eMedicine Specialties > Neurology > Seizures and Epilepsy

Epilepsy in Adults with Mental Retardation

Author: Norberto Alvarez, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital
Contributor Information and Disclosures

Updated: Jun 19, 2008

Introduction

Background

People with mental retardation do not conform to a homogeneous group. Frequency, characteristics, and prognosis of the epileptic disorder in these individuals are strongly related to the cause of mental retardation. Identification of the cause of mental retardation facilitates understanding of the epileptic disorder. Thus, it makes more sense to discuss epilepsy in individuals with mental retardation in the context of well-defined clinical entities. (See Epilepsy in Children with Mental Retardation where a similar approach has been presented.)

However, some general principles applied to this group of individuals. First, epilepsy is the most common comorbid medical condition in persons with developmental disabilities. Second, approximately 1% of the general population has epilepsy; this rate is similar to the prevalence of mental retardation. However, 26% of children with mental retardation also have epilepsy, 37% of children with epilepsy also have mental retardation, and 50% of people with mental retardation and cerebral palsy have epilepsy. The incidence of epilepsy is related to the severity of the intellectual impairment. The rate is around 20% in persons with mild intellectual impairment and can be as high as 50% in those with severe-to-profound intellectual disability. The epileptic disorders are usually complex, involving more than 1 seizure type and being more difficult to treat than disorders in the general population.

The patient’s prognosis is related to the degree of neurologic involvement. Full seizure control is least frequently achieved in individuals with severe intellectual and motor deficits. Because freedom from seizures might be difficult to achieve in many of these individuals, the success of the antiepileptic therapy should not be measured on the number of seizures alone. Aggressive treatment to achieved full control might result in adverse effects that limit the patient’s quality of life.

The rate of sudden, unexpected death is higher in individuals with mental retardation and epilepsy than in the general population; however, the reason is unclear.

For more information, see Medscape's Epilepsy Resource Center.

