Epilepsy is one of the stigmatizing afflictions still common in the developing countries. It is a condition that can affect anyone at any time. Epilepsy is not a “disease” in itself, but is the outward manifestation of other underlying conditions. The cause is often unidentifiable, although modern imaging techniques are rapidly increasing the ability to identify the cause in more patients. Further, epilepsy is not a singular disease entity but a variety of disorders reflecting underlying brain dysfunction that may result from many different causes. These conditions may cause other disorders – as consequences – that manifest as co-existence illnesses. On the other hand, the co-existence illnesses may precede or occur simultaneously with the diagnosis of epilepsy.
In chronic condition, such as epilepsy, the co-existence of more than one illness in a patient is the rule rather than the exception. The co-existence of illness is referred to as co-morbidity if the analysis focuses on an index condition (i.e., the co-morbidity of epilepsy) or as multi-morbidity if no particular condition is targeted (i.e., a group of conditions affecting and individual patient). Studies from developed countries, involving diverse epilepsy population and using diverse methodologies, consistently report a higher prevalence of somatic and psychiatric conditions in individuals with epilepsy than in the general population. Men and women with epilepsy have a two- to five-fold increase in the occurrence of conditions, such as migraine, cerebrovascular and cardiovascular disorders, gastro-intestinal disorders, pulmonary disorders, dementia, chronic fatigue, mood disorders, anxiety, and personality disorders.
Epilepsy is associated with an increased risk of mortality. Death may be related to an underlying brain disease such as a tumor or infection, seizures in dangerous circumstances (leading to drowning, burns or head injury), status epilepticus, sudden and unexplained causes or possible respiratory or cardio-respiratory arrest during a seizure, and suicide. Meanwhile, remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.
The co-morbidity of epilepsy is an important issue to be discussed since – intuitively – the co-existence of more than one chronic condition should result in additive burdens on health. Proper understanding on co-morbidity will improve the management and service quality of epileptic patients. In addition, mortality rate in the long term is still higher that of the general population. Effort to decrease the mortality risk is an integral part of the management of epileptic patients.
Co-morbid condition may precede, occur simultaneously with, or follow the diagnosis of epilepsy. The temporal occurrence of co-morbid conditions is of importance to understanding causal associations and common or shared disease mechanisms. A review of reports of the temporal association of co-morbid conditions with epilepsy reveals that a history of various conditions is associated with an increased risk for developing epilepsy. Among children, a history of attention deficit hyperactivity disorder, predominantly the inattentive type, is associated with an increased risk for epilepsy.
The majority of patients with epilepsy suffer from one or more psychiatric or somatic co-morbid conditions, whose nature and prevalence vary with age and socio-demographic factors. In these patients, co-morbid conditions have a major adverse effect on overall health and quality of life and substantially increase health care costs. Although there is an understanding of epidemiological aspects of the co-morbidity of epilepsy, little is known about causal relationship, clinical interventions to prevent co-morbidities, or the management of patients with multiple co-existing conditions. Both the effects of epilepsy therapies on co-morbidities and the effects of co-morbidities on the efficacy of epilepsy treatments warrant further study.
Patients with epilepsy have been thought to have a higher risk of illness than the general population, but co-morbidity in epilepsy has been investigated in few population-based prevalence or analytic studies. Other clinical conditions and disabilities were reported by 47% of adults with epilepsy in Sweden, with psychiatric, cardiovascular, pulmonary, systemic, and renal diseases in decreasing order. Lifetime mental and gastric disorders were reported by 7% and 3% of adults with childhood-onset epilepsy in Czech Republic. In Finland, somatic co-morbidity was found in 84-95% of patients with childhood-onset epilepsy and 67-74% of controls. In a multi-center European cohort study of children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy, one or more illness at entry in 30% of cases compared with 17% of age- and sex-matched controls.
A population-based study on 8057 adults in Georgia and Tennessee USA revealed a lifetime epilepsy prevalence of 2.1% in this population. A structured interview revealed that those with epilepsy had significantly worse self-reported fair or poor health status (39% vs 17% in adults without epilepsy), significantly greater cigarette smoking (38.8% vs 24.9% in other adults), and high rates of obesity (34.1% vs 23.7% in adults without epilepsy). Large percentages of adults with epilepsy reported currently symptomatic asthma and recent joint pain. Adults with epilepsy had lower educational attainment and lower household incomes, but a higher rate of medical insurance coverage, than did other adults. This type of population-based survey can serve to identify health disparities, and unmet health care needs in individuals with epilepsy.
