5 . Palmini A , Najm I , Avanzini G , Babb T , Guerrini R , Foldvary-Schaefer N , et al. Terminology and classi \201 cation of the cortical dysplasias . Neurology 2004 ; 62 : S2 \200\223 8 . 6 . Blumcke I , Vinters HV , Armstrong D , Aronica E , Thom M , Sprea \201 co R . Malforma tions of cortical development and epilepsies . Epileptic Disord 2009 ; 11 : 181 \200\223 9 3 . 7 . Chamberlain WA , Cohen ML , KA Gyure , Kleinschmidt-DeMasters BK , Perry A , Powell SZ , et al. Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development) . Epilepsia 2009 ; 50 : 2593 \200\223 8 . The hippocampus serves a major role in all aspects of conscious, declarative memory, i.e. s emantic memory for facts and concepts, episodic memory, and spatial memory ( 88 ). Notwiths tanding, bilateral damage of both hippocampi induces profound antero- grade amnesia in huma ns. ( 89 ). Neuropsychological lesion studies, functional imaging in humans, as well as exp erimental animal models linked memory function particularly with the dentate gyrus ( 90 ). Thus, standardized cognitive evaluation programs in epi- lepsy patients submitted to surgic al treatment offer the unique opportunity to study such higher brain function in humans. Ev idence has already been achieved pointing to the impact of den- tate granule cell neurogene sis on learning and behavior in rodents ( 91 , 92 ). We have studied this issue in human hi ppocampus obtained from epilepsy surgery. Comparing memory performance (tested by amobarbit al anesthesia (Wada test) in patients subse- quently submitted to surgical resection of eit her the left or right hippocampus) with the extent of hippocampal cell loss within the inte rnal limb identi \201 ed granule cell density as most signi \201 cant predictor accountin g for 78 % of the total memory capacity in an individual patient ( 57 ). It \200\230sugges tively \200\231 points to neurogenesis as neurobiological substrate of memory acquisition ( rather than sei- zure etiology) and that a run-down of the neurogenic propensity in chronic seizure disorders compromises higher cognitive brain function. Indeed, we experimentally c on \201 rmed this hypothesis when isolating, proliferating, and differentiating adult huma n stem cells from the dentate gyrus of TLE patients with HS ( 58 ). There was a highly sign i \201 cant correlation between the proliferation and 8 . Blumcke I , Sprea \201 co R. An international consensus classi \201 cation for focal cortical dysplasias . Lancet Neurol 2011 ; 10 : 26 \200\223 7 . 9 . Bl mcke I , Thom M , Aronica E , Armstrong DD , Vinters HV , Palmini A , et al. The cl inico-pathological spectrum of Focal Cortical Dysplasias: a consensus classi \201 cation p roposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission . Epilepsia 2011 ; 52 : 158 \200\223 74 . 10 . 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Hippocampal neuron loss in temporal lobe epilepsy: correlation w ith early childhood convulsions . Ann Neurol 1987 ; 22 : 334 \200\223 40 . hippocampal formation of kainic acid-treated rats . J Neurosci 1985 ; 5 : 1016 \200\223 22 . 64 . Altman J, Bayer SA. Migration and distribution of two populations of 82 . Sutula T , Cascino G , Cavazos J , Parada I , Ramirez L . Mossy \201 ber synaptic re organization in the epileptic human temporal lobe . Ann Neurol 1989 ; 26 : 321 \200\223 30 . hippocampal granule cell precursors during the perinatal and postnatal periods . J Comp Neu rol 1990 ; 301 : 365 \200\223 81 . 65 . Eriksson PS , Per \201 lieva E , Bjork-Eriksson T , Alborn AM , Nordborg C , 83 . Parent JM , Tada E , Fike JR , Lowenstein DH . Inhibition of dentate granule cell neur ogenesis with brain irradiation does not prevent seizure-induced mossy \201 ber synaptic reorganization in the rat . J Neurosci 1999 ; 19 : 4508 \200\223 19 . Peterson DA , et al. 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Reelin is a positional signal for the lami nation of dentate granule cells . Development 2004 ; 131 : 5117 \200\223 25 . 88 . Squire LR , Stark CE , Clark RE . The Medial Temporal Lobe . Annu Rev Neurosci 2004 ; 27 : 279 \200\223 306 . 72 . Ge S , Goh EL , Sailor KA , Kitabatake Y , Ming GL , Song H . GABA 89 . Scoville WB , Milner B. Loss of recent memory after bilateral regulates synaptic integration of newly generated neurons in the adult brain . Nature 2006 ; 439 : 589 \200\223 93 . hippocampal lesions . J Neurol Neurosurg Psychiatry 1957 ; 20 : 11 \200\223 21 . 90 . Kesn er RP , Lee I , Gilbert P. A behavioral assessment of hippocampal function based on a subre gional analysis . Rev Neurosci 2004 ; 15 : 333 \200\223 51 . 73 . Ramirez-Amaya V , Marrone DF , Gage FH , Worley PF , Barnes CA . Integration of new ne urons into functional neural networks . J Neurosci 2006 ; 26 : 12237 \200\223 41 . 91 . Leuner B , Mendolia-Loffredo S , Kozorovitskiy Y , Samburg D , Gould E , Shors TJ . Le arning enhances the survival of new neurons beyond the time when the hippocampus is require d for memory . J Neurosci 2004 ; 24 : 7477 \200\223 81 . 74 . van Praag H , Schinder AF , Christie BR , Toni N , Palmer TD , Gage FH . Functional ne urogenesis in the adult hippocampus . Nature 2002 ; 415 : 1030 \200\223 4 . 75 . Hastings NB, Gould E. Rapid extension of axons into the CA3 region by adult-generated granule cells . J Comp Neurol 1999 ; 413 : 146 \200\223 54 . 76 . Zhao S , Chai X , Bock H H , Brunne B , Forster E , Frotscher M. Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for Reelin and Disabled 1 . J Comp Neurol 2006 ; 495 : 1 \200\223 9 . 92 . Shors TJ , Miesegaes G , Beylin A , Zhao M , Rydel T , Gould E . Neurogenesis in the adult is involved in the formation of trace memories . Nature 2001 ; 41 0 : 372 \200\223 6 . 93 . Marin-Padilla M , Parisi JE , Armstrong DL , Sargent SK , Kaplan JA . Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and e pilepsy . Acta Neuropathol (Berl) 2002 ; 103 : 321 \200\223 32 . 77 . Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus . J Comp Neurol 2001 ; 435 : 406 \200\223 17 . CHAPTER 5 De \201 nitions and Epidemiology of Epilepsy Shichuo Li , Ding Ding , and Jianzhong Wu symptoms include sudden and transitory abnormal phenomena such as alterations of consciousn ess, or involuntary motor, sensory, autonomic, or psychic events, perceived by the patient or an observer. Epileptic seizures, even if recurrent, are not always synon- ymous with epi lepsy per se . Traditionally, and based on strong epidemiological data supporting the disti nctions, certain conditions under which seizures occur are generally not considered to be e pi- lepsy proper, although they are still considered within a broader spectrum of seizure-r elated disorders: ( 1 ) solitary unprovoked epileptic seizures, or a single cluster occurri ng within a 24-hour period or as a single episode of status epilepticus (SE); ( 2 ) febrile seizures or neonatal seizures (occurring in infants less than 28 days of age); ( 3 ) seizu res \200\230in close temporal association with an acute sys- temic, metabolic or toxic ins ult or in association with an acute cen- tral nervous system (CNS) insult (infection, strok e, cranial trauma, intracerebral hemorrhage, or acute alcohol intoxication or with- drawal) \200\231, i.e. seizures not necessarily due to an established and \200\230enduring altera tion in the brain \200\231. Seizures due to such acute and transient conditions have also b een described as provoked or acute symptomatic epileptic seizures. In these cases, the inte rval between the insult and the seizure \200\224 which can be used to separate acute sympt omatic from unprovoked seizures \200\224 may vary according to the underlying clinical con dition ( 6 ). Worldwide, an estimated 50 million people have epilepsy and around 85 % of people with epil epsy live in developing countries. There are two million new cases occurring in the world e very year. Up to 70 % of people with epilepsy could lead normal lives if prop- erly treated , but for an overwhelming majority of patients this is not the case ( 1 ). Overall, epileps y contributed more than seven million disability-adjusted life years (DALYs) (0.5 % ) to th e global burden of disease in 2000 ( 2 ). Among neurological disorders, more than half of t he burden in DALYs is contributed by cerebrovascular disease. Epilepsy contributed approxim ately 8 % of the burden, following Alzheimer and other dementias (12 % ) and migraine (8.3 % ). It is apparent that close to 90 % of the worldwide burden of epilepsy is to be found i n developing regions, with more than half occurring in the 39 % of the global population li ving in countries with the highest levels of premature mortality and lowest levels of incom e ( 3 ). De \201 nitions of epilepsy and epileptic seizures In 2005, the International League Again st Epilepsy (ILAE) pro- posed a conceptual de \201 nition for clinicians diagnosing epilep sy: \200\230a disorder characterized by an enduring predisposition to generate epileptic s eizures and by neurobiologic, cognitive, psychological and social consequences of this cond ition. The de \201 nition requires the occurrence of at least one epileptic seizure \200 \231 ( 4 ). Evidence of recurrence may be the only information available to most epide- mio logical studies with which to identify the presence of an \200\230endur- ing predispositio n to seizures \200\231. Therefore, epilepsy is de \201 ned in practice as \200\230two or more unprovoked seizures occurring at least 24 hours apart \200\231 for the purpose of cond ucting most population-based studies of epilepsy epidemiology ( 5 ). This operational appro ach has the additional advantage of permitting comparison of epide- miological studies acro ss time periods. Etiology According to ILAE commission reports, etiology is partitioned into three categorie s: Remote symptomatic refers to epilepsy that occurs in association with an antecedent conditi on that has been demonstrated to increase the risk of developing epilepsy. Antecedent facto rs include history of stroke, brain malformation, cerebral palsy, history of bacterial meni ngitis or viral encephalitis, certain chromosomal and genetic disorders, and tumors. Epilep sy in the context of a progres- sive condition (e.g. neurodegenerative disease or an aggres sive tumor) is often considered a subgroup within the category of remote symptomatic. Active epilepsy indicates a person who is either currently being treated for epilepsy or wh ose most recent seizure has occurred within a time interval usually de \201 ned as the pas t 2 or 5 years ( 6 ). In low- and middle-income countries, active epilepsy may be de \201 ned over a 1-year period, due to problems in recalling dates beyond that period ( 7 \200 \22311 ). Idiopathic refers to a group of well-characterized disorders whose initial onset is concent rated during infancy, childhood, and ado- lescence. The intent of the term is to re \202 e ct a presumed genetic etiology in which the primary and often the sole manifestation is sei zures. Epileptic seizure is de \201 ned in principle as \200\230a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain \200\231 ( 4 ). Operationally, these signs or oxford textbook of epilepsy and epileptic seizures 52 contributed to advances in the treatment and management of seizures. Cryptogenic is meant to be viewed neutrally and to designate that the nature of the underly ing cause is as yet unknown; it may have a fundamental genetic defect at its core or it may be the consequence of a separate as yet unrecognized disorder. Diagnostic accuracy and case ascertainment Major problems in epilepsy epidemiology are diag nostic accuracy and case ascertainment ( 30 , 31 ). Epileptic seizures are pleomor- phic, a lthough usually stereotyped for a given individual. Unlike most neurological disorders, the majorities of patients with epi- lepsy do not have permanent physical signs and can be dia gnosed only by taking a history or by the chance observation of a seizure. Diagnosis of epi lepsy is essentially a discretionary judgment that may vary depending on the skill and expe rience of the diagnosti- cian and the quality of witness information available. Electro- en cephalography is useful in classifying epilepsy, but is of limited help in making the diagn osis. In practice, both false positive and false negative diagnoses are common. Even if the diagnosis of epi- lepsy is accurate, case ascertainment poses a variety of problems. Some patients with seizures may never seek medical attention because they ignore or misinterpret the symptoms, or indeed may be unaware of them. Some patients conceal or deny their seizur e history because of barriers of traditional prejudice, especially in less developed region s. It is likely, therefore, that epidemiological studies of epilepsy often miss patients un less sensitive screening techniques are included ( 26 ). The range of aetiologies for the development of epilepsy varies with age and geographic loc ation. Congenital, developmental, and genetic conditions are mostly associated with the dev elopment of epilepsy in childhood, adolescence, and early adulthood. Head trauma, CNS infec tions, and tumors may occur at any age and may lead to the development of epilepsy, althoug h tumors are more likely over the age of 40. Cerebrovascular disease (CVD) is the most comm on risk factor for epilepsy in people over the age of 60 years. Endemic infections are asso ciated with epilepsy in certain environ- ments, particularly in resource-poor countries, an d these include malaria, neurocysticercosis, paragonomiasis, and toxocariasis ( 4 , 12 \200 \22318 ). The presence of a family history of epilepsy seems to enhance other risk factors and this may suggest that the etiology of epilepsy is multifactorial ( 19 \200\22322 ). Bas ed on community-based studies, proportions of presumed identi \201 ed causes of epilepsy a re as follows: CVD 11 \200\22321 % ; trauma 2 \200\2236 % ; tumors 4 \200\2237 % ; infectio n 0 \200\2233 % , and idiopathic 54 \200\22365 % ( 23 \200\22325 ). It is evident that the successful detection of an aetiological factor depends upon the exte nt of investigation and unless this is stand- ardized and speci \201 ed in any study, eval uation of the results is prob- lematic ( 26 ). The use of the terms idiopathic epilepsy and cryptogenic epilepsy is a particular source of confusion. Thus, new terminology and concep ts advanced by the ILAE divide the causes of epilepsy into categories of structural/metabol ic, genetic, and unknown, corresponding roughly to the former categories of remote symptoma tic, idiopathic, and cryptogenic. The concepts and terminology were updated to keep them re levant in the con- text of increasing advances in genomics and neuroimaging and improved un derstanding of epilepsy ( 27 ). The incidence and prevalence of epilepsy The common standard measures of the frequency of e pilepsy in a population are incidence rate and prevalence rate: Incidence rate is the frequency with which new cases occur in a population. It is expressed as a frequency per standard population (e.g. 100,000) per time period (usually per year). Incidence density is also useful for estimating the incidence in dynamic populations, when the denominator is the sum of the person-year of the at-risk population. Incidence is infor mative about the rate of new cases regardless of the prognosis or cause of the disorder. Fo r aetiological and prognostic investigations, incidence-based studies are superior to preva lence-based studies ( 6 ). The overall incidence of epilepsy is generally taken to be aroun d 50 per 100,000 population per year (range 40 \200\22370 per 100,000 population per year) while the incidence of epilepsy in resource-poor countries is generally higher in the range of 100 \200\223190 cases per 100,000 population per year ( 32 \200\22337 ). It has been sh own that people from a socioeconomically deprived background are at higher risk of developi ng epilepsy ( 38 ). In indus- trialized countries, there is evidence of a decrease in the i ncidence in children and a simultanous increase in the elderly over the last three decades ( 39 , 40 ). Epidemiology Epidemiology is the study of the dynamics of a medical condition in terms of i ts distribution, determinants, and natural history in a population. It consists of three do mains: descriptive, analytical, and experimental epidemiology. Descriptive epidemiology con - cerns the vital statistics of a condition and is usually observational, with no designed control group. Analytical epidemiology attempts to establish associations and determinants of a condition, often by comparing individuals with the condition or risk factors for it wi th those without, for example, in cohort and case \200\223control studies. Studies under co nditions that allow an investigator to control relevant factors constitute experimental epi demiology ( 28 ). The epidemiology of epilepsy is largely based on descriptive and analytic al studies, as very little experimental work has been carried out for a number of reasons, including logistical and ethical considerations ( 26 ). Table 5. 1 presents \201 ndings from incidence studies of epilepsy worldwide. In North Am erica, age-adjusted incidence of epilepsy ranged from 16 per 100,000 person-years ( 41 ) to 51 per 100,000 person-years ( 24 ). The only incidence study that could be age- adjusted i n South America, conducted in rural Chile, reported the highest age-adjusted incidence in t he world (111 per 100,000 person-years) ( 42 ). Age- adjusted incidence of epilepsy in Euro pean studies ranged from 26 per 100,000 person-years in Norway ( 43 ) to 47 per 100,000 per son years in England ( 33 ). Only one incidence study that could be age-adjusted was conduc ted in India in Asia, this reported an age-adjusted incidence of 35 per The \201 rst landmark epidemiological study of epilepsy was con- ducted in 1959 by Leonar d T. Kurland and colleagues who reported population-based data from Rochester, Minnesota, U SA, over a 10-year period ( 29 ). Early epidemiological studies that followed from Kurland \200\231s work contributed substantially to our current understanding of epilepsy. Addition al studies exploring the Rochester longitudinal population-based data sets provided an evid ence base of the occurrence and prognosis of epilepsy that CHAPTER 5 definitions and epidemiology of epilepsy 53 100,000 person-years ( 44 ). In Africa, studies reported age-adjusted incidence of epilepsy of 51 per 100,000 in Tanzania ( 12 ) and 43 per 100,000 in Ethiopia ( 45 ). Table 5. 2 presents age-adjusted prevalence of epilepsy in studies that used door-to-door s urvey methodology worldwide. In the North American studies, the prevalence was 5.0 in New Y ork ( 48 ) and 7.1 per 1000 ( 49 ) in Mississippi. In Central and South America, the overal l prevalence ranged from 3.7 per 1000 in Argentina ( 50 ) to 22.2 per 1000 in Ecuador ( 51 ). Real differences in prevalence may be related to the presence of endemic conditions such as neu- rocysticercosis or malaria, the medical infrastructure in place, including availab ility of preventive regional health programs, and accessible local medical care. A region w hich has eradicated the porcine tapeworm, has established effective malaria prevention stra tegies, or has established immunization programs, can reduce or minimize risk factors assoc iated with epilepsy ( 52 ). In Europe, prevalence was low, 2.7 per 1000 and 3.3 per 1000, r espec- tively in each study conducted in Italy ( 53 , 54 ), when compared to a prevalence o f 7.0 per 1000 in the study conducted in the European region of Turkey ( 55 ). In contrast to the majority of studies con- ducted in Asia, the prevalence of 10.2 per 1000 in Asian Tu rkey ( 56 ) Point prevalence is the proportion of individuals in the popula- tion who are affected by a health condition at a single point in time, usually designated as a speci \201 c day. It is useful for indicating the degree of disease burden in a population. With epilepsy, the p oint prevalence of active epilepsy is typically considered of most interest ( 6 ). A pletho ra of studies has been made of the prevalence of epi- lepsy in many different settings and it has usually been found to be 4 \200\22310 per 1000 persons ( 26 ). