Epilepsy: A Comprehensive Textbook
2nd Edition
© 2008 Lippincott Williams & Wilkins
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Chapter 263
Cerebral Palsy
John B. P. Stephenson
Introduction
Understanding epilepsy is a necessary part of the management of individuals with cerebral palsy.45 Epilepsy is common in all types of cerebral palsy and, in some varieties, it is the rule.
Definitions
The definitions of epileptic seizures, symptomatic epileptic seizures, and epilepsy are the same as those used in other chapters throughout this book. The definition of cerebral palsy (CP) is a little more difficult, insofar as some variation occurs in the way in which the term is used between different authors and different studies. The most frequent definition of cerebral palsy is “a disorder of posture and movement due to a static lesion of the developing brain.” Most authors include cerebral malformations as examples of static lesions of the brain but, in at least one study, cerebral malformations were excluded.20 Many authors include the aftereffects of acute cerebral insults and injuries in infancy and even in early childhood, whereas others would exclude from the CP definition any condition presumed not to have been present before the age of 4 weeks.20 There is considerable force in the argument for limiting the definition of cerebral palsy in this way, insofar as the prognosis with respect to epilepsy differs between those whose brain lesion is of perinatal or prenatal origin and those children with unequivocally postnatal cerebral insults.
A new definition of cerebral palsy was proposed in 20055: “Cerebral palsy (CP) describes a group of disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, cognition, communication, perception, and/or behavior, and/or by a seizure disorder.” From the point of view of this chapter, it is disappointing to see the term “seizure disorder” employed. This sloppy and ambiguous term deserves to be deleted from scientific discourse.38
Authors have exhibited some variability on the definition of the various subtypes of CP but, on the whole, these differences in classification do not materially affect the understanding of epilepsy in the context of CP. The main divisions in the Edinburgh classification were23: (a) hemiplegia, (b) bilateral hemiplegia, (c) diplegia (which might vary from virtually paraplegic to tetraplegic), (d) ataxic CP (including ataxic diplegia and ataxia), (e) dyskinesia (including dystonia and athetosis), and (f) any other form of CP, including mixed forms. Many authors now include ataxic diplegia within the diplegia categories. Certainly, for the purposes of discussion of epilepsy, dystonic CP should be strongly distinguished from athetoid CP, insofar as the liability to epilepsy may be high in the former and low in the latter type. The group described by the Edinburgh School as bilateral hemiplegia will have severe mental retardation, as discussed in the section Risk Factors for Epilepsy.13
Recent studies31,37 of the etiology of CP (with or without epilepsy) have shown a much higher diagnostic yield than was thought likely in the past. This should make one wary of the CP label without firm foundation.
Problems in Diagnosis of Cerebral Palsy
Many conditions can masquerade as cerebral palsy but turn out to be something else.21,40 Most such conditions are individually rare, but parents do not commonly judge the rarity of a condition as a justification for pediatricians or neurologists to make an incorrect diagnosis. Fortunately for the present issue, cerebral palsy imitators complicated by epilepsy or epileptiform attacks are few. Pelizaeus-Merzbacher disease is one such confusing condition.6 One might argue that this is actually an example of cerebral palsy but, of course, the important point is that it is an X-linked disorder and may recur in a future male child.
Another condition with an unequivocally progressive cerebral pathology is the Aicardi-Goutières syndrome.39 Affected children may behave much like patients with cerebral palsy without regression.39 Confirmation of the diagnosis of Aicardi-Goutières syndrome depends on finding elevated cerebrospinal fluid (CSF) and serum α-interferon in the absence of any congenital viral infection.
Another confusing condition is hyperekplexia47 in which affected neonates may be very stiff and troubled by severe nonepileptic convulsions. When a family history of dominantly inherited startle disease is present, the diagnosis presents no difficulty, but in sporadic cases it can be difficult.
Rare, potentially treatable inborn errors of metabolism leading to cerebral palsy and epilepsy have been described. These include defective serine biosynthesis24 deficiency,4 and GAMT deficiency.28a
New conditions will continue to be recognized, and it behooves the child neurologist to question the diagnosis in every patient with “cerebral palsy.” This is particularly so in so-called ataxic cerebral palsy, which some have suggested should not be called cerebral palsy at all,26 insofar as genetic etiologies abound.
