• Causes and features
• Epilepsy epidemiology
• CP epidemiology
• Epilepsy and CP Epidemiology
• Prognosis
• References

Spastic diplegia is most clearly associated with prematurity. Very low-birth-weight infants (<1500 g birth weight) are at high risk for neurologic disability: 1 in 20 survivors has disabling cerebral palsy.1 The cerebral insult occurs at 26 to 32 weeks of gestation, when the periventricular white matter is especially vulnerable. Periventricular leukomalacia results from ischemia and interrupts the descending corticospinal tracts more from the cortical leg areas than the arm areas. Therefore, many of these children have no cortical lesion, and the rate of epilepsy is relatively low.

If the ischemia has been more severe, then cortical structures may be impaired, but predicting which cortical areas will be most vulnerable is not easy. The epilepsy may be partial, but, if there is global injury, then symptomatic generalized epilepsy may occur.

Interestingly, spastic diplegia sometimes occurs in a term infant. Presumably, this condition is caused by an intrauterine insult at approximately 28 to 32 weeks. Sometimes, a cotwin is known to have died at about this time. It has been suggested that spastic cerebral palsy of unknown etiology in singletons often may be the result of a cotwin death, the so-called vanishing twin syndrome.2

Quadriplegic cerebral palsy

Quadriplegic cerebral palsy has many causes. Sometimes, it is the result of global ischemia, but often it is related to severe global brain malformation. Typically, the cortex is widely involved, and the epilepsies often are of the secondary generalized type.

Dystonic or athetoid cerebral palsy

Dystonic or athetoid cerebral palsy has a variety of causes but usually is believed to result from a brain injury in the last trimester of gestation or the perinatal period. The pathologic process centers on the basal ganglia, and the cortex may be completely spared. Etiologies include kernicterus and hypoxic-ischemic damage. The basal ganglia disorder may be very disabling, especially for tongue and mouth movements, but intelligence may be normal despite severe disability.

Sparing of the cortex means that epilepsy usually is not associated unless the insult has been global and severe. The presence of epilepsy therefore reflects global cortical dysfunction, and symptomatic generalized epilepsies prevail.

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Epilepsy is said to occur when an individual has two or more unprovoked seizures. It appears sometime during life in 1% of the general population. Hauser and Hesdorffer3 estimate that 0.4–0.8% of children will have epilepsy by the age of 11 years. Early studies found that the incidence of childhood epilepsy in industrialized populations was 50 to 100 per 100,000 population.4 More recent studies, however, have found the overall incidence of childhood epilepsy to be 40 per 100,000 children per year.5,6 The incidence of epilepsy is highest in the first year of life (120/100,000) and falls dramatically between 1 and 10 years of age to 40–50 per 100,000. It then drops even further in the teenage years, to 20 per 100,000.

A critical issue when considering epilepsy and cerebral palsy is whether the epilepsy is idiopathic or symptomatic. Idiopathic epilepsy appears suddenly with no underlying cause and frequently involves generalized seizures. It often is characterized by:

• a family history of similar seizures
• normal neurologic and intellectual development at the time of onset
• good response to the appropriate antiepileptic drug (AED)
• spontaneous remission of seizures later in life

In contrast, symptomatic epilepsy may be the result of an acquired insult or an indication of an underlying process, such as abnormal neuronal development and migration in the prenatal period. It also may result from a problem within the developing brain due to intrauterine disease. Symptomatic epilepsy is commonly seen in those with cerebral palsy. Its characteristics often are the opposite of those of idiopathic epilepsy:

• no family history of a seizure disorder
• impairment of neurologic or intellectual abilities
• longer need for medication
• lower spontaneous rate of remission of the epilepsy

The seizures of symptomatic epilepsy often are focal but can be generalized.

In most large studies of people with epilepsy only, 20% of seizures are considered to be symptomatic and the remainder either idiopathic (30%) or cryptogenic (50%; no identifiable underlying etiology, and the epilepsy does not take the form of one of the specific idiopathic syndromes).7

It would seem intuitively obvious that most epilepsy accompanying cerebral palsy would be symptomatic, but no sufficiently large or notable studies of seizure type and linkage with a specific area of motor deficit exist.

Seizure type

Because we expect children with focal motor deficits to experience a focal epilepsy and those with quadriplegia caused by global brain abnormalities to have generalized seizures, we should be able to refer to population-based studies of epilepsy to discern the frequency of seizure type. According to the literature, generalized seizures account for 45% of all seizure types, whereas focal seizures with secondary generalized seizures are present in 55% of cases.5,7 Unfortunately, these studies note the presence of only “neurologic abnormality” rather than the specific type of problem (e.g., cerebral palsy, visual impairment, deafness). Therefore, it is not possible to determine the number of children with epilepsy who also have cerebral palsy (and which cortical area is involved) using population-based studies of epilepsy alone.

Genetic predisposition

The importance of a genetic predisposition to epilepsy in those also having cerebral palsy is impressive. The National Collaborative Perinatal Project demonstrated that the incidence of cerebral palsy in offspring was associated with a maternal history of epilepsy.8

The incidence of nonfebrile seizures in offspring of women with epilepsy but without cerebral palsy was associated with a history of motor deficits in siblings, implying a shared genetic susceptibility to epilepsy and cerebral palsy.

The frequency of epilepsy is elevated in first-degree relatives of children with cerebral palsy, implying that genetic factors play an important part in both of these chronic disabilities. When epilepsy was reported in a first-degree relative of a child with cerebral palsy and mental handicap, Curatolo et al.9 reported that epilepsy was 17 times more frequent in those children than in normal controls. Asku10 described a cohort of children with cerebral palsy and epilepsy in whom 16% of first-degree relatives also had epilepsy, as compared to 8% of first-degree relatives of the normal controls. Others have found similar results.3,11

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

"Cerebral palsy" is a term of convenience applied to a heterogeneous group of nonprogressive motor disorders of central origin covering a wide range of cerebral dysfunctions occurring early in life.12 Often included in the case-finding method is an age of at least 3 years, as the diagnosis of cerebral palsy is occasionally difficult at younger ages.

Incidence

Population-based data delineating the incidence of cerebral palsy are available from numerous large, longitudinal registers.1,13–16 These registers yield incidence figures of approximately 2.5 cases per 1,000 live births (Figure 1).

Incidence of cerebral palsy per 1,000 live births from population-based registers from the United Kingdom, Sweden, and western Australia, 1959-1992. Note that data for the Mersey region of the United Kingdom are for 1967-1989 only; Swedish data are to 1990 only. Rates exclude cerebral palsy due to postneonatal causes.

British registers show higher rates of cerebral palsy than western Australian registers:17,18

The Swedish register reports a comparable rate of 2.5 per 1,000 live births among singletons in 1993.15

Etiology

The etiology of cerebral palsy is thought to be multifactorial and is incompletely understood. Early descriptions indicated that birth injury was responsible, giving rise to a whole generation of pregnancy and delivery interventions. Despite these interventions, the incidence of cerebral palsy has not declined, and recent information indicates that only 2–10% of cases are caused by intrapartum hypoxia.8,19,20 A small additional percentage (perhaps 15%) may be the result of postneonatal difficulties.

Evidence therefore favors a prepartum origin for most cases of cerebral palsy. Poor intrauterine growth is an important risk factor for cerebral palsy in infants with a gestational age greater than 33 weeks.21 Approximately 40% of infants who develop cerebral palsy weigh less than 2,500 g at birth, and one study of spastic cerebral palsy found nearly 50% of these infants to have associated prenatal factors, as compared with about 20% of those infants weighing more than 2,500g.

Overall, however, 50% of cerebral palsy patients were shown not to have experienced any prenatal, perinatal, or neonatal factors.22 Further in-depth studies are needed to elucidate causal pathways to cerebral palsy.

Types

The predominant types of cerebral palsy identified in 756 children within the western Australia registry(1975–1990) 14 were:

• hemiplegia (36%)
• diplegia (32%)
• quadriplegia (16%)
• extrapyramidal (ataxia, hypotonia, and dyskinesia) (16%)

A marked increase in the number of children with quadriplegia and extrapyramidal cerebral palsy has been noted in this register since 1975. This may be due to the increased survival of low-birth-weight and premature infants or, perhaps, better recognition of extrapyramidal cerebral palsy. Other registers have similar information.

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40. With permission from Elsevier (www.elsevier.com).

Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

The population-based study in Goteberg, Sweden by Hagberg et al.15 found that 28% of people with cerebral palsy also had epilepsy. An update of this study published in 2003 reported that 38% (55/146) developed epilepsy by 6 to 14 years of age.40 Similarly, the Danish Cerebral Palsy Register reported that 27.1% of patients born with cerebral palsy between 1979 and 1986 also had epilepsy.16 Data from western Australia from 1975 through 1994 record the incidence rate of epilepsy to be 37% (618 of 1,664).14 The type of seizure associated with each type of cerebral palsy is not described within these registers.

The rate of combined epilepsy and cerebral palsy of 0.8 per 1,000 live births has remained constant over 25 years. With improvements in neonatal care during the last 20 years, the number of surviving premature and low-birth-weight babies has increased, with a concomitant increase in the rate of cerebral palsy.

Severity of cerebral palsy

Children severely affected by cerebral palsy seem to be more likely to develop epilepsy. This aspect was studied in Rochester, Minnesota, between 1950 and 1976, when 64 cases of cerebral palsy were identified.23 Of patients with severe cerebral palsy (defined as function limited to mechanical aids and characterized by marked difficulty) 52% also developed epilepsy. Conversely, epilepsy was present in 23% of those with mild to moderate cerebral palsy. Although the sample is small and spans the years before modern prenatal care, more recent data from western Australia support these findings. Watson and Stanley (personal communication) found that 65% of children with severe cerebral palsy born between 1975 and 1994 developed epilepsy, as compared with 24% of children with minimal, mild, or moderate cases of cerebral palsy.

A history of neonatal seizures is frequently found in children with the dual pathology of both epilepsy and cerebral palsy. Kwong26 found this association in 19% and Carlsson40 found it in 24% (23/55). Most of the children’s seizures were thought to be of prenatal origin.

Type of cerebral palsy

The frequency of occurrence of epilepsy varies according to cerebral palsy type:

Aicardi24 combined data from several studies. Carlsson’s study40 is population-based. Hadjipanaysis et al.25 studied a clinic-based group of 323 children from Greece with cerebral palsy, and found that overall, 41.8% had epilepsy. As shown above, Kwong et al.26 in Hong Kong also found very different epilepsy frequency statistics among 32 children with these dual handicaps, depending on the type of cerebral palsy present.

Referral and diagnostic criteria for all these studies differed, and all had small sample sizes. Therefore, the studies are unlikely to represent the true incidence of epilepsy according to cerebral palsy type. Nonetheless, it is generally believed that patients with quadriplegia and hemiplegia develop epilepsy more often than do those with diplegia. Extrapyramidal cerebral palsy has had the lowest rate of associated epilepsy, probably about 10–15%.

Age at onset

Age at onset of the epilepsy has a close relationship with the type of cerebral palsy:26

Similar results were described from a Greek referral center27 following up 178 children with epilepsy and cerebral palsy: The prevalence of epilepsy in this clinic was 36%, and the onset of seizures occurred in the first year of life in 73% of the children. Carlsson40 in Sweden found that 91% had developed epilepsy by 6 years of age. It appears that earlier age of onset of epilepsy is correlated with an increased severity of cerebral palsy, and the story of whether or not a child with cerebral palsy will develop epilepsy is almost completely written by the age of 6 years.

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised May 2004 by Steven C. Schachter, MD, and Carol Camfield, MD, epilepsy.com Editorial Board.

Berg and Shinnar29 completed a meta-analysis of 25 AED discontinuation studies. The number of years that a patient had to be seizure-free before drug discontinuation was not addressed, but the standard of practice at the time when most studies were conducted required 2 to 5 seizure-free years. Most of the reviewed studies did not specifically indicate a diagnosis of cerebral palsy. Therefore, the authors were able to consider only the effect of a more ill-defined term, motor deficits. In general, the relapse rate for epilepsy patients after 2 years of medication cessation was 30%. For children with “motor deficits” (neurologic abnormality), however, the relative risk of relapse was 1.79 (confidence interval, 1.13–2.83), as compared to those whose epilepsy had an idiopathic cause (i.e., no neurologic or cognitive problems).

In a study of 97 consecutively evaluated children who had been seizure-free for 1 year, regardless of seizure type or cause, AEDs were withdrawn over 4 to 8 weeks.28 Overall, 39% experienced relapse within the next 24 months (mean follow-up, 32 months). For children with a significant neurologic abnormality (one that interfered with activities of daily living), the rate of recurrence was 51%, compared to 32% for those with no neurologic abnormality. Cerebral palsy was not specifically identified in this study, but more than 90% of children who were reported to be “neurologically abnormal” most likely had cerebral palsy.

In the same study, 59% of those with remote symptomatic epilepsy experienced recurrence of seizures, versus 34% of those with idiopathic etiology.

In a cohort of children with epilepsy in Nova Scotia, 383 children became seizure-free while taking AEDs for a long enough period that withdrawal of medication was attempted.30 Of the 293 without neurologic handicap, 90(31%) had recurrent seizures within 2 years. Of the 56 children with significant neurologic handicap, 30 (54%) had recurrent seizures, an appreciably higher proportion. Other studies31–33 have also found neurologic dysfunction to be an adverse risk factor for relapse.

Discontinuation of AEDs in children with epilepsy and cerebral palsy

Overall, children with cerebral palsy and epilepsy take longer than those without this dual handicap to achieve a seizure-free period of 1 to 2 years. The control of epilepsies associated with cerebral palsy is especially difficult when the lesions are large or related to syndromes such as West syndrome (infantile spasms) or Lennox-Gastaut syndrome. The child with cerebral palsy plus epilepsy who does become seizure-free for 1 to 2 years has a good chance of remaining seizure-free when medication is withdrawn, however.28 Seizure freedom will eventually be reached by 40% to 60% of these children.

Early studies, such as that of Roger and Bureau34 in 1982, found that 30% of patients with epilepsy and cerebral palsy entered long-term remission after 5 to 15 years of follow-up, as compared to 70% who had epilepsy only. Eventually, 50% had complete seizure control, with 60% off AEDs.

In another study, the Marseilles group described 97 children with severe cerebral palsy.35 The eventual outcome, good or bad, was known within the first 3 years of life. By 14 years of age, 40% were seizure-free, half without medication.

Asku10 was able to discontinue AEDs in 40% of 174 children who were seizure-free for at least 2 years. Sillanpaa et al.36 followed through 1992 a cohort of 245 children with active epilepsy in 1961–1964. Of those with remote symptomatic epilepsy, 45% were in remission, and 24% had stopped all medication.

Although following somewhat different procedures, other investigators have also found that a significant percentage of children with this dual handicap eventually become seizure-free and can discontinue the use of AEDs. In study by Delgado and colleagues,37 AEDs were discontinued in children with epilepsy and cerebral palsy after 2 seizure-free years. During the next 2 years, 42% of those with spastic cerebral palsy experienced relapses. Those with hemiparesis had the highest relapse rate (62%), whereas those with diplegia had the lowest (14%).

In the study by Zafeiriou et al.,27 AEDs were discontinued after 3 seizure-free years. Only 18 of 134 patients experienced relapse over a follow-up period of 5.8 ± 1.2 years. Of the 18 with recurrence, 11 (61%) had hemiplegic cerebral palsy, 4 (22%) had dystonic cerebral palsy, and 3 (16%) had diplegia. These numbers are surprisingly low and may reflect a small sample or referral bias.

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40.
With permission from Elsevier (www.elsevier.com).

Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

1. Cummings SK, Nelson KB, Grether JK. Cerebral palsy in four northern California counties, births 1983 through 1985. J Pediatr 1993;123:230–237.

2. Pharaoh PO, Cooke RW. A hypothesis for the aetiology of spastic cerebral palsy—the vanishing twin. Dev Med Child Neurol 1997;39:292–296.

3. Hauser WA, Hesdorffer DC. Epilepsy, Frequency, Causes, and Consequences. New York : Demos, 1990;18–21.

4. Hauser WA. The prevalence and incidence of convulsive disorders in childhood. Epilepsia 1994;35[Suppl 2]:S1–6.

5. Camfield CS, Camfield PR, Wirrell E, et al. Incidence of epilepsy in childhood and adolescents: a population based study in Nova Scotia from 1977–1985. Epilepsia 1996;37:19–23.

6. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia 1993;34:453–458.

7. Berg AT, Shinnar S, Levy SR, Testa FM. Newly diagnosed epilepsy in children: presentation at diagnosis. Epilepsia 1999;40:445–452.

8. Nayae RL, Peters EC, Bartholomew M, Landis R. Origins of cerebral palsy. Am J Dis Child 1989;143:1154–1161.

9. Curatolo P, Arpino C, Stazi MA, Medda E. Risk factors for the co-occurrence of partial epilepsy, cerebral palsy and mental retardation. Dev Med Child Neurol 1995;37:776–782.

10. Asku F. Nature and prognosis of seizures in patients with cerebral palsy. Dev Med Child Neurol 1990;32:661–668.

11. Ottman R, Annegers JF, Risch N, et al. Relations of genetic and environmental factors in the etiology of epilepsy. Ann Neurol 1996;39:442–449.

12. Badawi N, Watson L, Petterson B, et al. What constitutes cerebral palsy? Dev Med Child Neurol 1998;40:847–851.

13. Pharaoh PO, Cooke T, Cooke RW, Rosenbloom L. Birthweight specific trends in cerebral palsy. Arch Dis Child 1990;65:602–606.

14. Stanley FJ, Alberman E, Blair E. The cerebral palsies: epidemiology and causal pathways. Clin Dev Med 2000;151:208–211.

15. Hagberg B, Hagberg G, Olow I, von Wendt L. The changing panorama of cerebral palsy in Sweden: VII. Prevalence and origin in the birth year period 1987–90. Acta Paediatr 1996;85:954–960.

16. Topp M, Uldall P, Langhoff-Roos J. Trend in cerebral palsy birth prevalence in eastern Denmark: birth-year period 1970–89. Pediatr Perinatal Epidemiol 1997;11:451–460.

17. Pharaoh PO, Cooke T. Cerebral palsy and multiple births. Arch Dis Child Fetal Neonatal Ed 1996;75:F174–F177.

18. Petterson B, Nelson KB, Watson L, Stanley F. Twins, triplets and cerebral palsy in births in Western Australia in the 1980s. BMJ 1993;307:1239–1243.

19. Stanley FJ, Blair E, Hockey A, et al. Spastic quadriplegia in Western Australia. A genetic epidemiological study: 1. Case population and perinatal risk factors. Dev Med Child Neurol 1993;35:191–120.

20. Nelson KB, Ellenberg JH. Antecedents of cerebral palsy. Multivariate analysis of risk. N Engl J Med 1986;315:81–86.

21. Blair E, Stanley FJ. Intrauterine growth and spastic cerebral palsy: 1. Association with birth weight for gestational age. Am J Obstet Gynecol 1990;162:229–237.

22. Blair E, Stanley F. When can cerebral palsy be prevented? The generation of causal hypotheses by multivariate analysis of a case-control study. Paediatr Perinat Epidemiol 1993;7:272–301.

23. Kudrjveev T, Schoenberg B, Kurland L, Grouver H. Cerebral palsy: survival rates, associated handicaps, and distribution by clinical subtype. Neurology 1985;35:900–903.

24. Aicardi J. Epilepsy in brain-injured children. Dev Med Child Neurol 1990;32:191–202.

25. Hadjipanaysis A, Hadjichristodoulou C, Youroukos S. Epilepsy in patients with cerebral palsy. Dev Med Child Neurol 1997;39:659–663.

26. Kwong KL, Wong SN, Kwan TS. Epilepsy in children with cerebral palsy. Pediatr Neurol 1998;19:31–36.

27. Zafeiriou DI, Kontopoulos EE, Tsikoulas I. Characteristics and prognosis of epilepsy in children with cerebral palsy. J Child Neurol 1999;13:289–294.

28. Dooley JM, Gordon K, Camfield PR, et al. Discontinuation of anticonvulsant therapy in children free of seizures for 1 year. Neurology 1996;46:969–974.

29. Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994;44:601–608.

30. Camfield C, Camfield P, Smith B, et al. Biologic factors as predictors of social outcome of epilepsy in intellectually normal children: a population-based study. J Pediatr 1993;122:869–873.

31. Hollowach-Thurston J, Thurston DL, Hixon BB, Keller A. Prognosis of childhood epilepsy: additional follow- up of 148 children 5–23 years after withdrawal of anti- convulsant therapy. N Engl J Med 1982;306:831–836.

32. Peters ABC, Brouwer OF, Geerts AT, et al. Randomized prospective study of antiepileptic drugs in children with epilepsy. Neurology 1998;50:724–730.

33. Matricardi M, Brinciotti, M, Benedetti P. Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy. Epilepsia 1989;30:582–589.

34. Roger J, Bureau M. Unilateral seizures: hemiconvulsions-hemiplegia syndrome and hemiconvulsions-hemiplegia epilepsy. In F Broughton , H Gastaut (eds), The Neurosciences, Electroencephalography and Clinical Neurophysiology [Suppl 35]. Amsterdam: Elsevier, 1982;211–221.

35. Traverse L, Dravet C, Roger J, et al. Epilepsy in children with severe cerebral palsy: outcome and evolution. Dev Med Child Neurol 1994;36[Suppl 70]:32–33.

36. Sillanpaa M, Jalava M, Olli K, Shinnar A. Long-term prognosis of seizures with onset in childhood. N Engl J Med 1998;338:1715–1722.

37. Delgado MR, Riela AR, Mills J, et al. Discontinuation of antiepileptic drug treatment after two seizure-free years in children with cerebral palsy. Pediatrics 1996;97:192–197.

38. Camfield CS, Breau L, Camfield PR. Impact of pediatric epilepsy on the family: a new scale for clinical and research use. Epilepsia 2001;42:104–112.

39. Humphreys P, Whiting S, Pham B. Hemiparetic cerebral palsy: clinical pattern and imaging in prediction of outcome. Can J Neurol Sci. 2000;27:210-219.

40. Carlsson M, Hagberg G, Olsson I. Clinical and aetiological aspects of epilepsy in children with cerebral palsy. Dev Med Child Neurol. 2003;45:371-376.

Adapted from: Camfield CS, Camfield PR, Watson L. Cerebral palsy in children with epilepsy. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;33–40.
With permission from Elsevier (www.elsevier.com).

Reviewed May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.