1. What is it that distinguishes this group from the wider popula- tion and, in many countr ies, has led to the development of spe- cialist psychiatric and social services? Comorbidity The greater the degree of LD, the more likely there are to be other disabilitie s (including motor and sensory components) and other developmental disabilities, notably au tism and attention de \201 cit disorder. It means that a person with LD is likely to have a complex porridge of psychopathology that may extend to include any of the psychiatric dis orders found in the general population. Limited communication blocks descriptions of intern al, subjective experi- ences and perceptions making it dif \201 cult to diagnose disorders such as schizophrenia or obsessive \200\223compulsive disorder. There is a consequent risk of turning tentative inference and therapeutic trial into \201 rm diagnosis and unjusti \201 ed treatment. 2. How does this affect the diagnosis and management of epilepsy? The nature of learning disability The generic needs of people with LD and the services that developed in response have encouraged us to think of a discrete population. However, altho ugh cognitive ability (assessed by intelligence quo- tient (IQ)) has become the most widely used administrative charac- teristic, other qualities contribute to de \201 ning the grou p, particularly the person \200\231s ability to function and cope with everyday life (meas- ured by scales such as the Vineland Adaptive Behavior Scales) and this will vary with thei r circumstances, personality, and motivation. For example, someone with a mild degree of ge neralized LD may be unable to meet the academic demands of school but thereafter cope well enough with marriage and employment. Of those with LD, about 75 \200\22390 % will have it i n a mild degree (IQ = 55 \200\22370), about 1.1 \200\2231.6 % of the general population, th e exact \201 gure depending on the age and circumstances of the group ( 1 ). A much small er pro- portion, about 0.14 % of the population, will have a severe/profound LD (IQ <35). T heir etiology is known for 70 \200\22390 % of those with severe LD ( 2 ) but for only about 50 % of those with mild LD. Rather than a clear, de \201 ned psychiatric disorder, the result is often disturbed behav ior, ampli \201 ed by anxiety or discomfort, which can become suf \201 ciently intense, f requent, or severe as to threaten the physical safety of the individual or those around. At the least, the restrictive or aversive responses affect the quality of their life. All thi s is summed up in the term \200\230challenging behavior \200\231 ( 3 ). The prevalence of psychiatric disorder relates to LD and, indeed, is less frequent where epilepsy is present ( 4 \200\2236 ) although limited studies and variations in methodology make this hard to te ase out. For example, where there is both LD and epilepsy, the prevalence of a schizophreni form psychosis ranges from 24 % ( 7 ) to only 4.4 % ( 5 ) (as against 6 % in those with epi lepsy but of normal ability). The range may re \202 ect an additional factor however, the level of seizure control rather than simply the presence of epilepsy; psycho- sis being mor e frequent in those who have been seizure free for a period ( 8 ). There is also the sugges tion that, in these circumstances, psychosis might be associated with mild LD and depressio n with severe LD. The group is far from coherent, encompassing not only a wide range of age and ability but a lso a collection of developmental dis- abilities of varied form and intensity, giving great individual varia- tion. In common, though, are problems with communication and dependency as well as atypical emotional and behavioral responses. These may form a characteristic pat tern associated with the underlying cause of the LD as its behavioral phenotype. Communication can be very idiosyncratic with large discrepan- cies between verbal and non-v erbal as well as between receptive and expressive abilities. The patient is likely to have dif \201 culty in reporting any adverse effects from treatment as well as a limited capaci ty to understand its implications. This gives the parent or Prevalence In the community the prevalence of epilepsy in adults with LD is about 16 \200 \22326 % compared with 0.4 \200\2231 % in the general population oxford textbook of epilepsy and epileptic seizures 196 ( 9 \200\22311 ). The risk of epilepsy increases with the degree of LD ( 10 ) and the prese nce of other disorders but the effects of age and genetic syndrome are more variable ( 9 , 12 ). Adults with severe LD are 3 \200\2234 times as likely to have epilepsy as those with mild/moderate LD and, similarly, in childhood, 67 % of those with severe LD have epilepsy c ompared to 7 % of those with mild to moderate LD ( 13 ). The association means that any ove rall \201 gure will depend on the distribution of disability in the population surveyed, let alone those of age, etiology, and accompanying neurological disorders. For example, the presence of cerebral palsy in addition to LD, increases the prevalence 10-fold ( 14 ). \227\206 Prader Willi syndrome : the result of a failure to express (paternal) genes at 15 q11 \200\223q13. Seizures occur in up to a fourth of those with this syndrome and may be as sociated particularly with a deletion genotype (as against uniparental disomy) ( 30 ). \227\206 Angelman syndrome : seizures start in the \201 rst 3 years of life are varied, multiple, and dif \201 cult to control ( 31 , 32 ) \227\206 Autism : \226 Epilepsy can certainly make the symptoms of autism worse. The question became whethe r epilepsy might mimic autism, open- ing the way to therapeutic trials of antiepileptics fo r autistic symptomatology. These were unsuccessful and the present per- ception is that the two disorders may have common causation. Seizures begin before 5 years of age for 65 % of people with an LD and before 20 years for a further 30 % ( 15 ). Thereafter, the preva- lence of epilepsy remains relatively constant and, although increased mortality is related to seizure type and frequency, the cause of d eath seldom relates directly to the seizures ( 16 , 17 ). The epilepsies in LD tend to be r efractory, only a minority becoming seizure free. However, a retrospective study in a speci alist epilepsy center found signi \201 cant improvement over time with, as might be expect ed, the greatest shift in those who started with greatest seizure frequency. This found, in contrast with a Finnish study ( 18 ), 84 % remained seizure free, possibly because of a mo re cautious approach to wean- ing people off their medication (19). One recurrent lesson is that successful treatment, particularly in this population, depends on the clinicians \200 \231 degree of expertise in epilepsy ( 16 , 19 ). \226 A meta-analysis, although hampered by the variable method- ology and limited number of cases, con \201 rmed that the preva- lence of epilepsy in autism was associated with th e degree of LD and was probably more frequent in females ( 9 ). However, even after allowin g for LD, epilepsy is more frequent in autism compared to the general population. \226 Two categories of autism may be discerned; 80 \200\22390 % of people have primary/es sential autism where there is a greater herit- ability with a higher incidence in close rel atives, no signi \201 - cant dysmorphology, and a higher degree of ability. The other grou p, secondary/complex/syndromal autism, comprises 10 \200\22320 % and is associated with und erlying medical disorders, dysmorphology, and lower levels of ability; this group is more l ikely to have epilepsy and, then, a higher seizure frequency. Tonic \200\223clonic seizures are experienced by 60 % , absences by 37 % , and myoclonic je rks by 21 % ; drop attacks and complex partial sei- zures occurred in only 7 % and 6 % resp ectively and nearly half the group had only one type of seizure ( 15 ). In adults, however, there is likely to be a much higher prevalence of complex partial seizures (sometimes with secondary generalization) and a lower occurrence of absence seizures and myoclonic jerks. However, certain disor- ders bring their own characteristic patterns of epilepsy: \226 The prevalence of epilepsy in the essential group ranges from 1.3 % ( 33 ) to 7.4 % ( 34 ) depending on the population studied. There is a sustained debate about the relations hip of autistic regression to the epilepsies although supportive evidence is thin ( 35 , 36 ). \227\206 Tuberous sclerosis : epilepsy, often intractable, occurs in up to 80 \200\22390 % of patients, the relationship being summarized in a report by the Tuberous Sclerosis Study group ( 20 ). \227\206 Other disorders : epilepsy occurs in about 75 % of people with Rett syndrome, 50 % with Lesch \200\223Nyhan syndrome, 30 % with Lowe syndrome, 25 % with Rubenstein \200\223 Taybi syndrome, and is linked to callosal agenesis in Aicardi syndrome ( 37 ). \227\206 Down syndrome : at about 0.067 % of the general population in the UK, this accoun ts for about 10 \200\22315 % of the population with LD. The incidence of epilepsy is increa sed with a clear bimodal distri- bution; early-onset epilepsy occurring in about 10 % and l ate-on- set epilepsy, starting in adulthood, being associated with dementia ( 21 \200\22324 ). Of those with dementia, up to 90 % have seizures, a higher prevalence than in the compa rable non-Down population. Most frequently generalized tonic \200\223clonic seizures, they are accompanied in about 10 % of cases by partial complex and myo- clonic seizures. Occasio nally late-onset progressive myoclonic epilepsy may develop ( 25 ); of interest as the gene for Unverricht \200\223 Lundborg myoclonic epilepsy has been identi \201 ed adjacent to t he critical site for Down syndrome on chromosome 21 ( 26 ). The density of neuro \201 bril lary tangles correlates closely with the pres- ence of seizures and with dementia ( 27 ) an d, although seizures may start in any phase of Alzheimer \200\231s disease, they are a poor prognostic sign, death following within 3 \200\2235 years ( 28 ). Behavioral disturbance Physical discomfort, often the result of an ailment as simple as hay fever, toothache, or tonsillitis, can manifest as an increase in habit- ual symptomatology , irritability, or aggression and should be excluded at the start in the assessment of dist urbed behavior. Poorly controlled epilepsy can amplify symptomatology and there is the temp tation to ascribe every unwanted symptom to it. The relatively high prevalence of epilepsy and aggression leads to the suspicion that the o ne may lead to the other and the use of antiepileptic drugs (AEDs) to treat both. \227\206 Ictal aggression is rare in practice and, when it occurs, is usually a defensive automatism directed re \202 exly at anyone seen as intru- sive or threatening ( 38 ). \227\206 Episodic dyscontrol syndrome (or intermittent explosive disor- der, categorized a s an impulse control disorder, 312.34 in the Diagnostic and Statistical Manual of Mental Di sorders, 4th edi- tion) is quite separate. That the recurrent, brief changes of state might be seen as analogous to the symptoms of a seizure cou- pled with a response to AEDs ( 39 , 40 ) does not mean that this is \227\206 Fragile X syndrome : occurring in 0.5 \200\2234.2 % of those with LD, this is the most frequent cause of inherited LD. Seizures begin in childhood in about 20 % of cases bu t start in adulthood in a small subgroup raising the question as to whether their emergence may be a complication of later life ( 29 ) CHAPTER 17 epilepsy in learning disability 197 dependency and disturbance. On top of this comes epilepsy, often intractable, with its perv asive impact on both physical and psy- chosocial well-being; Kerr et al. ( 44 ) give a usef ul overview of the issues and instruments. epilepsy and, indeed, treatment of associated anxiety and depres- sion may be more fruitful ( 41 ). It is reputed to be more frequent in LD although limited communication blocks the subjective account necessary to disentangle this from other mechanisms producing rage. Management Consensus guidelines have been produced by a working group using an evidence-bas ed, modi \201 ed Delphi process ( 45 ). \227\206 Postictal aggression may be a component of the confusional state of someone emerg ing from a seizure. This twilight state can be overshadowed by the characteristics of LD an d those around may assume a greater awareness than is actually present. Their response to d isturbed behavior, applying restraint, for exam- ple, becomes inappropriate and unwittingly in \202 ammatory. Diagnosis and misdiagnosis Epilepsy is both under- and overdiagnosed. A review of misdiag- nosis identi \201 ed \201 ve categories of events which may be misidenti- \201 ed as e pileptic ( 46 ): \227\206 Interictal aggression and irritability probably are part of a wider range of dysp horia that also includes depression, anxiety, and even euphoria ( 42 ). While this may repr esent a prodromal or postictal state, it may become sustained in chronic epilepsy and, at t his point, should be treated appropriately. Certain antiepilep- tic medications are also kn own anecdotally to cause problem behaviors in people with LD. 1. Behavioral: tics, repetitive stereotypies, habitual smiles or grimaces, staring into spa ce, catatonic freezing, and episodic inattentiveness. 2. Physiological: tics, dyskinetic movements, ataxic falls. 3. Syndromal: \226 Gastro-oesophageal re \202 ux is frequent in people with severe LD, affecting as ma ny as 50 % in severe LD and even more for those on AEDs or with particular syndromes (notab ly Cornelia de Lange) or symptoms such as regurgitation ( 47 ). In early childhood it prese nts as Sandifer syndrome with sud- den distress, abnormal postures or spasms, and eye devia - tion ( 48 ). This is beginning to be recognized in adults though limited communication to gether with a lack of characteristic symptomatology mean that diagnosis depends on a high l evel of suspicion ( 49 ). Services LD implies a degree of lifelong dependency requiring varying levels of special edu cation and support which ranges from supplemen- tary input through to outright full-time sp ecialist care in a residen- tial placement. LD services are geared to habilitation that inc ludes not just teaching, training, and supporting the individual but also their family as t hey come to terms both with their child \200\231s disability and then with the process of i ncreasing autonomy. At some stage, the primary responsibility should shift from family to t he individ- ual, carers, and specialist services; the arrival of epilepsy com- pounds the d isability, making it doubly dif \201 cult for a family to trust others to share the load. \226 Symptoms associated with Rett syndrome include breath holding, hand-wringing, and unresponsiveness. 4. Medication: the effects of AEDs. A well-developed service will be a coordinate network of various agencies and disciplines t hat takes a holistic view of the individual \200\231s problems, promoting their independenc e and ability to take part in decision-making. While encouraging the use of mainstream reso urces, the emphasis shifts towards domiciliary services, taking them to individuals and tho se around them rather than being clinic-centered. It is also focused on long-term work rath er than discrete episodes of care or treatment; factors that can provide a sound basis for the inclusion of an integrated epilepsy service. The frequency and familiarity of epilepsy in LD means that the services should be well adapted to its day-to-day management. 5. Psychological: simulated seizures, (interictal) irritability, sudden aggressive bouts (episodic dyscontrol syndrome). On the other hand, non-convulsive or even partial seizures are particularly prone to pass u nnoticed or misinterpreted, especially if the symptoms are attributed to LD, autism or atte ntion de \201 cit dis- order. An eyewitness account is essential. Ideally this is supported by video, made possible by the growth of mobile phone technology. While epilepsy is a clinical diagnosis, the electroencephalogram (EEG) can be helpful in te asing out the differential diagnosis, par- ticularly in conjunction with video and as prolo nged ambulatory recordings. However, the paroxysmal patterns that frequently accompany auti sm or language disorders are so misleading ( 50 ) as to make it unwise to carry out routine recording; the EEG should be used where there are sound clinical grounds for the diagnosis of epilepsy. Service models have changed with the move from institutional to community care. In some are as the initial assessment and ongo- ing support of epilepsy has passed to neurology in a mo del of shared care that varies with the expertise and resources of different localities. Ho wever, in others, the result has been a detrimental detachment from specialist epilepsy res ources ( 16 , 19 ) that high- light the importance for hospital and community services to e stab- lish a clear, formal protocol for the management of people with LD and epilepsy ( 43 ). Neuroimaging has a particular importance because of the fre- quency of malformation in seve re LD. At the same time anxiety and poor communication make it more likely that sedation (o r even general anesthesia) will be needed and its attendant risks taken into account. The impact of epilepsy on people with learning disability The last 30 years have seen subst antial development in the meas- urement of the quality of life \200\224 the social and eco nomic well- being of people with LD, their families and carers in coping with Treatment The main thrust of treatment must be on helping individuals and their families/ca rers \201 nd the best accommodation to the epilepsy. oxford textbook of epilepsy and epileptic seizures 198 Box 17.1 Special issues in the assessment of people with LD ( 53 ) Box 17.2 Special issues in the management of epilepsy in people with LD ( 53 ) \227\206 Diagnosis can be overshadowed both by the characteristics \227\206 Their epilepsy, (often with multiple seizure types, an earlier onset, and longer established) is more likely to be resistant to treatment. and by the comorbidity of intellectual disability. \227\206 These lead to diagnoses that are: \226 False positives \200\224 episodic behavioral and stereotypical \227\206 Its management can be grouped broadly into antiepileptic medication, neurosurgery , and psychosocial intervention. disturbance mimic seizures. \226 False negatives \200\224 partial, absence and sensory seizures are \227\206 Many people with LD are on psychotropic drugs. These may easily missed. interact with AEDs. \227\206 De \201 nitive diagnosis requires a detailed eye-witness account \200\224 \227\206 AEDs can have adverse cognitive and behavioral effects that, ideally supported by video recording. in LD, are more dif \201 cult to discern. \227\206 An assessment of the person \200\231s communication skills may help \227\206 There should be a comprehensive care plan that includes ther- apeutic options, ri sk assessments, carer education and train- ing, the activities of daily living (bathing, fo od preparation etc.), arrangements for independent living and the manage- ment of emergenci es (prolonged seizures). This care plan should be reviewed regularly but at least annually. their inclusion in decisions about their management. \227\206 A useful EEG may not be attainable. \227\206 Abnormal EEGs are frequent in LD and autism, ranging from an increase in backgrou nd slow activity through to epileptiform discharge; they do not necessarily indicate epilep sy. \227\206 In addition to doctors, the multidisciplinary team (which may include community n urses, school nurses, respite carers, physiotherapists, speech and language therapists, cli nical and educational psychologists, occupational therapists, and social workers) plays an important part in the care of these patients. \227\206 Epilepsy is a clinical diagnosis (neurophysiological \201 ndings are only supportive). \227\206 AEDs \200\224 \200\230start low, go slow \200\231. Start at a dose lower than u sually recommended and titrate the dose up more slowly than rec- ommended in the datasheet until either there is an improve- ment or it is outweighed by adverse effects or a theoreti cal maximum is reached. This means balancing the risk of seizure against restrictions on the person \200\231s auton omy. A checklist speci \201 c to LD has been developed to help specialist epilepsy nurses ( 51 ). There is little evidence as to how LD affects drug ef \201 cacy or adverse effect although there is the suspicion that anomalous or paradoxical responses are more frequent; \200 \230expect the unexpected \200\231 being the rule. Polypharmacy is a recurrent issue the mo re so as, besides AEDs, the individual is often taking other drugs, including psychotropics and medical remedies. Together with the effects of drug interactions, pre-existing cogniti ve impairment and poor communication make it dif \201 cult to judge which drug is having w hat impact on an individual. Consequently, although they do not diminish the need for caref ul clinical assessment, the measurement of drug levels may be of more value than in the gen eral population. LD is no bar to a neurosurgical approach to epilepsy provided the usual re quirements have been met ( 52 ). Some of the speci \201 c issues related to the assessment and management of epilepsy in people with LD that clinicians need to consider are summariz ed in Boxes 17. 1 and 17. 2 ( 53 ). \227\206 If a second AED is introduced, again it should be introduced at a low dose and sl owly increased. When an optimum is reached, the \201 rst AED should be slowly weaned. \227\206 The aim should be to use monopharmacy whenever possible. However, the frequency o f resistant epilepsy means that poly- drugstore is common. increase the likelihood of co-morbid psychopathology? Res Dev Disabil 2011 ; 32 ( 1 ): 353 \200\223 7 . 5. Deb S , Hunter D. Psychopathology of people with mental handicap and epilepsy: II. Psych iatric illness . Br J Psychiatry 1991 ; 159 : 826 \200\223 30 . 6. Espie CA , Watkins J , Curtice L , Espie A , Duncan R , Ryan JA , et al . References Psychopathology in people with epilepsy and intellectual disability; an investigation of po tential explanatory variables . J Neurol , Neurosurg, Psychiatry 2003 ; 74 ( 11 ): 1485 \200\223 92 . 1. Leonard H , Petterson B , Bower C , Sanders R. Prevalence of intellectual disability in Western Australia . Paediatr Perinat Epidemiol 2003 ; 17 ( 1 ): 58 \200\223 67 . 7. Matsuura M , Adachi N , Muramatsu R , Kato M , Onuma T , Okubo Y , et al . Intellectual disability and psychotic disorders of adult epilepsy . Epilepsia 2005 ; 46 : 11 \200\2231 4 . 2. Arvio M , Sillanp M. Prevalence, etiology and comorbidity of severe and profound int ellectual disability in Finland . J Intellect Disabil Res 2003 ; 47 ( 2 ): 108 \200\223 12 . 8. Ring H , Zia A , Lindeman S , Himlok K. Interactions between seizure 3. Royal College of Psychiatrists . Challenging behavior: a uni \201 ed frequency, psychopathology, and severity of intellectual disability in a population with ep ilepsy and a learning disability . Epilepsy Behav 2007 ; 11 ( 1 ): 92 \200\223 7 . approach. Clinical and service guidelines for supporting people with learning disabilities who are at risk of receiving abusive or restrictive practices . Report No.: CR114. London : Royal College of Psychiatrists , 2007 . 9. Amiet C , Gour \201 nkel-An I , Bouzamondo A , Tordjman S , Baulac M , Lechat P , et al . Epilepsy in autism is associated with intellectual disability and gender: Evidence from a meta-analysis . Biol Psychiatry 2008 ; 64 ( 7 ): 577 \200\223 82 . 4. Arshad S , Winterhalder R , Underwood L , Kelesidi K , Chaplin E , Kravariti E , et al . Epilepsy and intellectual disability: Does epilepsy CHAPTER 17 epilepsy in learning disability 199 34. Pavone P , Incorpora G , Fiumara A , Parano E , Tri \201 letti RR , Ruggieri M. Epilep sy is not a prominent feature of primary autism . Neuropediatrics 2004 ; 35 ( 4 ): 207 \200\223 10 . 10. McGrother CW , Bhaumik S , Thorp CF , Hauck A , Branford D , Watson JM. Epilepsy in adults with intellectual disabilities: Prevalence, associations and service implications . Seizure 2006 ; 15 ( 6 ): 376 \200\223 86 . 11. Morgan CL , Baxter H , Kerr MP. Prevalence of epilepsy and associated 35. Deonna T , Roulet-Perez E. Early-onset acquired epileptic aphasia (Landau \200\223Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EE G abnormalities: the continuing debate . Brain Dev 2010 ; 32 ( 9 ): 746 \200\223 52 . health service utilization and mortality among patients with intellectual disability . Am J Ment Retard 2003 ; 108 ( 5 ): 293 \200\223 300 . 12. McDermott S , Moran R , Platt T , Wood H , Isaac T , Dasari S . Prevalence 36. Parmeggiani A , Barcia G , Posar A , Raimondi E , Santucci M , Scaduto MC. Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders . Brain Dev 2010 ; 32 ( 9 ): 783 \200\223 9 . of epilepsy in adults with mental retardation and related disabilities in primary care . Am J Ment Retard 2005 ; 110 ( 1 ): 48 \200\223 56 . 13. Shepherd C , Hosking G. Epilepsy in school children with intellectual impairments in Sh ef \201 eld: the size and nature of the problem and the implications for service provision . J Intellect Disabil Res 1989 ; 33 ( 6 ): 511 \200\2231 4 . 37. Clarke DJ , Deb S . Syndromes causing intellectual disability . In: Gelder MG , Andreas en N , L pez-Ibor Jr JJ , Geddes JR (eds) New Oxford Textbook of Psychiatry , pp. 1838 \200\223 48 . Oxford : Oxford University Press , 2009 . 14. Goulden KJ , Shinnar S , Koller H , Katz M , Richardson SA. Epilepsy in children with m ental retardation: A cohort study . Epilepsia 1991 ; 32 ( 5 ): 690 \200\223 7 . 38. Fessler AJ , Treiman DM. Epilepsy and aggression . Neurology 2009 ; 73 ( 21 ): 1720 \200\223 1 . 39. Ruedrich S , Swales TP , Fossaceca C , Toliver J , Rutkowski A. Effect of 15. Branford D , Bhaumik S , Duncan F. Epilepsy in adults with learning divalproex sodium on aggression and self-injurious behavior in adults with intellectual dis ability: a retrospective review . J Intellect Disabil Res 1999 ; 43 ( 2 ): 105 \200\223 11 . disabilities . Seizure 1998 ; 7 ( 6 ): 473 \200\223 7 . 16. Branford D , Bhaumik S , Duncan F , Collacott RA. A follow-up study of adults with learning disabilities and epilepsy . Seizure 1998 ; 7 ( 6 ): 469 \200\223 72 . 40. Stone JL , McDaniel KD , Hughes JR , Hermann BP. Episodic dyscontrol disorder and parox ysmal EEG abnormalities: successful treatment with carbamazepine . Biol Psychiatry 1986 ; 2 1 ( 2 ): 208 \200\223 12 . 17. Forsgren L , Edvinsson SO , Nystrom L , Blomquist HK. In \202 uence of epilepsy on mortality in mental retardation: an epidemiologic study . Epilepsia 1996 ; 37 ( 10 ): 956 \200\223 63 . 41. van Elst LT , Woermann FG , Lemieux L , Thompson PJ , Trimble MR. Affective aggression in patients with temporal lobe epilepsy: A quantitative MRI study of the amygdala . Brain 2 000 ; 123 ( 2 ): 234 \200\223 43 . 18. Sillanp M. Learning disability: occurrence and long-term consequences in childhood-onset epilepsy . Epilepsy Behav 2004 ; 5 ( 6 ): 937 \200\223 44 . 19. Huber B , Hauser I , Horstmann V , Jokeit G , Liem S , May T , et al . Long- term cours e of epilepsy in a large cohort of intellectually disabled patients . Seizure 2007 ; 16 ( 1 ): 35 \200\223 42 . 42. Blumer D , Montouris G , Davies K. The interictal dysphoric disorder: recognition, path ogenesis, and treatment of the major psychiatric disorder of epilepsy . Epilepsy Behav 2004 ; 5 ( 6 ): 826 \200\223 40 . 20. Holmes GL , Stafstrom CE. Tuberous sclerosis complex and epilepsy: recent developments and future challenges . Epilepsia 2007 ; 48 ( 4 ): 617 \200\223 30 . 43. Ring H , Zia A , Bateman N , Williams E , Lindeman S , Himlok K. How is epilepsy treate d in people with a learning disability? A retrospective observational study of 183 individu als . Seizure 2009 ; 18 ( 4 ): 264 \200\223 8 . 21. Collacott RA. Epilepsy, dementia and adaptive behavior in Down \200\231s syndrome . J Intellect Disabil Res 1993 ; 37 : 153 \200\223 60 . 44. Kerr MP , Turky A , Huber B. The psychosocial impact of epilepsy in adults with an inte llectual disability . Epilepsy Behav 2009 ; 15 ( 2, Suppl 1 ): S26 \200\223 30 . 22. Johannsen P , Christensen JEJ , Goldstein H , Kamp Nielsen V , Mai J. Epilepsy in Down syndrome \200\224 prevalence in three age groups . Seizure 1996 ; 5 ( 2 ) : 121 \200\223 5 . 45. Kerr M ; Guidelines Working Group , Scheepers M , Arvio M , Beavis J , 23. McVicker RW , Shanks OE , McClelland RJ. Prevalence and associated Brandt C , et al . Consensus guidelines into the management of epilepsy in adults with an i ntellectual disability . J Intellect Disabil Res 2009 ; 53 : 687 \200\223 94 . features of epilepsy in adults with Down \200\231s syndrome . Br J Psychiatry 1994 ; 164 ( 4 ): 528 \200\223 32 . 24. Prasher V. Age-speci \201 c prevalence, thyroid dysfunction and depressive symptomatol ogy in adults with Down syndrome and dementia . Int J Geriatr Psychiatry 1995 ; 10 ( 1 ): 2 5 \200\223 31 . 46. Chapman M , Iddon P , Atkinson K , Brodie C , Mitchell D , Parvin G , et al . The misdi agnosis of epilepsy in people with intellectual disabilities: A systematic review . Seizure 2011 ; 20 ( 2 ): 101 \200\223 6 . 47. de Veer AJ , Bos JT , Niezen-de Boer RC , Bohmer CJ , Francke AL. Symptoms of gastroesophageal re \202 ux disease in severely mentally retard ed people: a systematic review . BMC Gastroenterol 2008 ; 8 : 23 . 25. Moller JC , Hamer HM , Oertel WH , Rosenow F. Late-onset myoclonic epilepsy in Down \200\231s syndrome (LOMEDS) . Seizure 2001 ; 10 ( 4 ): 303 \200\223 6 . 26. Stafstrom CE. Epilepsy in Down syndrome: Clinical aspects and possible mechanisms . Am J Ment Retard 1993 ; 98 : 12 \200\223 26 . 27. Raghavan R , Khin-Nu C , Brown AG , Day KA , Tyrer SP , Ince PG , et al . Gender differ ences in the phenotypic expression of Alzheimer \200\231s disease in Down \200\231s syndrom e (trisomy 21) . Neuroreport 1994 ; 5 ( 11 ): 1393 \200\223 6 . 48. Nanayakkara CS , Paton JY. Sandifer syndrome an overlooked diagnosis? Dev Med Child Neurol 1985 ; 27 ( 6 ): 816 \200\2231 9 . 49. Somjit S , Lee Y , Berkovic SF , Harvey AS. Sandifer syndrome 28. Prasher VP , Corbett JA. Onset of seizures as a poor indicator of misdiagnosed as refractory partial seizures in an adult . Epileptic Disord 2004 ; 6 ( 1 ): 49 \200\223 50 . longevity in people with Down syndrome and dementia . Int J Geriatr Psychiatry 1993 ; 8 ( 1 1 ): 923 \200\223 7 . 50. Deonna T , Roulet E. Autistic spectrum disorder: Evaluating a possible contributing or causal role of epilepsy . Epilepsia 2006 ; 47 : 79 \200\223 82 . 51. Cole C , Pointu A , W ellsted DM , Angus-Leppan H . A pilot study of the 29. Hagerman PJ , Stafstrom CE. Origins of epilepsy in fragile X syndrome . Epilepsy Curr 2009 ; 9 ( 4 ): 108 \200\223 12 . 30. Fan Z , Greenwood R , Fisher A , Pendyal S , Powell CM. Characteristics and frequency o f seizure disorder in 56 patients with Prader \200\223Willi syndrome . Am J Med Genet A 200 9 ; 149A ( 7 ): 1581 \200\223 4 . epilepsy risk awareness checklist (ERAC) in people with epilepsy and learning disabilities . Seizure 2010 ; 19 ( 9 ): 592 \200\223 6 . 52. Henriksen O , Bj rnaes H , R ste GK . Epilepsy surgery in mental 31. Dan B. Angelman syndrome: Current understanding and research retardation: the role of surgery . In: Sillanp M , Gram L , Johannessen SI , Tomson T ( eds) Epilepsy and Mental Retardation , pp. 105 \200\223 113 . Philadelphia, PA : Biomedica l Publishing Limited , 1999 . prospects . Epilepsia 2009 ; 50 ( 11 ): 2331 \200\223 9 . 32. Fiumara A , Pittal \203 A , Cocuzza M , Sorge G. Epilepsy in patients with Angelman syndrome . Ital J Pediatr 2010 ; 36 : 31 . 53. Deb S . Epilepsy in people with mental retardation . In: Jacobson JW , Mulick JA (eds) Handbook of Mental Retardation and Developmental Disabilities , pp. 81 \200\223 96 . New Y ork : Kluwer Academic Publishers , 2007 . 33. Miles JH , Takahashi TN , Bagby S , Sahota PK , Vaslow DF , Wang CH , et al . Essential versus complex autism: de \201 nition of fundamental prognostic subtypes . Am J Med Genet A 2005 ; 135 ( 2 ): 171 \200\223 80 . This page intentionally left blank CHAPTER 18 Epilepsy in the Elderly Trevor T.-J. Chong and Wendyl D \200\231Souza Introduction Epilepsy has traditionally been thought of as a disease of the young, primaril y affecting infants, children, and adolescents. Increasingly, however, epilepsy is becoming recognized as a common disorder of the elderly ( 1 ). 1 Within that population, it is the third most common neurological disease, after cerebrovascular disease and the dementias. Ep ilepsy today is therefore more a disease of old age, and our aging population will see it e volve into an increasingly important public health issue. Furthermore, although the phe- no menon of population ageing is evident for high-income coun- tries, the changing global econ omic landscape will also see it become an important consideration for low- and middle-incom e countries (LAMICs). In this chapter, we aim to provide a concise and practical reference to guide the treatment of the elderly patient with epilepsy. Epilepsy in the elderly is associated with a signi \201 cant morbidity and mortality. Old age is a signi \201 cant predictor of seizure recur- rence ( 9 , 10 , 13 ), and patients w ith a \201 rst unprovoked seizure have an overall risk of recurrence beyond 2 years of 25 \200\22352 % ( 14 \200\22317 ). Similar to other age groups, this risk is increased in the presence of an abnormal electroencephalogram (EEG) and/or an identi \201 able epileptogen ic substrate ( 15 ). Status epilepticus becomes more common with age, with a 2- to 10-fold increase in incidence in those older than 60 relative to younger adults ( 18 \200\22320 ). This increase is accompanied by a rise in mortality associated with status epilep- ticus, w ith a rate of 38 % in those over 60 to nearly 50 % in those over 80 ( 21 , 22 ). Overall, t he mortality in elderly patients with epi- lepsy is two to three times greater than that of the general popula- tion ( 23 ), which is likely due to their greater susceptibility to sy stemic illnesses, comorbidities, and the underlying etiology of their epilepsy. Together, t hese \201 ndings underline the importance of optimizing the total care of the elderly pat ient with epilepsy. Epidemiology Any cerebral insult can predispose an individual to developing seizures. It is therefore unsurprising that seizures and epilepsy are so common in the elderly, who have a high incidence of stroke and neurodegenerative disorders. The prevalence of unprovoked sei - zures in those aged over 60 is at least 1 % . This rate rises to 1.5 % in those aged over 75, which is approximately twice that of younger adults ( 2 , 3 ). Predictably, the preval ence is even higher (3 \200\2239 % ) in populations such as nursing home residents, who are more likely to suffer from cerebrovascular disease and dementia ( 4 \200\2236 ). 0 1 ) 0 0 0 1 r e p ( 8 The high prevalence of seizures in the elderly (Fig. 18.1 ) is com- mensurate with the high er incidence of epilepsy in this population. Indeed, the incidence of epilepsy is greatest in those over the age of 65 (Fig. 18.2 ) ( 8 \200\22310 ). Above that age, the incidence co ntinues to rise, with an annual incidence of 85.9 per 100,000 in those aged 65 \200\22369, to more than 135 per 100 000 in those aged older than 80 ( 11 ). This is compared to an ove rall incidence of 80.8 per 100,000 people across all age groups. 6 e c n e a v e r 4P l 2 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 Age (years) 1 In most high-income countries, the de \201 nition of an \200\230elderly \200\231 person is held to be one who has exceeded a chronological age of 65 years. Of course, the situati on is different in low- and middle-income countries and, although the United Nations does n ot have a standard numerical criterion for the \200\230elderly \200\231, it has accepted a cutoff of 60 + years. Fig. 18.1 The prevalence of treated epilepsy across age groups in Tasmania, Australia ( 7 ) Imputed prevalence reported (middle curve) with smoother and 95 % con \201 dence interval s also shown (top and bottom curve). The smoother and 95 % con \201 dence interval was obt ained from a log binomial regression model with age modeled as 1/ \210\232age. oxford textbook of epilepsy and epileptic seizures 202 Table 18.1 Identi \201 able aetiologies of symptomatic seizures in the elderly 300 Kelsey-Seybold HMO, 1988 \200\22394 Sweden, 1992 \200\22394 Rochester, 1985 \200\22394 250 Etiology Symptomatic seizures Structural causes 60 \200\22380 % 0 0 0 0 0 1 r e p e c n e d c n 200 \227\206 Cerebrovascular disease ( 8 , 25 , 29 \200\22333 ) (40 \200\22350 % ) , \227\206 Head trauma ( 8 , 25 , 29 , 34 , 35 ) (4 \200\22317 % ) 150 \227\206 CNS infections ( 8 , 25 , 29 ) (5 \200\22310 % ) Drugs and metabolic disturbances ( 36 \200\22339 ) 10 \200\22340 % i 100 I \227\206 Drugs a , toxins, alcohol (5 \200\22310 % ) \227\206 Metabolic disturbances b (6 \200\22330 % ) 50 a Drugs including: psychotropic agents, theophylline, narcotics, antimicrobials (high-dose penicillins and cephalosporins, imipenem, isoniazid, antimalarials), chemotherapeutic agent s (methotrexate, chlorambucil, cyclosporin), anesthetic agents (ketamine, toxic doses of li gnocaine, disopyramide, bupivacaine), anti-arrhythmics (overdose of vera- pamil, propranolo l), diphenhydramine, baclofen, chlorpromazine 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 Age group b Metabolic insults including: hypo-/hypernatraemia, hypomagnesaemia, hypocalcaemia, hypogl ycaemia/non-ketotic hyperglycaemia, uraemia, hypoxia, hyperthyroidism, por- phyria, dialysi s disequilibrium syndrome. Note that the rate of change of the respective metabolites, rath er than their absolute value, predicts seizures. Fig. 18.2 The incidence of epilepsy across age groups. Reproduced from Annegers, J.F., et a l. The incidence of epilepsy and unprovoked seizures in multiethnic, urban health maintenan ce organizations. Epilepsia 1999; 40( 4 ):502 \200\2236. Etiology Symptomatic seizures An \200\230acute \200\231 symptomatic seizure is one that oc curs shortly after a recent epileptogenic insult (e.g. strokes, metabolic disturbances, dru g withdrawal), in contrast to a \200\230remote \200\231 symptomatic seizure which is one t hat occurs in the days to weeks following such an insult. In practice, the distinction betw een acute and remote symp- tomatic seizures is often blurred, particularly in the elderly. This is due to the inherent imprecision of the circumstances surrounding events, and the va rying de \201 nitions for the acute period, from 48 hours to up to 3 months depending on t he underlying etiology ( 24 ). For example, the period for acute symptomatic seizures sec- ondary to alcohol withdrawal is 48 hours, but that secondary to a head injury is up to 14 d ays. Therefore, a more pragmatic approach is to consider symptomatic seizures in the elderl y in relation to their underlying structural or metabolic causes (Table 18.1 ).