjusted prevalence per 1,000 population, increased steadily from 2.7 in 1940 to 6.8 in 1980. At each of five prevalence dates, for all prevalence cases, 60% had epilepsy manifest by partial seizures, and 75% had no known etiology. Prevalence was higher for males than females for all except the last prevalence day. After 1950, prevalence tended to increase with advancing age and was highest in the oldest age groups. On the average, the 1980 prevalence cases had epilepsy <10 years and >50% had their first diagnosis in the first 20 years of life.
RÉSUMÉ
La prévalence de ľ epilepsie dans le Comtéde Rochester, dans le Minnesota, a étéévaluée pour une date precise de chacune des 5 années du recensement décennal. Les individus pour lesquels le diagnostic ďepilepsie avait été posé (crises spontanées récurrentes) et qui avaient présenté une crise ou recevaient un traitement antiépileptiques dans les 5 années précédentes, ont été considérés comme des cas de prévalence active. Selon cette définition, la prévalence ajustée pour Page pour 1000 habitants a agumenté constamment de 2.7 en 1940 à 6.8 en 1980. A chacune des 5 dates de prévalence, pour tous les cas, 60% ont présenté une épilepsie se manifestant par des crises partielles, et 75% n'avaient pas ďétiologie connue. La prévalence teAait plus élevée chez les hommes que chez les femmes, sauf lors du dernier jour de prevalence. Aprés 1950, la prévalence tendait à augmenter avec ľâge, elle était la plus forte dans les groupes ďâge élevé En moyenne, les cas de 1980 avaient une epilepsie évoluant depuis moins de 10 ans et plus de 50% avaient une épilepsie diagnos‐tiquée au cours des 20 premières années de vie.
RESUMEN
Se ha determinado la prevalencia de epilepsyía en Rochester, Minnesota, para una fecha especifica en cada uno de los 5 dece‐nios del censo. Individuos con diagnóstico de epilepsía “ataques recurrentes sin provocación” que habían tenido un ataque o recibido medicateón antiepiléptica en los 5 anos precedentes, fueron considerados como casos activos de prevalencia. Segün esta definition la prevalencia ajustada a la edad por 1.000 habitantes se incrementó continuadamente de 2.7 en 1940 a 6.8 en 1980. En cada una de las 5 fechas de prevalencia para todos los casos prevalentes, el 60% tenía epilepsyía manifestada por ataques parciales y el 75% de etiología desconocida. La prevalencia fue mas elevada en varones que en hembras en todos los días de prevalencia excepto el último. Despues de 1950 la prevalencia mostró una tendencia al aumento con incremento de la edad y fue mas elevada en los grupos de mayor edad. Como promedio, los casos de prevalencia en 1980 habían padecido epilepsyía durante menos de 10 años y más del 50% tuvieron el primer diagnóstico en los primeros 20 años de su vida.
ZUSAMMENFASSUNG
Die Praevalenz der Epilepsie in Rochester, Minnesota wurde an einem bestimmten Datum in fünf aufeinanderfolgenden Cen‐sus‐Decenien bestimmt. Personen mit der Diagnose Epilepsie (wiederholte nicht provozierte Anfälle), die einene Anfall erlitten hatten oder Antiepileptika eingenommen hatten wurden als ak‐tive Praevalenz‐Fälle betrachtet. Demnach stieg die altersberei‐nigte Praevalenz für 1000 Einwohner kontinuierlich von 2,7 1940 auf 6,8 1980 an. Zu jedem der fünf Praevalenz‐Daten aller Praevalenz‐Fälle manifestierte sich die Epilepsie in 60% durch Partialanfälle, davon 75% ohne bekannte Atiologie. Die Praevalenz war für Manner hoher als für Frauen während aller Stichtage, ausgenommen des letzten. Nach 1950 stieg die Praevalenz mit zunehmendem Alter leicht an und erreichte ihren höchsten Wert in der ältesten Altersgruppe. Im Durchschnitt hatten 1980 die Praevalen‐Fälle eine Epilepsie für weniger als 10 Jahre. Bei mehr als 50% wurde die Erstdiagnose Epilepsie in den ersten 20 Le‐bensjahren gestellt.