Clinical

History

  • Neurocutaneous syndromes -Tuberous sclerosis
    • Tuberous sclerosis complex is an autosomal dominant disorder with a predominance of around 1 case in 6000-10,000 population. Two genes, TSC1 and TSC2, are associated with the complex. In a good number of cases, the tuberous sclerosis is the result of spontaneous genetic mutations.
    • The clinical manifestations are protean, and many systems are involved. Abnormal neurologic disorders include autism, mental retardation, seizures, and behavior disorders.
    • Cortical and subependymal tubers, astrocytomas, neural migration disorders, and hamartomas, among other entities, are frequently seen in persons with tuberous sclerosis.
    • Most of the reported studies refer to mainly children, approximately 80% of whom have some form of epileptic seizures; mental retardation affects 60%.
    • In childhood, infantile spasms (ie, hypsarrhythmia) are the most common presentation. As children age, the epileptic disorder changes and, in some, evolves into Lennox-Gastaut syndrome. In older children and young adults, complex partial seizures are the predominant type.
    • With the exception of typical absences, all types of epileptic seizures have been described in persons with tuberous sclerosis.
    • EEGs are abnormal in most instances, with a variety of epileptiform discharges.
    • Hypsarrhythmia is seen in mostly children (and not in adults) and characterized by generalized spike-and-wave discharges and multifocal discharges (which are focal with temporal-lobe predominant). Tuberous sclerosis is the most frequent cause of infantile spasms.
    • In general, the prognosis in terms of seizure management is poor. The epileptic disorder tends to remain active for many years despite medication.
    • Vigabatrin, a medication not available in United States, have been reported to be effective in the treatment of infantile spasms in children with tuberous sclerosis.
    • Surgery might be an option in selected cases. Because affected individuals usually have many different lesions, determining the active lesion is difficult. However, when it is identified, surgical excision might be effective in achieving a free-seizure state for some patients. A systematic review of the literature regarding postsurgical outcome in patients with tuberous sclerosis showed that selective surgery resulted in seizure freedom in 57% of the patients who had undergone operation and improvement in seizure frequency by greater than 90% in another 18% who had undergone operation.1 These results are encouraging. Patients with tuberous sclerosis and intractable seizures should be considered candidates for surgery.
  • Neurocutaneous syndromes -Sturge-Weber-Dimitri syndrome
    • The brain damage responsible for the seizure disorder is the result of chronic cortical ischemia secondary to venous vascular malformations on the meninges. This angiomatosis is usually on the same side as the facial angiomatosis and rarely on the contralateral or bilateral.
    • Brain damage progresses with time and is associated with hemiparesis in 30% of cases and mental retardation in 50-60%. Hemisensory deficits are most common in adults.
    • In general, mental retardation and epileptic seizures are correlated.
    • Focal motor seizures contralateral to the side of hemangioma, which might or might not be followed by secondary generalization seizures, are the most common type of epileptic seizures.
    • EEG findings are abnormal, with spike and wave discharges coming from affected areas. Poorly organized background and excessive slowing are frequently observed in damaged areas.
    • In many instances, the epileptic disorder remits or is well controlled with antiepileptic drugs (AEDs).
    • When seizures are poorly controlled, surgical removal of atrophic areas of the brain is indicated.
    • Most surgeries are performed in childhood. For many years, adults with mental retardation were not considered candidates for surgery; however, some adults with this syndrome may benefit from surgery.
  • Neurocutaneous syndromes -Neurofibromatosis I
    • Only about 3-5% of patients have associated epileptic seizures.
    • Generally, epilepsy is not a major problem but, given the association with intracranial tumors, these patients require close follow-up when seizures are poorly controlled.
  • Cerebral palsy
    • Epileptic seizures are frequently observed in children and adults with cerebral palsy. The incidence is related to the severity of brain damage; it could be as high as 70% in those with the hemiplegic form and 15-20% in those with the diplegic and dyskinetic forms of cerebral palsy. Cerebral palsy is the most common disorder in which mental retardation is associated with epilepsy.
    • In general, the presence of epileptic seizures is related to the extension of involvement of neocortex and the limbic system.
    • Cumulative risk for epilepsy in young adults (aged 22 y) with mental retardation is reported as 15% or 5.2% in those with no disability, increasing to 38% in those with cerebral palsy. The highest risk of 66% is observed in patients who had a postnatal injury.
    • Epileptic disorders might start at any age; however, in most instances the first epileptic seizures are seen during infancy.
    • Seizure disorders are the consequence of brain abnormalities associated with cerebral palsy; however, genetic factors are also important in the development of epileptic seizures.
    • Whether seizures in early life produce more neuronal damage than seizures later in life is not clear, but clinical studies reveal clearly that early seizures are associated with more cognitive deficiencies.
    • However, exceptionally severe seizures per se are responsible for progressive cognitive deterioration in patients with cerebral palsy. If progression of neurological symptoms is observed, then another etiology should be suspected.
    • Practically every type of epileptic seizure has been described in people with cerebral palsy. Generalized tonic, tonic-clonic, and partial complex seizures with or without secondary generalization are observed most frequently. However, myoclonic seizures and atonic seizures also are seen frequently. Typical absences are the least frequent type of seizure disorder in children with cerebral palsy. Some syndromes, such as Lennox-Gastaut, are particularly frequent in adults with cerebral palsy.
    • Most intractable seizure disorders in adults with mental retardation are associated with cerebral palsy.
  • Malformations of cortical development
    • This group of disorders is characterized by a congenital deficiency in neuronal proliferation, migration, or organization. These disorders are described in the chapter Epilepsy in Children with Mental Retardation.
    • The advent of MRI has facilitated identification of these malformations, and as many as 20-25% of children with intractable epilepsy are believed to have these malformations. Most published articles describe these disorders in children; however, the same conclusions should apply for adults.
    • A retrospective evaluation of MRIs obtained in 303 patients with epileptic seizures, aged 12-41 years, demonstrated that 4.3% had migrational disorders. Among the people with mental retardation, the incidence was 13%.
    • In some cases, the first manifestation of epileptic seizures associated with these malformations occurred in adulthood.
  • Autism
    • Approximately 20-30% of children and adolescents with autism develop some form of epileptic disorder.
    • Seizures are observed frequently in autistic patients with severe mental retardation.
    • In a small group of children with autism and language regression, the regression was associated with development of epilepsy or paroxysmal activity in the EEG.
    • In some cases, the clinical regression improved with steroids or anticonvulsant medication.
    • A prospective study involving 120 individuals with an autism diagnosis, mostly limited to persons with moderate to severe degree of mental retardation (individuals with Asperger syndrome were not included) that were observed for a period of 13-22 years showed that the lifetime occurrence of epilepsy was around 38%. Epilepsy was more often seen in females and in those with a severe degree of mental retardation. The presence of epileptic seizures was associated with poor social functioning, poor employment record, the persistence of the autistic features throughout their whole life, and more dependency for activities of daily living. In most instances, the epileptic disorder started in early life and in one third of individuals, the first seizure was already present before age 2 years. In a few individuals, however, the epileptic disorder started after age 18 years.2
  • Chromosomal disorders
    • Fragile X syndrome, one of the most common chromosomal abnormalities in males with mental retardation, is associated with focal seizures of rolandic type. This is an age-limited process and not seen in adults. Seizures respond well to antiepileptic treatment. Follow-up of patients into adulthood reveals the transformation of partial seizures into generalized seizures.
    • Rett syndrome is the most common condition associated with mental retardation in girls. It is characterized by progressive mental and growth retardation. The infant has normal development until age 6-18 months and then has progressive deterioration in functions with marked regression and loss of skills. A peculiar hand movement, even though not diagnostic, is very characteristic of the disease. Other clinical features include deceleration of the head growth, loss of motor skills, mental retardation, autonomic dysfunction with particular changes in the respiratory patterns, and hyperventilation followed by apneas.
      • This syndrome is well described in children in whom epileptic seizures, in many instances refractory to treatment, are seen (50-90% of cases); in most instances starting in this starts in infancy, as early as in third month of life, and by the age of 10 years, 70-80% of the patients that would have developed seizures already have them. Very few individuals will have the first seizure in adulthood.
      • The seizures are mostly generalized and complex partial. In a small number of individuals, seizures consist of infantile spasms or myoclonic epilepsy.    
      • The risk of seizures is higher in those patients who never walk and in those who present with developmental delay in the first 10 months of life.
      • Less information is available in adults than children because, in some cases, the epileptic disorder improves with age.
      • Cases of seizures that are difficult to control are also reported.
      • Diagnosis of Rett syndrome is possible by sequencing the MECP2 gene on the X chromosome. Sequencing detects 99% of mutations. Some of these mutations (pR294X, pR255X and C terminal mutations) might be associated with lower seizure rate.3
      • Use of this new diagnostic test helps define clinical manifestations of Rett syndrome in women. Many women with mental retardation of unknown etiology might have atypical Rett syndrome.
      • Many epileptic medications have been used in these patients. A recent study suggest that carbamazepine was the most effective drug and it was recommended as first choice. Sulthiame (a drug not approved in the United States) and valproic acid were also effective.
      • Besides improving seizure control, topiramate might also improve the respiratory abnormalities frequently present in this syndrome.
    • Epileptic seizures in adults in their late 40s with Down syndrome are seen as an expression of Alzheimer disease, which occurs with greater frequency in individuals with Down syndrome than in the general population. See Alzheimer Disease in Individuals With Down Syndrome.
      • Generalized tonic-clonic seizures are mostly isolated events. Status epilepticus is sometimes seen, but myoclonus is the most common manifestation.
      • In advanced cases, myoclonic seizures are almost constant. These seizures are difficult to control with medication. External stimulation frequently elicit these seizures.
      • EEG findings are normal at the beginning of the disease; however, as the disease progresses, background activity slows generally. Frontal intermittent delta activity can be seen in many cases. In advanced stages, EEG is poorly organized, with predominance of slow theta and mostly delta activity.
      • Photomyoclonic response develops in many cases.
    • Angelman syndrome, in most instances, is the result of deletions in chromosome band 15q11-13 inherited from the mother (class I). In rare cases, it is due to other chromosomal abnormalities. Examples are paternal uniparental disomy, in which both chromosome bands 15q11-13 are inherited from the father (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV).
      • The observation that the phenotype is similar in all types of Angelman syndrome is interesting; however, the epileptic disorder varies in severity.
      • Patients with class I syndrome have severe, intractable epilepsy (mostly myoclonic seizures and atypical absences), but atonic, generalized extensor tonic, flexor spasms, and secondary generalized tonic-clonic seizures have also been reported.
      • Abnormal movements might be difficult to diagnose as an epileptic event; in many instances, these are not directly correlated with epileptiform activities.
      • Background activity in the EEG tends to be normal in adults; however, paroxysmal activities do persist.
      • Epileptic disorder in adults with Angelman syndrome may be resistant to AEDs.
      • Severity of the epilepsy does not correlate to the particular molecular diagnosis.
      • The severity of the epileptic disorder improved after age 8.5 years.
      • Valproic acid and clonazepam can be effective treatment.

Causes

Differential diagnosis of adults with mental retardation who have epileptic seizures is, in general, no different from the differential diagnosis in individuals without mental retardation. That is, concomitant disorders such as trauma, tumors, and infections should be considered. However, diagnosis of epilepsy in persons with mental retardation presents unique difficulties that are discussed here.

  • Nonepileptic events
    • Probably the most common and unrecognized pitfall in diagnosing the cause of seizures in patients with mental retardation is related to the high incidence of nonepileptic events (pseudoseizures) in this population. Nonepileptic events have been documented in 30-40% of individuals with mental retardation referred for evaluation of epilepsy.
    • Studies performed in adults with mental retardation and epilepsy identified the following as potential sources of diagnostic confusion: nonepileptic myoclonus; movement disorders or tonic reflex posturing, with or without gastroesophageal reflex; sleep disorders (eg, obstructive sleep apnea, restless leg syndrome); and stereotyped behaviors, including self-injurious behavior.
  • Comorbidity with psychiatric disorders
    • Psychiatric disorders are seen in 30-40% of individuals with mental retardation. Some manifestations of psychiatric disorders might be confused with epileptic events. On the other hand, psychiatric disorders, mostly in individuals with a severe and profound degree of mental retardation, might be misdiagnosed as epileptic events.
    • Dual effects of some AEDs, which also are effective in psychiatric disorders, add to the confusion.
    • Psychotropic medications might decrease the threshold for epileptic seizures. Some of the adverse effects of psychotropic medications might resemble seizures (eg, myoclonus). Some of these medications might predispose to postural hypotension and syncopal attacks.
  • Characterization of epileptic seizures
    • Characterization of epileptic seizures and epileptic syndromes in this population is very difficult. Most of the time, patients are not able to describe the epileptic crisis. In most instances, the crisis is observed by persons (teachers, parents) who are not familiar with epileptic disorders; only in exceptional situations does the physician or someone trained in epilepsy see the clinical event.
    • Short-lasting epileptic events, or epileptic seizures manifested mostly by subjective symptoms, are very difficult to diagnose in this population.
    • Frequently, more than a single seizure type is seen in the same person. In patients with intractable seizures, Lennox-Gastaut syndrome is predominant; symptomatic generalized epilepsy and partial epilepsies also are frequent. Partial complex seizures are not infrequent and are probably more frequent than generalized absence seizures.

More on Epilepsy in Adults with Mental Retardation

Overview: Epilepsy in Adults with Mental Retardation
Differential Diagnoses & Workup: Epilepsy in Adults with Mental Retardation
Treatment & Medication: Epilepsy in Adults with Mental Retardation
Follow-up: Epilepsy in Adults with Mental Retardation
Multimedia: Epilepsy in Adults with Mental Retardation
References
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Further Reading

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Keywords

epilepsy, mental retardation, seizures, Angelman syndrome, autism, cerebral palsy, Down syndrome, epileptic seizures, fragile X syndrome, malformations of cortical development, neurofibromatosis I, Rett syndrome, Sturge-Weber-Dimitri syndrome, tuberous sclerosis, neurocutaneous syndromes

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Contributor Information and Disclosures

Author

Norberto Alvarez, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Boston Children's Hospital
Norberto Alvarez, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

Joseph F Hulihan, MD, Vice President, Medical Affairs, Ortho-McNeil Janssen Scientific Affairs, LLC
Joseph F Hulihan, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Headache Society, and American Medical Association
Disclosure: Johnson & Johnson Salary Employment; Johnson & Johnson Stock Employment

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Jose E Cavazos, MD, PhD, Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center; Director of the Epilepsy Center, Audie L Murphy Veterans Affairs Medical Center
Jose E Cavazos, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and Society for Neuroscience
Disclosure: Glaxo-SmithKline Honoraria Speaking and teaching; Ortho-McNeil Neurologics Honoraria Speaking and teaching; UCB Pharma Honoraria Speaking and teaching

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

 
 
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