Problems in Epilepsy Diagnosis
Having cerebral palsy is no insurance against exhibiting or suffering from the various nonepileptic attacks that may affect the general population.38 We suspect that children with cerebral palsy are more at risk of having epilepsy misdiagnosed in this way because epilepsy is common in cerebral palsy and so expected to be seen. For example, a young child with spastic diplegia may have what we term reflex anoxic seizures38 after falling over and bumping his head just like anyone else who is similarly genetically predisposed. In addition, patients
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with cerebral palsy may have a predilection for various movements having a superficial resemblance to epileptic seizures. In all these situations, keen clinical judgment must be used. The interictal electroencephalogram (EEG) cannot be relied on to assist in the differential diagnosis. Although it has been attested that spikes or epileptiform discharges are more common in children with cerebral palsy who have epileptic seizures, cerebral palsy individuals who have never had epileptic seizures may not uncommonly show spike discharges also.35 When an individual with cerebral palsy has had one or more previous epileptic seizures, it is even less rational to expect that an EEG examination will help to diagnose a new unexplained paroxysmal event.38 On the other side of the coin, those with startle epilepsy36 may not show spikes at all in the ictal EEG; however, such individuals always have other epileptic seizures without the startle provocation.28
Nonepileptic Paroxysmal Disorders in Sleep
It is particularly important not to mistake nonepileptic paroxysmal phenomena associated with sleep for epileptic seizures. Repetitive sleep starts are serial, sleep-related nonepileptic jerks or spasms that may occur in young neurologically impaired children.16 As these children may also have epilepsy,16 the recognition of these nonepileptic sleep starts is necessary to avoid needless increases in antiepileptic therapy.
Second, because of their cerebral palsy, affected individuals may have obstructive sleep apnea with tonic nonepileptic seizures, easily misdiagnosed as the expected nocturnal epileptic seizures.3
In both these clinical situations polygraphy during sleep may be necessary, recording EEG, electrocardiogram (ECG), respiration, and electromyogram (EMG).3,16
Anoxic-Epileptic Seizures: Epileptic Seizures Induced by Syncope
Epileptic seizures induced by syncopes—what we call anoxic-epileptic seizures—may not be rare in children.22 When this occurs in cerebral palsy, diagnosis may be exceptionally difficult. A recent report describes a boy with Cornelia de Lange syndrome diagnosed as having symptomatic epilepsy until it was realized that his clonic and hemi-clonic epileptic seizures—including status epilepticus—were always triggered by obstructive apnea29 and ceased without the need for antiepileptic medication once recurrent upper airways obstruction was prevented.29
Problems in Combined Cerebral Palsy and Epilepsy Diagnosis
The Special Case of Glucose Transporter Deficiency
It has become apparent that one of the most important etiologies of “cerebral palsy” and epilepsy or “epilepsy” is the genetic disorder of glucose transport now known as GLUT-1 deficiency syndrome or GLUT1DS.46 The importance lies not in the frequency of this disorder but in its potential treatment by ketogenic diet, albeit such treatment is not universally successful.25 Affected individuals mostly—but not always34—have epilepsy, and many have a motor disorder that could be described as cerebral palsy. Presumed nonepileptic movement disorders and other paroxysmal events are also seen.46 Insofar as the ketogenic diet is potentially useful for the treatment of these various phenomena, clinicians should consider this disorder early and make careful simultaneous measurements of fasting blood and CSF glucose when in doubt.46
Risk Factors for Epilepsy
The early studies of Ellenberg and Nelson14 indicated that knowledge of the etiology of epilepsy not associated with cerebral palsy was very limited. A number of later studies have addressed such a question in various ways.
Goulden et al.20 studied a cohort of mentally retarded individuals born in Aberdeen, Scotland, between 1951 and 1955. By 22 years, 15% of these had epilepsy. With their definition of cerebral palsy as “having a presumed prenatal or perinatal onset,” the cumulative risk for epilepsy was 28%, 31%, and 38% at 5, 10, and 22 years of age, respectively. This compared with a much lower risk for individuals with mental retardation and no associated disabilities, and a much higher risk of epilepsy in those with postnatal brain injury (defined as a significant brain insult after 28 days of life which might reasonably account for the child’s later functioning). This particular study included a separate group with cerebral malformations but, in fact, the only malformation determined was described as an occipital meningocele.
A careful Italian study9 focused on the risk factors for the co-occurrence of partial epilepsy, cerebral palsy, and mental retardation. In a studied population of 64 children with these three conditions, neuroimaging identified 32 with cerebral malformations and 32 without but with encephalomalacia, periventricular leukomalacia, or diffuse atrophy. These two groups were compared with a much larger population of normal children. The definitions in this study were as follows:
Partial epilepsy met the International League Against Epilepsy (ILAE) criteria. Such seizures had to have begun in the first 3 years of life. Apparently generalized seizures at onset did not exclude a child if persistent partial motor or complex partial seizures appeared within the first 3 years, but partial seizures in West syndrome or Lennox-Gastaut syndrome excluded a child from this study. Cerebral palsy was defined as “a disorder characterized by abnormal control of movement or posture starting early in life and without any recognized underlying progressive disease.” Mental retardation was defined as an IQ of less than 70.
Significant relative risks were found for both familial factors and for maternal and neonatal factors. Any kind of epilepsy occurred in 0.5% of first-degree relatives of controls, whereas in both the groups with cerebral malformation and without cerebral malformation, the epilepsy risk in first-degree relatives was over 7% (95% confidence interval did not include one). Similarly significant maternal and neonatal factors for both groups (with and without cerebral malformation) were: Maternal diseases in the 2 years before pregnancy (such as diabetes, heart disease, hyperthyroidism, and gynecologic disorders), placental pathology, prematurity with delivery later than 31 weeks’ gestation in those who were small for their gestational age, and neonatal convulsions. An enormously increased risk was found for those born at or before 31 weeks’ gestation, all of these from the group without cerebral malformation. The need for cardiopulmonary resuscitation in the neonatal period, used as a measure of presumed asphyxia, was a high risk factor in the group without cerebral malformation, but not a risk factor in those with cerebral malformation. The findings of this study indicate that a number of genetic and prenatal risk factors interact in the genesis of early partial epilepsy with cerebral palsy and mental retardation.
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Ottman et al.32,33 looked at the etiology of epilepsy from a different perspective. In this study of about 2,000 individuals, all had epilepsy but none had severe mental retardation. Of these, 80% had either idiopathic or cryptogenic epilepsy; 18% had postnatal symptomatic epilepsy, defined as having had a cerebral insult 7 or more days before the first unprovoked seizure. Of interest in the present context was the smallest group with neuro deficits (1%). This group consisted of 28 individuals with cerebral palsy and one with mild intellectual impairment. Although the 95% confidence intervals did not include one because of small numbers, the standard morbidity ratios for epilepsy or for idiopathic or cryptogenic epilepsy was 3 or over in the group with neuro deficits from birth. This was no different from the standard morbidity ratios in the case of those with idiopathic or cryptogenic epilepsy, but different from the situation in postnatal symptomatic epilepsy, where the standardized morbidity ratio was 1.
These studies are consistent with other results such as those of Aicardi1 in demonstrating that, whereas postnatal brain damage is frequently the cause of subsequent epilepsy, similar genetic and prenatal factors underlie both cerebral palsy not of postnatal origin and epilepsy when it coexists.
The relationship of mental retardation is complex. Those with mental retardation are more likely to have epilepsy if they also have cerebral palsy, and those with cerebral palsy are more likely to have epilepsy if they are mentally retarded. To a certain extent, these relationships reflect a common etiology, but by no means is enough known. A simple method of demonstrating the relationship of neurologic deficit severity to IQ has been proposed for individuals with childhood hemiplegia.19
The risk of epilepsy in different subtypes of cerebral palsy also varies. It is highest13 in those with what some call double hemiplegia and some quadriplegia, perhaps not surprisingly. Those with dystonic cerebral palsy who may not be easily distinguishable from those in the former group will also have a high incidence. In those with spastic hemiplegia, the relative incidence is intermediate,42 with the lowest frequency in those with preterm related diplegia or athetoid cerebral palsy.
Clinical Features of the Epilepsy
Considerable difficulties arise in classifying the epilepsies in individuals with cerebral palsy, according to the previous international classification. It might be argued that the epilepsies in cerebral palsy ought to be either partial or localization-related, or secondarily generalized. However, there is no a priori reason why genetic epilepsy, such as the primary generalized epilepsies, or even benign partial epilepsy, such as benign rolandic epilepsy,27 should not occur in those with cerebral palsy, with or without mental retardation. For instance, typical absences with 3 per second spike-and-wave can be seen in children with cerebral palsy,1 and one cannot on clinical and EEG grounds say whether that individual has secondary generalized absences or whether there is coincident primary generalized absence epilepsy. This applies to many of the epilepsies in the context of cerebral palsy. Perhaps the argument is specious insofar as, as indicated earlier in the sections Problems in Combined Cerebral Palsy and Epilepsy and Risk Factors for Epilepsy, a common genetic etiology may exist for the cerebral palsy and the epilepsy.
Certain seizure types, such as infantile or juvenile spasms (otherwise called periodic spasms17), or atonic or startle seizures,36 may be more likely to occur in those with cerebral palsy, but almost any type of epileptic seizure is possible.1,2 It is important to recognize that although normal intellect may be preserved when cerebral palsy and epilepsy are combined (see Case 2) even with startle epilepsy,30 intellectual stagnation or decline may occur (see Case 4).
A study from London44 showed that in children with hemiplegic cerebral palsy and overall intelligence within normal limits, the presence of epileptic seizures in the first 5 years of life was associated with defects of cognition, language, and memory. In this study, when hemiplegia was unaccompanied by early seizures, nonverbal functions were almost exclusively impaired. The authors inferred that language displaced spatial abilities. By contrast, when hemiplegia was accompanied by early seizures, nearly all measures of psychologic function were affected, nonverbal and verbal alike. The presence of seizures seemed to be more important than the presence of EEG discharges. Furthermore, the presence of early seizures was more important than the size of the lateralized lesion on imaging: Children with severe neuroradiologic deficits and no seizures did better on verbal IQ, memory quotient, and third-trial paired associate learning than did those with mild neuroradiologic deficit and early seizures. Case 4 provides a more extreme example with documented regression and loss of skills.
Therapy of the Epilepsy and of the Cerebral Palsy
The principles of medical therapy of the epilepsies complicating cerebral palsy are generally similar to those that pertain in other clinical contexts. Little has been written about the use of corticosteroid, but this is alluded to in a case example below (Case 4). The use of rectal diazepam or buccal midazolam has become widespread in the management of children with cerebral palsy and epilepsy, perhaps in part because of the frequency of long hemiclonic seizures.
The place of epilepsy surgery in cerebral palsy has remained rather small, despite impressive reports on the value of hemispherectomy in refractory epilepsy with complicating hemiplegia (see Chapter 178). Section of the corpus callosum and subpial transection are discussed elsewhere (see Chapters 180 and 182). An impressive recent report from Utrecht has shown that epilepsy surgery in children and adolescents with or without prior spasticity does not harm motor performance.43
Baclofen by intrathecal route has increased in popularity as a treatment for spastic and other forms of cerebral palsy. There has been concern that this use of baclofen—insofar as it is a GABA-B antagonist—might be epileptogenic. However, a recent controlled study concluded that in children with spasticity of cerebral origin intrathecal baclofen does not seem to aggravate or induce epilepsy.7
Prognosis
The prognosis of the neurodevelopmental features, in particular cognitive function and the development of mental retardation, has been discussed earlier in “Risk Factors for Epilepsy.” This section focuses on the prognosis for the epilepsy, with brief mention of mortality.
Prognosis of the Epilepsy
Clinical impression of the intractability and unremitting continuation of epileptic seizures in many children with cerebral palsy is undoubtedly biased by patient referral and differential follow-up of those with good and bad outcomes. In a report11 from Dallas, around 25% (531 of 2,086 children with cerebral palsy actively followed) had epilepsy at the time of writing or previously had epilepsy. Since 1985, only 69 or 13% of these children with cerebral palsy and epilepsy had been seizure free for 2 years or more. These children were studied prospectively
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on antiepileptic drug withdrawal. Electroencephalography was done before the antiepileptic drug discontinuation. In all children, therapy was tapered off by 15% to 20% every 2 weeks. Four were lost to follow-up, but the remaining 65 were followed after antiepileptic drug discontinuation until seizure relapse or until at least 2 years without seizures. In the event, the seizure relapse rate was about 41% (i.e., the remission rate was about 60%). Many factors appeared to have no significant effect on whether remission would or would not take place, although, as the authors point out, nonsignificance means only that we are yet unable to state with a high degree of confidence that the factor does have prognostic value. Paradoxically, there is a higher frequency of relapse in those with normal mental development than in those with mental retardation, but this was likely due to the higher incidence of epilepsy relapse in those with hemiplegic cerebral palsy. In this study spastic hemiparesis was the only factor identified that significantly increased the risk of epilepsy relapse after discontinuation of antiepileptic drug therapy. These hemiplegic individuals were more likely to have normal intelligence than were those having other forms of cerebral palsy.
Thus, the vast majority of children with cerebral palsy do not become seizure free, but of those who do, the majority will be able to discontinue antiepileptic drugs. Children with hemiplegic cerebral palsy seem to be an exception to this rule.
Mortality
Epilepsy significantly increases the mortality rate in those with mental retardation,15 and it has been shown8 that independent predictors of this increased mortality are: The type of cerebral palsy (spastic quadriplegia and double hemiplegia having the worst prognosis); the presence of epilepsy (of any type); and the presence of severe or profound mental retardation. In remote symptomatic epilepsy as a whole mortality is increased,10 seizure severity seemingly a factor.41 By contrast, the prognosis for survival in those with hemiplegic cerebral palsy and epilepsy but without mental retardation is excellent (96% at 30 years).8
Case Examples
For those who appreciate the value of detailed clinical observations on individual children, four case studies are provided in this section. One child represents a condition that successfully masquerades as cerebral palsy but has different implications. The other three case studies are of three children with congenital left spastic hemiplegia, with different trajectories and outcomes. These clinical studies may suggest to others further ways of refining the excellent type of epidemiologic studies referred to earlier.
Case 1: Progressive “Cerebral Palsy”
A girl was born at term in 1991 to unrelated parents who had two previous normal children. She presented at age 10 weeks because she was not holding up her head and did not smile. Her left limbs jerked repetitively as she fell asleep. Her development was very slow, but her parents and medical attendants did not observe loss of skills. She smiled once at 3 months and then more so at 9 months, smiling very readily at age 3 years. Initial hypotonia changed to spastic tetraplegia from her second year of life. Seizures consisting of extension of her limbs with quivering for about a minute occurred daily in infancy, at which time the EEG was normal, but diminished to once a week at age 3 years, EEG then showing a considerable quantity of slow spike-and-wave activity. Chilblains (pernio) were prominent, particularly on her toes. The only clinical evidence of a progressive disorder was failure of head growth. Initially, head circumference was on the mean, albeit 2 cm below that expected from her parental and sibling head circumferences, but after age 4 months, growth further declined; by 4 years of age, head circumference was 4 standard deviations below the mean.
Computed tomography head scans demonstrated progressive encephalopathy with periventricular calcifications, later also in basal ganglia and dentate locations, associated with white matter hypointensity. Cerebrospinal fluid contained 40 lymphocytes/mm3. There was no evidence of viral infection, and the huge level of cerebrospinal fluid α-interferon confirmed the diagnosis of autosomal recessive Aicardi-Goutières syndrome.35a,39
Comment
Epilepsy, yes; cerebral palsy, no!
Case 2: Hemiplegic Cerebral Palsy, West Syndrome, and Good Outcome
A first-born male did not show signs of asphyxia after a long labor but was very jumpy at noise at the age of 2 hours and from age 2 days had a tendency to tenseness of his left limbs, with his fontanel bulging when he was upset. Thereafter, his behavior and development seemed normal except that there was a tendency for his left hand to be fisted.
When he presented at the age of 7.5 months, his parents said that about a month previously he had lost his happy disposition and had become lethargic, docile, and unsmiling. At about the same time, he had begun to have runs of spasms five or so times a day, with ten or more spasms in each run about 10 seconds apart. On admission to the hospital, runs of spasms were observed, sometimes with a degree of asymmetry. His head circumference was on the second percentile, and his skull transilluminated excessively on the right. He had a left hemianopia and absent optokinetic nystagmus when the drum or tape was moved to his right. His left hand did not have full voluntary control, only briefly retaining an object. Brain imaging was not done at that time, but years later showed infarction in the right middle cerebral territory. Electroencephalography showed hypsarrhythmia without convincing asymmetry.
He was treated with adrenocorticotropic hormone (ACTH) gel, 40 units daily for 2 weeks, and nitrazepam 1 mg twice daily. He had no further infantile spasms after the first dose of ACTH, and 3 days later he was smiling and taking an interest in his toys again. Repeat EEG after 2 weeks showed no discharges but reduced rhythmic activity over the right.
He received nitrazepam in the same dose until the age of 2 years. He developed intellectually, having a verbal comprehension at the age of 1.5 years of more than 2 standard deviations above the mean. He had left spastic hemiparesis and required lengthening of his Achilles tendon at the age of 3 years. An additional medical complication was an atrial septal defect, which was closed without use of blood at the age of 9 years.
From the age of 4 years, he had occasional episodes of altered consciousness, sometimes with some motor disturbance on the left. These tended to be preceded by a “funny feeling in his tummy”; instances of “sick tummy” were more frequent. Antiepileptic therapy for these simple and complex partial seizures was not required until the age of 11 years, when carbamazepine was introduced. At the age of 12 years, he replied to a letter sent to his parents inquiring about him: “Thank you
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for the letter of interest. My Mum and Dad thought that it would be appropriate for me to write because I am the person you are so considerate of…” At about age 15 years, he began to have startle-induced alterations in the tone of his left limbs, lasting 15 to 30 seconds, the startle stimulus being solely an accidental scuffing of the toe of his left foot on the ground. He was improved by an increase of carbamazepine dose in the sustained release form. At the age of 17 years, he had two episodes of left limb stiffness without startle, but since the addition of vigabatrin, 500 mg daily, he has remained seizure free.
When he was aged 17 years, he discovered that he would have difficulty obtaining a driving license because of his left hemianopia. However, the combination of a life-long habit of frequently shifting his gaze to the left and training in blind sight in his left visual field has enabled him to drive commercially and to achieve complete independence.
When in his 20s, he suffered several attacks of loss of consciousness, preceded by a funny feeling in his abdomen. These were misdiagnosed as a return of his epilepsy, and an EEG was inappropriately requested. In fact, his mother had a long history of vasovagal syncopes with an identical abdominal aura.38
Comment
Aside from illustrating determined human qualities, this case illustrates that neither symptomatic West syndrome nor epilepsy complicating hemiplegic cerebral palsy are bars to intellectual achievement and success in life.18
It is also a powerful reminder that individuals who have had epilepsy may have syncopes as well.
Case 3: Congenital Hemiplegia with Secondary Generalized Myoclonic Epilepsy
This boy’s mother sustained a motor vehicle accident in pregnancy at 22 weeks’ gestation, after which she was unconscious for 2 hours and required an infusion to maintain her blood pressure. He was born normally at term, but a left hemiparesis became apparent later in the first year of life. His development appeared to be otherwise normal.
At age 3.5 years, he first had simultaneous head nods with right arm jerk. Soon after, he had one clonic epileptic seizure from sleep. At age 4 years, jerks became very frequent daily. They appeared to involve head nodding and abrupt dropping of the right upper limb, suggesting negative myoclonus (although surface EMG polygraphy was not undertaken). Interictal EEG showed very frequent runs of high-voltage 2/sec spike-and-wave; this slow spike-and-wave was generalized but of even higher voltage on the right. Computed tomography brain scan showed a smaller right cerebral hemisphere with abnormal gyration and a deep cleft consistent with polymicrogyria. His attentiveness varied with the frequency of his seizures but intellectual assessment showed normal intelligence.
Carbamazepine was associated with worsening of his seizures, and sodium valproate with or without lamotrigine had no consistent beneficial effect. A 2-week course of betamethasone led to marked reduction in seizures and an increase in attentiveness; he went into normal school and has continued on lamotrigine monotherapy with only occasional jerks.
Comment
An example of prenatal origin hemiplegic cerebral palsy with intelligence in the normal range despite severe secondary generalized epilepsy, probably negative myoclonic.7a Selective learning difficulties were expected to become more apparent in school years.
Case 4: Congenital Hemiplegia with Epileptic Encephalopathy
After an uneventful pregnancy, this girl was born at term by emergency cesarean section because of a maternal straight sacrum. There was said to be fetal distress with meconium staining and type 2 dips in labor. The APGAR score was 3 at 1 minute, and she was intubated at 3 minutes for 2 minutes. However, she was well as a neonate except that when about 1 week old, it was noted that whenever she fought out of her shawl or cot covers, it was always with the right hand. Thereafter, although she developed evidence of a left spastic hemiparesis (shown later to be due to a large right middle cerebral infarct), her general development was distinctly advanced, and she spoke many meaningful words, including “what’s that?” before the age of 1 year.
Just after the age of 2.5 years, she had an episode of staring with left hand twitching. At the age of 3.5 years, she had a bilateral clonic seizure of at least 25 minutes’ duration. At the age of 4 years, she began to have blanks, which increased in frequency and began to be described as periods of confusion. EEG from before the age of 4 years showed runs of generalized spike-and-wave discharges, which were nearer to 2 per second but were often at 2.5 to 3 per second with blinking and probable absence. By the age of 5 years, there was also bifrontal slow activity. She received sodium valproate in a dose of 400 mg daily from 4 years 4 months, and 800 mg daily from 4 years 8 months, changing to ethosuximide 500 mg daily, 2 months later.
Cognitive and behavioral decline was noticed by her mother from about the age of 4 years 4 months. Although there was some fluctuation, the girl would no longer sit down and draw people and faces if requested but would run about most of the time. Professional evaluation confirmed the decline. At the age of 4 years 2 months, her expressive language was well above average, and her verbal comprehension not less than 4 years 9 months (the ceiling had not been reached in the tests). By 4 years 11 months, both expressive language and verbal comprehension had dropped to 2 years 6 months. She had also become disorientated and declined in nonverbal skills, and had various behavioral abnormalities.
Short courses of betamethasone initially reduced spike-and-wave activity on EEG and were associated with improved cognition and behavior such that, for example, her Stanford-Binet intelligence was raised from 2 years 11 months at 5 years 2 months up to 3 years 11 months at 5 years 5 months, but such improvements became less and of shorter duration after each successive betamethasone course. In due course, although the atypical absences were eliminated by the betamethasone, her cognition and behavior did not much improve. Over the next 5 years, these atypical absences fluctuated and were often not observed. Very occasional night seizures, possibly tonic–clonic, were reported, but there have been no further seizures of any type observed since the age of 10 years on ethosuximide monotherapy. At the age of 15 years, she has just begun to read but has no road sense, is too friendly with strangers, and has other behavioral difficulties.
Comment
In this previously very intelligent girl with hemiplegic cerebral palsy, severe cognitive and behavioral decline was associated
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with rather subtle epileptic manifestations. Although cortico-steroid administration at first led to improvement, this was temporary, and she is now not likely to be able to live independently, despite remission of her epilepsy. Whether more modern medical or surgical antiepileptic approaches might have prevented this dismal prognosis remains speculative. A good discussion of cognitive and behavioral disturbances as epileptic manifestations is to be found elsewhere.12
Summary and Conclusions
It is essential to make sure that the diagnosis of cerebral palsy is correct and that the diagnosis of the epilepsy is correct. In the case of cerebral palsy diagnosis, both genetic disorders with high recurrence risk and rare treatable cerebral disorders should be excluded. In the case of the epilepsy diagnosis, special attention should be paid to nonepileptic events in patients with cerebral palsy that masquerade as epileptic seizures. Even epileptic seizures do not always imply epilepsy, as the section on anoxic-epileptic seizures has illustrated. Obviously, antiepileptic therapy should be avoided when it is not appropriate.
It appears that cerebral palsy and epilepsy are linked both by etiology and prognosis. The outlook is not universally bad, but we have little evidence on which to make improvements. Especially terrible are regressions in mental capacity linked in some way to the epileptic component of the cerebral palsy.
References
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7a. Caraballo R, Cersosimo R, Fejerman N. A particular type of epilepsy in children with congenital hemiparesis associated with unilateral polymicrogria. Epilepsia. 1999;40:865–871.
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