Depression is common in epileptics, but few studies of this relationship exist. We investigated the prevalence of depression in comparably disabled outpatients and its phenomenology in psychiatrically hospitalized inpatients. Fifty-five percent of 175 outpatient epileptics and 30% of 70 matched controls reported depression; 30% of epileptics vs 7% of controls reported prior suicide attempts. Epileptics were four times more likely to have been hospitalized for depression than nonepileptics. Twenty depressed epileptic inpatients were characterized by "endogenous" rather than "neurotic" features with more psychotic traits, paranoia, and underlying chronic dysthymia. Sixteen patients had complex partial seizures, and ten of 11 patients had a lateralized electroencephalographic focus lateralized to the left hemisphere. These results suggest a specific epileptic psychosyndrome due to limbic dysfunction.
We conducted a 10-center, double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults. Patients were randomly assigned to treatment with carbamazepine, phenobarbital, phenytoin, or primidone and were followed for two years or until the drug failed to control seizures or caused unacceptable side effects. Overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbital, and lowest with primidone (P less than 0.002). Differences in failure rates of the drugs were explained primarily by the fact that primidone caused more intolerable acute toxic effects, such as nausea, vomiting, dizziness, and sedation. Decreased libido and impotence were more common in patients given primidone. Phenytoin caused more dysmorphic effects and hypersensitivity. Control of tonic-clonic seizures did not differ significantly with the various drugs. Carbamazepine provided complete control of partial seizures more often than primidone or phenobarbital (P less than 0.03). Overall, carbamazepine and phenytoin are recommended drugs of first choice for single-drug therapy of adults with partial or generalized tonic-clonic seizures or with both.
The incidence of idiopathic/cryptogenic epilepsy and isolated unprovoked seizures has been relatively stable in the population of Rochester, Minnesota, for the 50-year period 1935 through 1984. In each decade, the age-specific rates exhibited a consistent U-shaped pattern of decreasing rates from infancy to age 40-49 and a progressive increase thereafter to a second peak at age 70 years. Males had a 15% higher incidence of cryptogenic unprovoked seizures than females. The most pronounced secular trend was a decrease in the incidence in children aged < 10 years for the first 4 decades of the study; however, this trend was interrupted by a slight rebound in the decade 1975-1984. There has been a progressive decrease in the incidence of cryptogenic unprovoked seizures in individuals aged > or = 50 from 1965 through 1984. This decrease paralleled the decrease in cerebrovascular disease in the community. The decrease in idiopathic unprovoked seizures may be related to a concurrent trend in "silent stroke." Plots and Poisson regression analysis did not show patterns in the incidence of idiopathic unprovoked seizures related to successive birth cohorts. However, significantly lower incidence rates were observed for the 1930-1934 birth cohort, about half that of all others, between the ages of 5 and 54 years.
To examine the relationship of objectively assessed cognitive functioning to self-reported quality of life.
Correlational, multiple regression, and factor analytic comparisons of a new self-report quality of life inventory with neuropsychological tests of cognition and mood.
Two hundred fifty-seven patients with epilepsy.
Twenty-five epilepsy centers and neurology clinics across the United States.
A recently developed self-report (ie, Quality of Life in Epilepsy-89 inventory) and objective tests of memory, verbal abilities, spatial functions, psychomotor and cognitive processing speed, cognitive flexibility, and mood.
Factors that assessed mood, psychomotor speed, verbal memory, and language correlated significantly with selected scales of the Quality of Life in Epilepsy-89 inventory (P < .0001) and were predictive of overall quality of life (P < .002 to P < .0001). The mood factor showed the highest correlations (r = -.20 to r = -.73) and was the strongest predictor of quality of life in regression analyses (46.7% explained variance, P < .0001).
Mood may be adversely affected by diminished quality of life, or perceived quality of life may be affected by mood disturbance. Quantitative quality of life assessments can be used in conjunction with formal neuropsychological testing of mood and cognition when evaluating patients with epilepsy.
We determined the incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 through 1984. The age-adjusted incidence rates for 1955-1984, the period of most complete case ascertainment, was 39.0/100,000 person-years (United States 1970 population as standard). The age-adjusted incidence was considerably higher in men: 52.0 as compared with 29.5 in women. The 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan approaches that of developing epilepsy. The major causes of acute symptomatic seizures were traumatic brain injury, cerebrovascular disease, drug withdrawal, and CNS infections. Each type of acute symptomatic seizure has age, gender, and time period patterns that reflect the occurrence of the underlying cause.
To examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children.
Axial (second, third, and fourth lumbar vertebrae) and appendicular (distal third of radius) bone mineral density was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26 children with uncomplicated idiopathic epilepsy treated with either carbamazepine (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and patients were similar with respect to age, race (all white), and geographic area, and had no dietary restrictions, neurologic impairment, or physical handicaps.
Subjects were seizure-free for more than 6 months on a regimen of carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/- 2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium intake was similar in control and treated groups. After correction for gender and age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005) reduction in bone mineral density at the axial and appendicular sites, respectively. The reduction in bone mineral density increased with the duration of valproate therapy. Carbamazepine did not significantly reduce bone mineral density.
Valproate montherapy, but not carbamazepine therapy, significantly reduces axial and appendicular bone mineral density in children with idiopathic epilepsy and may increase their risk of osteoporotic fractures.
In order to assess the bone changes in the subjects receiving anti-epileptic drugs (AEDs), bone mineral densities (BMDs) of the arms, legs, ribs, pelvis, spine, and the whole body were scanned in 78 epileptic children and in 78 controls using dual photon absorptiometry. The study subjects were classified according to the duration of the monotherapy with phenobarbital (PB) or phenytoin (PHT); those who received AEDs for less than 12 months as Group I, for 13-23 months as Group II, and for 24 months as Group III. Group III was subclassified according to the kind of AEDs administered, into those receiving PB as Group IIIp, and those receiving PHT as Group IIId. There was no significant differences in the BMDs of each area, when compared to each control in Groups I and II. In Group III, there were significant differences in ribs and spine, according to the duration of administration. In Group IIIp, there was a significant difference in ribs and spine, and, in Group IIId, there was a significant difference in most of the areas. These results show that the measurement of BMDs in the ribs and spine is necessary for the early detection of subtle bone loss, and it is recommended that vitamin D be administered to children with epilepsy receiving AEDs over 24 months.
We tested the a priori hypothesis that hypertension can lead to seizures through vascular brain damage that might or might not involve manifest stroke. A case-control study with 227 patients admitted for a first unprovoked seizure and 294 acute surgical controls was carried out at Harlem Hospital Center, New York City, between 1981 and 1984. History of hypertension was significantly associated with unprovoked seizures, even after adjustment for antecedent stroke and other potential confounders (adjusted odds ratio [OR] = 1.57; 95% confidence limit [CL], 1.0 to 2.44). There was marked synergism between history of stroke and history of hypertension; subjects with a history of both had a fourfold increase in seizure risk compared with subjects with neither (adjusted OR = 4.07; 95% CL, 1.50 to 11.0). In these data, history of hypertension appears to be an independent risk factor for new-onset unprovoked seizures, especially, but not only, in conjunction with a history of stroke.
During a 20-month period, an attempt was made to find all children with unprovoked non-febrile seizures. The first attendance and incidence rates were 95 and 89/100,000, respectively, in the age group 0-15 years. These figures are lower than those found 10 years earlier in the same area. The highest incidence was during the first year of life and there was a higher proportion of girls (male:female ratio 1:1.4). Generalized seizures dominated in the first year of life. The incidence of benign childhood epilepsy with centro-temporal spikes was 10.7/100,000 and was the most common epilepsy syndrome found. The incidence of partial seizures increased with age up to the age of 10 years. One in 10 children had a history of febrile convulsions.
The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Age-adjusted incidence of epilepsy was 44 per 100,000 person-years. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged > or = 75 years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age-adjusted incidence of all unprovoked seizures was 61 per 100,000 person-years. Age- and gender-specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly.
In a population-based prospective study of epileptic seizures in adult s aged > 17 years, we identified 563 patients with possible seizures in a period of 34 months. Seizures were unprovoked in 160 patients, an incidence of 56 in 100,000 person-years. There was no difference in incidence between sexes. Age-specific incidences of unprovoked seizures increased sharply in men from age 60 years and in women from age 70 years. The incidence of unprovoked seizures in those aged > 65 years was 139 (men 166, women 116). The cumulative incidence of unprovoked seizures between the ages of 17 and 84 years was 4.6%. The proportion with an identified presumptive cause for unprovoked seizures increased with advancing age. A presumed etiology was identified in 77% of persons aged > 60 years. Stroke was the most common etiology, detected in 30% (incidence 16) and in 45% at ages > 60 years. Tumors were detected in 11% (incidence 6) and Alzheimer's disease was detected in 7% (incidence 4). Eighteen percent of patients were demented. Unprovoked seizures were partial in 68% of cases (incidence 38), and generalized in 16% (incidence 9). Another 13% of patients had generalized seizures, but seizure onset was not witnessed (incidence 7). In 16%, there was a delay of > 1 year from the first unprovoked seizure to initial diagnosis.
We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0; 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy.
We tested the hypothesis that dementia increases the risk of unprovoked seizure among adults. Partial- and generalized-onset seizures were considered together and separately. Additionally, we explored whether the increased risk was restricted to Alzheimer's disease (AD), as previously shown.
Subjects in this population-based case-control study were 145 incident cases of first unprovoked seizure (without prior stroke, CNS infection, brain tumor, head trauma, mental retardation, or cerebral palsy) aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow-up. Using the records-linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, information on dementia prior to onset of unprovoked seizure. Subjects were classified as having dementia if they met ad hoc criteria equivalent to those in the DSM-III. AD was distinguished from other dementias.
Both a diagnosis of AD and a diagnosis of other dementia were associated with at least a six-fold increased risk of unprovoked seizure when controlling for age, sex, and length of medical follow-up in Rochester. There was no difference in risk when comparing generalized-onset seizures with partial-onset seizures.
In the absence of other prior neurologic insult, both AD and other dementias increase the risk of generalized- and partial-onset unprovoked seizures.
We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy.
Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale.
Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance].
The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.
This report presents the initial analysis of a prospective, population-based study of status epilepticus (SE) in the city of Richmond, Virginia. The incidence of SE was 41 patients per year per 100,000 population. The frequency of total SE episodes was 50 per year per 100,000 population. The mortality rate for the population was 22%, 3% for children and 26% for adults. Evaluation of the seizure types for adult and pediatric patients demonstrated that both partial and generalized SE occur with a high frequency in these populations. Based on the incidence of SE actually determined in Richmond, Virginia, we project 126,000 to 195,000 SE events with 22,200 to 42,000 deaths per year in the United States. The majority of SE patients had no history of epilepsy. These results indicate that SE is a common neurologic emergency.
Management of epilepsy in the elderly requires understanding of the unique biochemical and pharmacologic characteristics of this patient population. Accurate assessment of seizures and identification of epilepsy syndromes, thorough neurologic assessment to define etiology, and comprehensive evaluation of the patient's health and living situation are necessary for informed management decisions. Challenges to treatment include concomitant diseases, polypharmacy with accompanying drug interactions, and changes in physiology, such as changes in renal clearance and hepatic function than alter drug absorption, protein binding, metabolism, and elimination. Elderly patients with declining intellectual function, motor impairment, or altered sensory function may be especially susceptible to dose-related CNS side effects of antiepileptic drugs (AEDs). Drugs prescribed for concomitant illnesses such as hypertension, cardiovascular disease, infections, behavioral problems, and gastrointestinal disturbances may alter absorption, distribution, and metabolism of AEDs, with an adverse impact on efficacy and increased occurrence of adverse effects. The AEDs may induce metabolism of other drugs, resulting in decline in target response. Addition of an AED to an elderly patient's medical regimen requires careful review of all prescribed drugs. Optimal care of elderly patients with epilepsy includes use of free drug levels to monitor AED concentrations, careful dose selection, and sensitivity to the social problems that may occur in this population.
Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE.
We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied all first episodes of afebrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996).
Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of duration or seizure type was shown after adjusting for other risk factors.
One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.
To describe the prescribing and use of antiepileptic drug (AED) therapy in nursing facility residents.
A retrospective, multicenter drug use evaluation.
A total of 85 nursing facilities (average size, 119 beds) in five states.
1132 residents of the total 10,168 residents screened were prescribed at least one AED.
Demographic information, primary indication for AED, comorbid conditions, prescribing physician's specialty, concomitant medications, and AED dosage regimen information were collected. Laboratory tests obtained in the most recent 6 months and seizure occurrence and seizure-related diagnostic assessments made in the most recent 3 months were also recorded.
Of 1132 residents receiving AED therapy, 892 (78.8%) were prescribed AED therapy for a seizure-related diagnosis although 86% of seizure types were unspecified. Another 215 residents (19.0%) were prescribed AEDs for nonseizure diagnoses, and 25 (2.2%) had no indication for AED therapy. AEDs most frequently prescribed were phenytoin (56.8%), carbamazepine (23.0%), phenobarbital (15.6%), and valproic acid (13.1%). For residents with a seizure diagnosis, the most frequently prescribed monotherapy agents were phenytoin (52.0%), carbamazepine (12.2%), and phenobarbitol (7.1%). Almost 25% of residents with a seizure diagnosis took a combination of AEDs; more than 50% of all combinations included phenobarbital. About 9% of residents with a seizure diagnosis had one or more documented seizures during a 3-month review period.
Among the substantial percentage of residents treated with AEDs, the lack of diagnosis of seizure type has serious implications for the choice of AED therapy. Opportunities exist for prescribing physicians, consultant pharmacists, and nursing staff to improve the medical management of nursing facility residents with seizures and of others receiving AEDs.
We assessed the effects of sodium valproate and carbamazepine monotherapy on bone mineral density (BMD) in children. BMD at the lumbar vertebrae (L1-L4) and radius-ulna was measured by the dual-energy x-ray absorptiometry (DEXA) method in 19 children (9 girls, 10 boys) with uncomplicated epilepsy and in 57 healthy children (28 girls, 29 boys), between the ages of 6 and 12 years. The study patients had been receiving either sodium valproate (n = 13) or carbamazepine (n = 6) monotherapy for more than 6 months. There were no significant differences between the control and study patients in age, height, weight, physical activity, or of serum concentrations of calcium, phosphate, and transaminases (aspartate aminotransferase, alanine aminotransferase). However, the serum alkaline phosphatase concentration was greater in the patient group as compared with the control group. BMD values were lower in girl patients (L1-L4; 0.497 +/- 0.08 vs 0.566 +/- 0.07 g/cm2, p < 0.05), but not in boys (0.534 +/- 0.06 vs 0.530 +/- 0.08 g/cm2). While BMD reduction was 8% in valproate therapy (midregion of radius-ulna; 0.287 +/- 0.03 vs 0.312 +/- 0.04 g/cm2, p < 0.04), it was reduced only 4.5% in the carbamazepine-treated group (0.298 +/- 0.01 vs 0.312 +/- 0.04 g/cm2, statistically not significant), although the mean durations of monotherapy with valproate (1.8 +/- 0.7 years) and carbamazepine (1.7 +/- 0.8 years) were similar. Thus decreased bone mineralization was observed in children with epilepsy, treated with sodium valproate even though treatment was for a rather short time.
To study fracture rates and risk factors for fractures in non-institutionalized patients with epilepsy.
Historical follow-up. Self-administered questionnaires were issued to 755 patients with epilepsy (ICD 10: G40.0 to G40.9) and 1000 randomly selected controls from the background population.
A total of 345 patients (median age: 45, range 17-80 years) and 654 control subjects (median age: 43, range 19-93 years) returned the questionnaire. Before epilepsy was diagnosed there was no difference in overall fracture rate between patients and controls (RR = 1.0, 95% CI: 0.8-1.3). After the diagnosis the overall fracture rate was significantly higher in the patients (RR = 2.0, 95% CI: 1.6-2.5). Fractures of the spine, forearms, femurs, lower legs, and feet and toes were significantly increased. Fractures related to seizures accounted for 33.9% (95% CI: 25.3-43.5%) of all fractures. After elimination of seizure related fractures the increase in fracture frequency was only borderline significant: RR = 1.3 (95% CI: 1.0-1.7, P = 0.042). No difference in fracture energy between patients and controls was observed (low energy fractures: 1.7/1.4%, medium energy fractures: 59.8/52.0%, and high energy fractures: 38.3/46.6%). Use of phenytoin (OR = 2.4, 95% CI: 1.1-5.4) and a family fracture history (OR = 2.4, 95% CI: 1.3-4.6) was associated with an increased fracture risk.
Fractures were more common in epileptics than in controls especially among users of phenytoin. Most of the increase in fracture frequency was related to seizures and not to low bone biomechanical competence.
Depression is a common occurrence among epileptic patients and constitutes, along with anxiety disorders, the most frequent psychiatric condition in these patients. The relationship between depression and epilepsy is two-directional, because patients with major depression also have a higher frequency of epilepsy. In epileptic patients, depressive disorders can present as unipolar, bipolar, or dysthymic disorders. More characteristically, however, they present as an atypical depression, which can often go unrecognized for long periods of time. In the diagnostic evaluation of these patients, clinicians must rule out the possibility that the depressive disorder resulted from the administration of antiepileptic drugs (AEDs; e.g., barbiturates) or from the discontinuation of an AED with mood-stabilizing properties that were masking an underlying affective disorder. Although antidepressant drugs have been used in epileptic patients for a long time, to date there has only been one controlled study. The antidepressants of the family of selective serotonin reuptake inhibitors (SSRIs) should be considered as initial therapy for depressive disorders in these patients.
This case-controlled study explored the relationship between bone mineral density (BMD) and long-term treatment with antiepileptic drugs (AEDs) in older adults with epilepsy. Seventy-eight patients (47 post-menopausal females, 31 males, aged 47-76 years) with epilepsy participated in the study. Each had only ever received treatment with either enzyme-inducing (n = 52) or non-inducing (n = 26) AEDs. Individuals were matched for age, sex, height and weight with a drug-naive control. All patients underwent bone densitometry at the lumbar spine and femoral neck and had blood sampling and urine collected for a range of bone markers. Male patients had lower BMD than controls at the lumbar spine (P < 0.01) and neck of the femur (P < 0.005). Female patients had significantly reduced bone density at the femoral neck (P < 0.05) only. AED usage was independently associated with an overall reduction in bone density at femoral sites and contributed to just over 5% of the variance at the femoral neck. Duration of treatment and type of AED were not independent factors for reduction in BMD. This case-controlled study supports the hypothesis that long-term AED therapy is an independent risk factor for reduced BMD in epileptic patients. Adults receiving treatment for epilepsy are at higher risk of osteoporosis and should be offered bone densitometry.
The purpose of this article is to review the topic of interictal psychiatric comorbidity among adult patients with chronic epilepsy, focusing specifically on those studies that have used contemporary psychiatric nosology. Five specific issues are addressed: (a) the risk and predominant type(s) of psychiatric comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric disorders impose upon patients with chronic epilepsy, (d) the etiology of these disorders, and (e) strategies for treatment. Current appreciation for these issues in epilepsy is contrasted to related fields (e.g., primary care, psychiatry, and epidemiology), where considerable attention has been devoted to the identification, consequences, and treatment of psychiatric comorbidity. The issue of psychiatric comorbidity in epilepsy is reviewed with the aim of identifying a clinical and research agenda that will advance understanding of at least one important psychiatric condition associated with epilepsy-namely, major depression.
To determine the incidence, risk factors, and case fatality rate of status epilepticus (SE) in the French-speaking part of Switzerland.
Between October 1, 1997 and September 30, 1998 all cases of SE referred to all the hospitals in the six cantons of the French-speaking part of Switzerland were identified by physicians working in emergency rooms, intensive care units, and electroencephalography departments; neurologists; and pediatricians from all hospitals in the area. Each case was validated and classified according to seizure type and etiology.
Over 1 year, 172 cases were identified, of whom 74 had a history of epilepsy (42.4%). The crude and standardized annual incidence rate were 9.9/100,000 (95% CI, 8.4 to 11.4) and 10.3/100,000 (95% CI, 8.7 to 11.9). The incidence rate was higher among children < 1 year of age and adults > 65 years, and among men than women. There were 108 cases of acute symptomatic SE (incidence: 6.2 per 1000), 49 cases of remote symptomatic SE, and 15 cases of unknown etiology. Case fatality rate was 7.6%.
The standardized incidence rate of SE in the French-speaking part of Switzerland was lower than that reported in Rochester, MN (18.3/100,000) and in the white population of Richmond, VA (20/100,000). The discrepancy may stem from the lack of a homogeneous, rigorous, and pragmatic definition of SE and the efficient management of acute repetitive seizures in this area.
To determine the incidence and case-fatality rate of status epilepticus (SE) in adults in Hessen, Germany, we performed a prospective, population-based study from July 1997 through June 1999.
All adult patients residing within the zip-code area 35 (area-35) with SE were included. Area-35 had 743.285 adult inhabitants, including 123.353 adult inhabitants of the primary service area of the University Hospital Marburg (PS-area). Patients were reported by 16 hospitals in the area and were prospectively identified and carefully reviewed within 5 days by one of the authors. Based on the crude annual incidence of SE and a rate of underascertainment of 10% determined for the PS-area, the corrected, age-adjusted incidence of SE in area 35, more representative of the population of Germany, was calculated.
The crude annual incidence in the PS-area was 15.8/100,000 [95% confidence interval (CI), 11.2-21.6]. The calculated, corrected, age-adjusted incidence of SE in area 35 was 17.1/100,000. It was higher for men compared with women (26.1 vs. 13.7) and for those aged 60 years and older (54.5 vs. 4.2/100,000, p < 0.0001). The etiology was mainly remote symptomatic due to cerebrovascular disease. Epilepsy was previously diagnosed in only 50% of the patients. The case-fatality rate was 9.3%.
Based on our data, at least 14,000 patients would be affected by SE in Germany, associated with approximately 1,300 deaths annually. The incidence of SE in Germany is similar to that found in the white United States population. Furthermore, this study confirms the higher incidence of SE in male patients and in the elderly population. This may be due to a higher incidence of cerebrovascular disease in these subpopulations.
Although hip fracture is one of the most common causes of acute immobilization in elderly patients, little is known about the influence of immobilization on changes in bone and calcium metabolism following this event. We therefore compared serum biochemical indices of bone and calcium metabolism in 20 elderly subjects with hip fracture with those measured in 20 healthy age-matched controls. Rankin scores, a measure of functional dependence with 0 representing independence and 5 representing total dependence, were assigned. We also examined serial changes in these biochemical indices from shortly following the fracture to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-[OH]2D) were measured. One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]2D were depressed. Rankin score (mean: 4.4) correlated positively with ICTP and negatively with BGP at this time. At 2 months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]2D were less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2. Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium and BGP returning to normal. We concluded that increased bone resorption, and decreased bone formation, and hypercalcemia are present by 1 week following the hip fracture, and some resorption increase persists for at least 3 months. These changes could explain in part the high risk of another hip fracture.
Bone loss and hypovitaminosis D are reported in patients taking antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA).
To assess the relationship of VPA to bone mass and calcium metabolism in 40 adults with epilepsy on long-term VPA monotherapy, 40 age- and sex-matched epileptic patients taking phenytoin (PHT), and 40 healthy control subjects. Bone mineral density (BMD) of the second metacarpal was determined as T- and Z-scores.