There are four perspectives of psychiatry in every patient with epilepsy. Those are biological dysfunction involving the nervous system, human traits that vary from individual to individual along a continuum, behavioral presentations, and life-story perspectives. Behavioral presentations in epilepsy can be caused by the epilepsy itself, anti-epileptic drugs, underlying brain dysfunction, personal/parental reaction or response to having epilepsy, and idiopathic.10 The followings examples of psychiatric perspectives such as behavioral problems, depression, autism, ADHD, and psychosis, will be discussed briefly.
- Behavioral problems
- Just epilepsy is a heterogeneous disorder with multiple etiologies, seizure types and syndromes, and variable degrees of seizure control, there are multiple factors that influence the risk of psychopathology in children with epilepsy. Factors to consider in assessing the prevalence of behavioral problems include demographic variables, neurological variables, seizure variables, therapy, and psychosocial variables. Behavioral and emotional problems are major concern for children with epilepsy. Behavioral problems, such as the inattentive form of attention-deficit hyperactivity disorder (ADHD), anxiety, and depression, are common in children and adolescents with epilepsy and especially associated with central nervous system damage, family dysfunction, and severe seizures.
- The behavioral problems often are not recognized or are not treated. In one study of children with epilepsy and normal intelligence, 61% of the children had a psychiatric diagnosis based on DSM-IV criteria, but only 33% of the children received mental health treatment.
- Behavioral problems in epileptic patients may be a hidden co-morbidity. The clinicians should pay extra-attention to this condition, particularly while taking anamnesis. The history taking should also be addressed to the patients’ family.
- Additionally, several population-based studies have shown that a history of major depression is associated with an increased for developing epilepsy. Clues regarding the underlying causes of these association have been limited, yet it is unlikely that they are a mere co-incidence; further clarification is needed to elucidate shared pathogenesis or shared genetic susceptibility.
- Depression is a common but often overlooked problem in epilepsy. Children more often present with irritability, withdrawal, somatic complaints, and trouble sleeping. Difficulties with concentration may lead to school failure. Adolescents may have similar complaints but also develop hopelessness, guilt, and suicidal ideation. A family history of mood disorder may be an important clue to the diagnosis of depression in children with epilepsy. In the differential diagnosis of depression and childhood epilepsy, as with attention disorders, the psychiatric effect of anti-epileptic drugs (AEDs) should be considered. Phenobarbital has been associated with depression and an increased risk of suicide. Newer AEDs whose mechanism is GABA-ergic, such as levetiracetam, topiramate, tiagabine, and zonisamide, have caused depressive symptoms.
- It should be kept on mind that depression may present simultaneously with the epileptic events. However, depression in epileptic patients may be caused by certain anti-epileptic drugs or as a result of the epilepsy itself.
- Epilepsy occurs in 10-30% of individuals with autism. This association was mentioned in the first description of autism by Kanner. However, the association between autism and specific epileptiform electro-encephalography (EEG) abnormalities is not firmly established; either is the prevalence of epileptiform abnormalities in the broader range of pervasive developmental disorders (PDDs).
- Autism is associated with epilepsy in early childhood, with evidence suggesting that individuals with both autism and more severe cognitive impairment are at higher risk. However, the incidence of an abnormal EEG and / or epilepsy in the full range of PDDs is nor well defined. A retrospective study on 56 children diagnosed with PDD – not otherwise specified, autism, or Asperger syndrome revealed 40% of children with autism were diagnosed with epilepsy. Abnormal EEG and epilepsy occurred at significantly higher rates in children in the more impaired range of the autism spectrum (p less than 0.05). These findings suggest that the use of neurological investigative techniques such as EEG should be a consequence of careful clinical evaluation and should be considered routinely during evaluation of more impaired individuals.
- Epilepsy should be suspected in children with autism spectrum who have paroxysmal events. In depth interview of daily activities of the children, either at home or school, is important for confirming the diagnosis of epilepsy. Particular subjects to be monitored are history of convulsion and starring episodes.
- ADHD is defined by a combination of problems with attention, including poor concentration, distractibility, forgetfulness, frequent careless errors, and incomplete work, and hyperactivity and impulsivity characterized by fidgeting, trouble staying seated, excessive talking, interrupting, and inability to wait or take turns. Symptoms are present in multiple settings including home, school, and extracurricular activities. Diagnosis is best made by reports from the parents with corroboration from schoolteachers.
- With regard to the clinical manifestations, ADHD may contribute additional psychosocial problems either within the family, classroom, or society. Clinicians should have more attention to the patients of ADHD, whether such clinical presentation is as part of epilepsy or not.
- There is a classification of psychosis of epilepsy (POE), established by Kanner. He made 5 categories of POE, e.g., (1) ictal POE (associated with seizure activity, (2) postictal POE (transient psychosis occurring within a week of seizure activity), (3) interictal POE (chronic psychotic symptoms not associated with seizures), (4) alternative psychosis (forced normalization, symptoms following control of seizures), and (5) AED-related psychosis (psychosis as a side effect of AEDs).
- Fortunately, the incidence of interictal psychosis associated with epilepsy is rare in children. This probably due to the variable of seizure duration. A number of studies have suggested that seizures, particularly from the temporal lobes, usually have been present for 10 to 14 years prior to the onset of chronic interictal psychosis. As a result, patients have generally passed beyond childhood before onset of psychosis.
- The psychotic episode typically follows a lucid interval of 24-48 hours and lasts on a average for 4-5 days before spontaneously clearing. AED induced psychotic reactions have occurred with phenytoin, ethosuximide, vigabatrin, zonisamide, topiramate, and possibly lamotrigine and felbamate.
- Although psychotic episode in epileptic patients is rare, particularly in children, the clinicians should be aware of this condition. The awareness is especially related to the possibility of AED induced psychotic reactions.
Association between migraine and epilepsy are bidirectional: migraine with aura is associated with an increased risk for developing epilepsy, while the risk for new-onset migraine is increased in people with a history of epilepsy. The prognosis of epilepsy is worse in the presence of migraine.
Migraine may provide a puzzle to the physician, whether it exists as a single entity or has a bidirectional association to epilepsy. In this regard the physician should present a careful history taking related to migraine and epilepsy.
Mothers of children with intractable epilepsy are generally stressed and experienced more emotional problems. In addition, they are increasingly fatigued. Several correlating factors were identified, mostly related to seizure control, mental and physical handicap. Strategies to manage the problem include proper education, seizure control, participation in regular exercise, social support, and psychological counseling.
Maternal fatigue is a serious implication in the management of epilepsy. This condition may be a risk factor for the unsuccessful therapy, especially in intractable epilepsy, and tend to be a factor for raising despair to the mothers’ patients.
The severity and frequency of seizures may contribute to psychosocial problems. Seizures may affect the temporal lobes or limbic structures, which are crucial areas for emotions and coping, as well as cortical areas, which are necessary for cognitive and physical functioning. Studies have demonstrated that frequency and type of seizure injuries correlate with seizure severity and frequency. Patients often report that complex partial seizures – in which the patient is partially aware of altered emotions, hallucinations, experiential phenomena, or behavior – are especially frightening. Patients with more frequent seizures experience the greatest burdens; their healthcare costs are five times greater than those of patients with well-controlled seizures. Greater seizure severity also has correlated with poorer quality of life in many studies of adolescents and adults. However, even patients with well-controlled seizures report that their condition affects their life in many ways. As seizure frequency increases, patients showed more impaired health-related quality of life, in the areas of physical, emotional, vitality, general health, mental health, and social functioning.
Psychosocial problems in epileptic patients need a comprehensive attention of the physician. Clinicians should be aware that epileptic patients – especially in children – are at increased risk for the development of internalizing and externalizing behavior problems. In addition, clinicians should incorporate family factors in their diagnosis and treatment of psychosocial aspect.
Mortality in epilepsy is assessed by means of particular parameters; the mortality rate, the standardized mortality ratio, and proportional mortality rate. Despite an overall good prognosis for seizure control, epilepsy is a potentially life-threatening condition and is associated with increased mortality. This is consistently shown, both in population-based studies and in studies of more selected populations, such as institutionalized patients and clinic attendees.
Epilepsy carries a significant mortality that, on average, is 2-3 times higher than in the general population. Causes of death in epilepsy consist of unrelated deaths (neoplasm outside the central nervous system, ischemic heart disease, pneumonia, others), related to underlying disease (brain tumor, cerebrovascular disease, cerebral infection, inherited disorders), and epilepsy-related deaths (suicides, treatment-related deaths, idiosyncratic drug reactions, medication adverse effects, seizure–related deaths, status epilepticus, trauma, burns, drowning, asphyxia, aspiration, sudden unexpected death in epilepsy).Whilst studies on this subject are sparse, epilepsy-elated deaths in young adults in the United Kingdom, for example, are 3 times higher than standard age-related mortality rates.
People with epilepsy have a mortality rate (the number of deaths that occur in a defined population divided by the person-years at risk in that population) 2-3 times higher than of general population. This is better expressed as the standardized mortality ratio (SMR), which is the ratio of the observed number of deaths in an epilepsy population to that expected based on the age- and sex-specific mortality rates in a reference population, in a given time.
Mortality directly related to epilepsy accounted for 18 of the 53 deaths in first 2 years after diagnosis, which is equivalent to an incidence rate of 6.8 per 1000 person-years (95% CI 4.1-10). After 2 years 110 of the 351 deaths could be attributed to epilepsy itself, or were epilepsy related, with an incidence rate of 3.1 per 1000 person-years (95% CI 2.5-3.6). The data presented suggest that the increased mortality risk in patients with epilepsy is attributable in part at younger age and early after diagnosis. However, the absolute risk is moderate.
Mortality in childhood epilepsy
Death from epilepsy is uncommon in children without a severe neurological disorder sufficient to cause functional neurological deficit and sudden unexpected death in epilepsy (SUDEP) is rare. However, children with epilepsy have more than five times the risk of dying than the general population in the first 15-20 years after diagnosis.
A prospective community-based cohort of 613 children with newly diagnosed epilepsy demonstrates that the mortality is largely confined to children with severe underlying neurological conditions and encephalopathy. Poor seizure control may contribute to the risk independent of these factors. In the age group studied, few deaths are directly attributable to the occurrence of seizures, and sudden unexplained death associated with epilepsy is rare in children.
A cohort study, conducted by Callenbach et al., indicates no indication that children who have non-symptomatic epilepsy have an increased mortality risk compared with the general population, whereas children who have symptomatic epilepsy have a 20-fold increased mortality risk. These data provide guidance for counseling parents of children who have epilepsy.
We can find different terminology within the word of SUDEP. In some articles, SUDEP is an abbreviation of sudden “unexpected” death in epilepsy. On the other articles we may find SUDEP as sudden “unexplained” death in epilepsy. However, both “unexpected” and “unexplained” have no different meaning. The following paragraphs will use “unexpected” rather than “unexplained”.
Sudden unexpected death (SUD) is defined as “non-traumatic death occurring in an individual within minutes or hours of the onset of the final illness or ictus, the individual having been previously relatively healthy, or suffering from a disease which would not ordinarily be expected to produce immediate or sudden death”. SUDEP – sudden unexpected death in epilepsy – is well recognized if not a well understood cause of death in people with epilepsy. No common risk factor, present in all cases of SUDEP, could be found, suggesting the probability of multiple mechanisms behind SUDEP.
However, tonic-clonic seizures are an important proximate cause of SUDEP. In addition, both cardiac and pulmonary derangement have been postulated as proximate causes too. Patients with uncontrolled seizures are at greatest risk for SUDEP. Patients taking multiple anti-epileptic and having co-existing neurologic disease further increase the risk This information creates a risk profile for SUDEP that may help direct preventable efforts.
Most current studies classify each SUDEP case as definite, probably, or possible based on a set of criteria. Definite SUDEP is defined when the following criteria are met: a) history of epilepsy is provided, b) death or cardiorespiratory compromise is sudden and not caused by status epilepticus, c) death is unexpected (no life-threatening conditions), and d) death remains unexplained after review of all evidence including autopsy. Probable SUDEP is defined by (a), (b), and (c) but data are insufficient because of lack of autopsy, and no alternative explanation for death exists. Possible SUDEP is defined by (a), (b), and (c) but an alternative explanation of death is present. Only definite and probable cases are usually used to study SUDEP rates.
Meanwhile, criteria have been suggested by a variety of investigators to diagnose SUDEP. A reasonable synthesis would yield the following requirements:
- The victim must have had epilepsy, defined as recurrent unprovoked seizures
- Death must have occurred unexpectedly, with no obvious medical cause, while in a reasonable state of health, it the absence of trauma or drowning
- Death must have occurred suddenly when observed
- There may or may not have been evidence of a seizure, but status epilepticus must not have occurred; evidence for a seizure could consist of either a witnessed seizure or clinical evidence such as a bitten tongue or cheek
Relative to the general population, mortality in people with epilepsy has long been known to be elevated. Death in epilepsy may related to the underlying brain disease, seizures in dangerous circumstances, status epilepticus, SUDEP and suicide. All efforts related to the management of epilepsy should be addressed to the quality of life as well as decreasing the risk of death.
Patients with epilepsy have been thought to have a higher risk of illnesses than the general population. The illness – out of the epilepsy itself – then is recognized as co-morbidity. Co-morbid condition may precede, occur simultaneously with, or follow the diagnosis of epilepsy. Such co-morbidity consist of somatic, psychiatric, and psychosocial perspective. In a broader sense, poor health status and lower quality of life in epileptic patients are also thought as co-morbidity. Co-morbidity in epilepsy may result in additive burden to the patients’ health and their family.
Despite an overall good prognosis for seizure control, epilepsy is a potentially life-threatening condition and is associated with increased mortality. People with epilepsy have higher mortality rate than of general population. Causes of death in epilepsy consist of unrelated deaths, related to underlying disease, and epilepsy-related deaths SUDEP is classified as definite, probably, and possible. Criteria for diagnosis of SUDEP have been suggested.