Epilepsy is defined as at least one epileptic seizure; this in practice means two or more epileptic seizures unprovoked by any immediate identifiable cause during a relatively short period of time. Epileptic seizure is a clinical manifestation presumed to result from an abnormal and excessive discharge of a set of neurones in the
brain. An epileptic syndrome is a cluster of symptoms and signs including type of seizure, mode of seizure recurrence, neurological findings, and neuroradiological or other findings of special investigations, customarily occurring together. An epileptic syndrome can have more than one cause or the cause may remain unknown; consequently outcomes may be different. Pseudoseizure is used to denote epilepsy-like seizures without concomitant EEG changes.
Epilepsy and intellectual disability are symptoms of brain origin. The former is an unstable condition, where during the seizure or ictally the behaviour of a person with epilepsy is abnormal, but between the seizures or interictally there is no affect of epilepsy on his or her behaviour. Intellectual disability is a more or less stable condition. However, the categories of the degrees of intellectual disability are neither absolute nor static, as some children may move up or down between them.
This chapter deals with the diagnosis, manifestations, behavioural disorders, frequency, aetiology, treatment, effects of antiepileptic drugs on behaviour, and prognosis of epilepsy in people with intellectual disability.
Diagnosis and differential diagnosis of epilepsy
The diagnosis of epilepsy is clinical and requires the collection of historical data, physical and mental examination, EEG, and laboratory tests such as determinations of blood glucose and electrolytes.
(1) In babies with epilepsy, attention should be paid to changes of skin colour or cardiac rhythm, sucking and smacking, which all may be epileptic phenomena. In people with intellectual disability it may be difficult or impossible to obtain an accurate clinical history from the patient. The clinician often has to depend on relatives or other professionals involved in the care of the patient. In addition to a description of the seizures, a history of the age at onset of epilepsy and the complete clinical picture of the epileptic syndrome are of value.
General factors that provoke seizures include fever, infection, hypoglycaemia, stress, excessive waking, alcohol withdrawal, hyperventilation, some medications, sudden discontinuation of sedative drugs, and specific activity. Fevers associated with infections such as those of the ears, sinuses, upper respiratory tract, or urinary tract are quite common. If seizures are exacerbated, ensure that any treatable infection is identified. The situation is further confused by the fact that seizures can produce the fever, which, however, resolves within an hour. Withdrawal seizures may be precipitated by a sudden discontinuation of drugs such as benzodiazepines which have an antiepileptic effect, although they may have been prescribed for another reason. Some seizures may be associated with a specific activity, especially if this activity induces excitement or anxiety. Exercise-induced seizures occur regularly in some patients.
Many people with intellectual disability have abnormal behaviour that resembles epileptic seizures but is not epileptic in origin. The diagnostic and other problems caused by non-epileptic seizures or pseudoseizures are well known.
(2) Different dyskinesias, psychogenic attacks, and other non-epileptic episodes may be manifested as pseudoseizures at different ages (
Table 10.5.3.1). Sudden aggression and other epilepsy-like conditions (
Table 10.5.3.2) are in practice the most important reasons for the overdiagnosis of epilepsy, and consequently also for overmedication and subsequent intoxication in patients with intellectual disability. On the other hand, non-convulsive epileptic phenomena and even partial seizures (
Table 10.5.3.3) may be difficult to diagnose in people with intellectual disability. The situation is more complicated when patients with intractable epilepsy have both real epileptic seizures and pseudoseizures, for example psychogenic seizures. In such cases the recognition of psychogenic seizures
(3) (
Table 10.5.3.4) helps to identify appropriate treatment.
(4)Using magnetic resonance imaging (MRI), it is possible to identify structural brain abnormalities, including neoplasms, dysplasia, heterotopia, or diseases in the brainstem and/or posterior fossa. If MRI is not available, CT is recommended.
Prolonged video-EEG monitoring of the patients is of use in selecting candidates for epilepsy surgery or in distinguishing between epileptic and non-epileptic seizures. Basically, this enables any behaviour to be analysed in relation to the EEG changes. If this investigation is not available, portable cassette recording of the EEG may also be of considerable value. The diagnosis of subclinical seizures, including minimal behavioural or cognitive changes in the absence of any obvious clinical seizures, can be demonstrated as lengthened reaction times during EEG discharges in the Romny test.
The brain function of people with epileptic seizures and syndromes can be examined by interictal and ictal single-photon emission CT, positron emission tomography, functional MRI, magnetic resonance spectroscopy, and magnetoencephalography together with simultaneous EEG. Such investigations can help to define the epileptogenic brain lesion and thereby guide management including decisions about epilepsy surgery.
Epilepsy and epileptic syndromes at different ages
The main categories in the classification of seizures and epilepsy are primary generalized seizures, focal seizures, and secondary generalized seizures
(5) (
Table 10.5.3.5). The semiologic seizure classification
(6) seeks to provide common descriptive terms for typical ictal symptoms and for seizure evolution (
Table 10.5.3.6). Epileptic syndromes
(7) are quite frequent in people with intellectual disability ranging from early infancy through childhood to adolescence (
Table 10.5.3.7). As understanding of the pathophysiologic and anatomic substrates of epileptic seizures, syndromes and disorders increases, these classifications may need to be reappraised.