BMD reduction from control values was 14% (12% in men, 16% in women) with VPA and 13% (12% in men, 15% in women) with PHT. Among patients on VPA, nine (23%) had T-scores below -2.5 SD, suggesting osteoporosis; 15 (37%) had T-scores between -1 and -2.5 SD, suggesting osteopenia. Serum concentrations of calcium were significantly higher with VPA than in PHT or control groups. Serum concentrations of bone Gla protein (a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) associated with either drug significantly exceeded control values. Z-scores for BMD in the VPA group correlated negatively with calcium and ICTP. High ICTP correlated positively with ionized calcium, implying that increased bone resorption caused the latter.
Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD.
Status epilepticus (SE) is a medical emergency associated with a high mortality. Clinical series have suggested that mortality after SE has decreased. No studies have systematically examined trends in incidence, mortality, and case fatality after SE in a well-defined population.
All first episodes of SE receiving medical attention between January 1, 1935, and December 31, 1984, were ascertained through the Rochester Epidemiology Project Records-Linkage System and followed up until death or study termination (February 1, 1996). We calculated incidence rates in the 50-year period (1935-1984), while we considered mortality and case-fatality in the last 30-year period (1955-1984).
Incidence of SE increased over time to 18.1/100,000 (1975 through 1984). The increase was related to an increased incidence in the elderly and to the advent of myoclonic SE after cardiac arrest, a condition not seen in the early decades. In the last decade, approximately 16% of the incidence was due to myoclonic SE. The mortality rates increased from 3.6 per year in the decade 1955-1965 to 4.0/100,000 per year between 1975 and 1984. The 30-day case-fatality (CF) was unchanged, although a trend toward improvement was shown after excluding myoclonic SE.
Incidence and mortality rates of SE have increased in the last 30 years. Case fatality remained the same. The increased incidence and mortality are due to the occurrence in the last decade of myoclonic SE after cardiac arrest. The mortality in the elderly was twice that of the youngest age group, across all study periods. Changes in the age and cause distribution of SE over time are responsible for the stable survivorship. There is improvement in survivorship in the last decade when myoclonic SE is excluded.
Few population-based studies of status epilepticus have been performed in the United States.
To determine the incidence, case fatality, and demographics of generalized convulsive status epilepticus (GCSE) in the state of California.
Using a state-wide hospital discharge database, the authors identified all hospitalizations from 1991 through 1998 with a discharge diagnosis of convulsive status epilepticus. They identified the first admission for each individual to estimate the incidence of GCSE. In-hospital case fatality rates were calculated, and multivariate analysis was performed to determine predictors of death during hospitalization. Secondary diagnoses were analyzed by retrieving all discharge diagnoses accompanying the diagnosis of GCSE.
The incidence rate of GCSE was 6.2/100,000 population and fell by 42% between the years 1991 and 1998 from 8.5 to 4.9/100,000. The rate of GCSE was highest among children under the age of 5 (7.5/100,000) and among the elderly (22.3/100,000). Blacks also demonstrated a relatively high incidence of GCSE (13.4/100,000). The case fatality for incident admissions was 10.7%, with increasing age being the only significant predictor in multivariate analysis. Case fatality was highest in patients who also carried a diagnosis of anoxia, CNS infection, or stroke.
The incidence of GCSE requiring hospitalization has fallen over the last decade and is lower than that reported in previous studies. The case fatality is also lower than that reported previously. Further studies are needed to determine the cause of this decline in incidence and mortality of GCSE.
Article abstract Epilepsy is a chronic condition with complex effects on a person's social, vocational, and psychological function. Recent advances in methods and instruments to assess subjective health status and patient preferences have provided important data on health outcomes in epilepsy. For many patients that do not respond to initial trials of antiepileptic medications, epilepsy surgery is a treatment alternative that offers the possibility of complete control of seizures and improved quality of life. Adverse medication effects and depression are readily identified by systematic use of reliable and valid instruments, and may be the most important negative influences on a person's perception of their current health status. Adequate education regarding relative risks of recurrent seizures compared to surgery, systematic screening for adverse medication effects and subsequent selection of appropriate antiepileptic drugs, and identification and treatment of depression should offer substantial improvement in overall health of persons with epilepsy.
Long-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density.
A cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy-vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients.
Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide.
Epilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.
Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures.
To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs.
We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time.
Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment.
Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs.