Just as epilepsy is not a solitary disease, mental retardation is not a disease, a syndrome, or a specific medical disorder. In 2002, the American Association on Mental Retardation (1) described a disability originating before age 18 years characterized by significant limitations both in intellectual functioning and adaptive behavior as expressed in conceptual, social, and practical adaptive skills. Five criteria were believed to be essential: (a) the limitation in present functioning must be considered within the context of community environments typical to the individual’s age, peers, and culture; (b) to be valid an assessment must consider cultural and linguistic diversity, as well as differences in communication, sensory, motor, and behavioral factors; (c) within an individual, limitations often coexist with strengths; (d) an important purpose of describing limitations is to develop a profile of needed supports; and (e) with appropriate personalized supports over a sustained period, the life functioning of the person with mental retardation generally will improve. These criteria do not state an intelligence quotient (IQ) measurement as a determining factor, but the 1994 (2) and 2000 (3) editions of the Diagnostic and Statistical Manual of Mental Disorders recognized an IQ of approximately 70 or below and further described mild (IQ 50/55 to 70), moderate (IQ 35/40 to 50/55), severe (IQ 20/25 to 35/40), and profound (IQ less than 20/25) categories. An early classification employed IQ levels for educable (50 to 75), trainable (30 to 50), and severely or profoundly retarded (less than 30). A recent trend simplifies the categories to mild (IQs from 50 to 70) and severe (IQs less than 50) (1,4,5). The abilities of a person with mental retardation depend both on intelligence, as measured by formal testing, and social adaptability, which includes interpersonal and group behaviors (4).

The comorbidities of mental retardation include cerebral palsy, autism, epilepsy, and numerous behavioral diagnoses such as attention deficit hyperactivity disorder and oppositional defiant disorder. These comorbid conditions are determined by specific etiologic diagnoses such as chromosomal disorders, neurocutaneous syndromes, central nervous system (CNS) injury, and inherited metabolic disorders (Table 39.1). The overlay of diagnostic categories and etiologies demonstrate that both epilepsy and mental retardation are symptoms of numerous conditions responsible for CNS dysfunction. Not infrequently, the specific cause remains unknown, although advances in neuroimaging, molecular genetics, and metabolic testing may remedy this lack. The relative risk of mental retardation appears to increase with decreasing socioeconomic status (1,4, 5, 6).

Severe mental retardation is found in approximately 0.3% to 0.4% of the general population, or in 10% of the mentally retarded. The mild form has an estimated
incidence of 20 to 30 cases per 1000 livebirths, or 2% to 3% of the population, and is more frequent in males. Approximately 50% of all persons with cerebral palsy have mental retardation (7). Compared with the general population, children with developmental delay and those with a diagnosis of mental retardation are at an increased risk for epilepsy. The incidence of childhood-onset epilepsy associated with mental retardation and cerebral palsy ranges from 15% to 38% (8). The highest rates of epilepsy are found in children with severe developmental disability and multiple handicaps; coexisting cerebral palsy and mental retardation increase the likelihood of epilepsy twofold, compared with either condition alone (8). In these children, intellectual disability results primarily from the underlying brain disease, not from epilepsy (9); however, continued frequent, repetitive, and uncontrolled seizures may produce additional neuropsychological deficits.

The management of epilepsy in the multihandicapped patient begins with careful evaluation and classification. Treatment, though usually pharmacologic, may be etiologically specific in the presence of metabolic disease, involve surgery when malformations or brain foci can be localized, or use diet or vagus nerve stimulation. Practice guidelines from the American Academy of Neurology have addressed the initial evaluation of the patient with mental retardation or global developmental delay (10). Differential diagnoses to be considered will depend on clinical findings and history (Table 39.1). Some refractory epilepsy syndromes—especially encephalopathic epilepsies such as Lennox-Gastaut syndrome, infantile spasms (West syndrome), and malignant partial epilepsy—are more common in the multihandicapped patient than in the general population. Comorbid epilepsy and mental retardation is characterized by multiple, yet poorly described, seizure types, long-standing epilepsy, frequent polytherapy, increased use of sedating antiepileptic drugs (AEDs), and sometimes frequent changes in therapy. In other patients, therapy has remained unchanged for years, despite uncontrolled
seizures and new drugs and modalities, increasing the risk of status epilepticus and seizure clusters. Although many etiologies of epilepsy and mental retardation are long-standing, the new onset of seizures in a person with mental retardation or other neurologic handicap requires a complete reevaluation, including brain imaging studies, because of the equivalent or heightened risk of stroke, neoplasm, and head trauma compared with the general population. Treatment of these individuals is discussed below.

Cerebral palsy frequently shares an etiology with epilepsy, and the disorders often coexist. The term cerebral palsy is applied to a heterogenous group of nonprogressive or static motor disorders of CNS origin that occur early in life (11). Incidence is about 2.5 cases per 1000 livebirths, higher in twins and triplets (12). Early studies suggested an approximately 28% incidence of epilepsy in persons with cerebral palsy, but more recent epidemiologic studies place the combined incidence at 0.8 cases per 1000 livebirths. Individuals with severe cerebral palsy and those with both mental retardation and cerebral palsy run a high risk of epilepsy (8).