(8,9,10)
Infancy
Infants with
early infantile epileptic encephalopathy or Ohtahara syndrome seem initially neurologically normal, but soon develop increasingly frequent seizures with tonic spasms that resemble infantile spasms and are usually resistant to treatment. Severe progressive intellectual disability becomes evident with age. Many die early and most survivals are handicapped. Some may evolve into the West syndrome and some later into the Lennox–Gastaut syndrome (see below). The EEG shows a ‘burst suppression’ pattern with an almost flat tracing for several seconds, alternating with diffuse, high-amplitude, slow wave-and-spike bursts, poorly modified by sleep–wake stages.
(11) The aetiology of Ohtahara syndrome includes usually congenital or acquired malformations of cortical development and diffuse prenatal encephalopathies, the cause of which remains unknown, so far. A report on a case of Ohtahara syndrome included a metabolic defect with cytochrome oxidase deficiency.
(12)Early myoclonic epileptic encephalopathy is another epileptic syndrome occurring during infancy with a grim prognosis.
(13) The predominant seizure pattern is erratic, paroxysmal, fragmentary myoclonus, often associated with other seizure types. Brain malformations are not so common as in Ohtahara syndrome.
Infantile spasms occur usually at the ages of 4 to 6 months and in 90 per cent of cases during the first year of life. The events resemble the Moro reflex with sudden, brief flexion of neck and trunk, raising both arms forwards or sideways, sometimes with flexion at the elbows, and flexion of legs at the hips. Less often, the legs extend at the hips. At the early stage flexion of the neck may be the only or main feature; this may be followed by more complex and dramatic attacks later on. A cry is often associated with the attack either as part of the attack or occurring afterwards as an expression of disquiet. The spasms are usually symmetric, but may be asymmetric or even unilateral. The EEG is chaotic with slow waves of high voltage intermixed with diffuse or asynchronous spikes in both hemispheres or in the contralateral hemisphere in unilateral cases. This
pattern is called hypsarrhythmia. Infants with unilateral spasms need to be examined using a positron emission tomography scan, as contralateral hypometabolism may be due to cortical dysplasia, a condition which may be treatable by resective epilepsy surgery. Aetiology is usually symptomatic including brain abnormalities due to intrauterine infections such as toxoplasmosis, cytomegalic inclusion disease, or rubella. Other aetiologies are brain malformations due to unknown cause. Infants with Down syndrome or tuberous sclerosis may develop infantile spasms.
West syndrome comprises the triad of infantile spasms, hypsarrhythmia, and intellectual disability.
Progressive degenerative brain diseases and neoplasms are rare causes of infantile spasms. Also neurometabolic disorders such as phenylketonuria, maple syrup urine diseases, non-ketotic or ketotic hyperglycinaemia, and urea cycle defects may lead to infantile spasms.
Severe myoclonic epilepsy in infants includes generalized or unilateral febrile clonic seizures, secondary appearance of myoclonic jerks, and often partial seizures. All the children affected suffer from intellectual disability from the second year of life onwards. Ataxia, signs of upper motor neurone involvement, and interictal myoclonus may appear.
(13)
Early childhood
Myoclonic epilepsy of early childhood shares many features with the
Lennox–Gastaut syndrome.
(13) The latter is a group of epileptic disorders of varied aetiology in childhood. West syndrome often evolves into Lennox–Gastaut syndrome characterized by atypical absences, axial, tonic and sudden myoclonic, atonic, partial, and generalized tonic–clonic seizures, diffuse slow interictal spike waves in the waking EEGs and fast rhythmic bursts (10 Hz) during sleep. A progressive decrease in IQ is often found in children with Lennox–Gastaut syndrome.
Myoclonic–astatic epilepsy or
Doose syndrome resembles Lennox–Gastaut syndrome, but is not so severe.
Later childhood and adolescence
Progressive myoclonus epilepsies have the nosological picture of an evolving syndrome of symptoms including massive and segmental myoclonus, myoclonic or tonic–clonic seizures, partial seizures, cerebellar impairment, and higher neurological dysfunctions.
(13) Unverricht–Lundborg disease is most common in the Finnish and North African population, but occur also elsewhere. The disease progresses only over a limited period and stabilizes thereafter.
(14) The age of onset is around 7 years and the disease starts with myoclonus or nocturnal tonic–clonic seizures. The longest lifespans are more than 60 years. The intelligence level is slightly lowered or even normal. Patients with severe intellectual disability have often had drug intoxication.
(15)
Progressive myoclonus epilepsy with intellectual disability (Northern epilepsy) and Lafora disease are more progressive disorders with different gene defects.
(16) Sialidosis and mitochondrial encephalopathy with ragged red fibres may also show myoclonic seizures. Epilepsy is quite common in girls with Rett syndrome, affecting about 90 per cent of the patients. They may have several seizure types including partial, generalized tonic–clonic, and myoclonic seizures, atypical absences, short flexion or extensor spasms, and drop attacks or various combinations of such seizures.
(17)Of the progressive
partial epilepsies, epilepsia partialis Kojewnikow or Rasmussen syndrome type 2 is especially important because the disease is fatal if untreated. The classical model of the association between frequent epileptiform discharges and permanent loss of function is provided by the Landau–Kleffner syndrome or acquired epileptic aphasia. There is increasing evidence that frequent epileptiform discharges, perhaps particularly overnight in the form of continuous spikes and waves during slow sleep, also called electrical status epilepticus, is associated with permanent intellectual impairment if allowed to continue for long periods.
(18)
Adulthood and old age
The proportion of cerebrovascular disorders, brain tumours, chronic alcoholism, and sequelae of brain injuries is increasing with advancing age in the aetiology of epilepsy. From about 35 years of age onwards partial epilepsies become more common than generalized epilepsies. Patients with intellectual disability may also develop these disorders.