Cerebral palsy can be classified into four clinical types: hemiplegic, diplegic, tetraplegic, and dystonic or athetoid. The hemiplegic form manifests as a motor deficit in the second to third month of life and is usually linked to porencephaly or loss of brain volume in a territory of major cerebral vessels (12). Partial epilepsy is thus frequent in these patients. Spastic diplegia is associated with prematurity; newborns or neonates weighing less than 1500 g are at greatest risk. Underlying periventricular leukomalacia is often seen. The less common tetraplegic cerebral palsy results from global ischemia or widespread brain malformation, and usually involves secondarily generalized epilepsy with multiple seizure types. Dystonic cerebral palsy is often secondary to brain injury at the basal ganglia in the last trimester of gestation; kernicterus or hypoxic ischemic damage is a frequent accompaniment (12).

The diagnostic evaluation of children with cerebral palsy parallels that for mental retardation. Perhaps the most important determination is that the motor deficit is static, nonprogressive, and long-standing. The American Academy of Neurology recommends neuroimaging studies; other testing should depend on findings from history, physical examination, and imaging (13). Worsening cerebral palsy should prompt a complete diagnostic reevaluation. Cerebral palsy and epilepsy associated with hydrocephalus managed with ventricular shunting, worsening epilepsy, motor signs, or deterioration in intellectual ability or behavior mandate reevaluation for shunt malfunction and other complications. Initiation or discontinuation of medications for spasticity, movement disorders, or maladaptive behaviors may significantly affect the frequency of seizures.

The appearance of epilepsy in the population with cerebral palsy can vary significantly. Seizures usually have an earlier onset in individuals with severe cerebral palsy than in those with milder forms. The ability to control seizures is frequently related to the severity of the motor deficit. Fewer children with symptomatic or cryptogenic epilepsy associated with cerebral palsy can eventually discontinue AEDs. In one study (12,14), 30 (54%) of 56 children with a significant neurologic handicap had recurrent seizures on withdrawal of AEDs, compared with an overall recurrence rate of 31%.

Autism is a heterogeneous, pervasive developmental disorder that portends lifelong debility (Table 39.2) (2,15,16). Markedly abnormal or impaired development in social interaction and communication skills, evident in the first 3 years of life, affect language and behavior (15,16). Affected children typically do not demonstrate the normal attachment to and interest in parents, caregivers, and peers and also may show little separation anxiety. Children with autistic spectrum disorders may exhibit echolalia and verbal repetition, along with abnormalities in pitch, intonation, rate, and rhythm, as well as frequent stereotypic self-stimulating movements and a fascination for toys or objects with repetitive motion (17). The more recent identification and inclusion of autism in Rett, fragile X, and Angelman syndromes suggest a higher incidence than previously reported (18,19). Epidemiologic studies indicate rates as high as 6 cases per 1000 children (18), with a 3:1 higher incidence in boys. When cases of Asperger syndrome are included, a ratio as high as 15:1 can be seen (20).

Despite multiple etiologies of autistic spectrum disorder, a specific cause is not identified in up to 90% of patients (17). Underlying diagnoses include phenylketonuria, congenital infections (rubella, cytomegalovirus), tuberous sclerosis, and fragile X and Rett syndromes. Functional abnormalities in cerebellar, cortical, and basal ganglia have been suggested. Electroencephalographic (EEG) abnormalities are present in 27% to 65% of individuals; prolonged recordings commonly demonstrate paroxysmal epileptiform activity (21,22). Correlation of EEG abnormalities and clinical seizures is not absolute, even in patients with apparent language arrest, verbal auditory agnosia, and autistic regression associated with Landau-Kleffner syndrome (23, 24, 25). Whether ongoing seizures contribute to autistic regression remains controversial (26). Approximately 70% to 75% of persons with autism have IQ scores below 70 and thus are classified as mentally retarded; 25% to 35% develop some form of epilepsy, with seizures more likely in individuals with low IQs. Hyperactivity, impulsivity, short attention span, oversensitivity to sound and touch, various preoccupations, and self-stimulatory behaviors are common. Difficulties with
transition, along with obsessions and compulsions, frequently need specific treatments. The diagnostic evaluation of the patient with suspected autism requires detailed history taking and developmental screening, along with observation. The American Academy of Neurology evidence-based guidelines suggest extensive use of checklists for autism in toddlers, screening questionnaires, audiologic testing, and screening for lead exposure. Specific genetic and metabolic tests, and screening for other toxins or infections may be indicated. Electroencephalography may be performed if epilepsy is suspected. Brain imaging studies, although rarely helpful, may be ordered in specific cases. Psychological, developmental, and speech and language assessments, along with educational testing are critical (16).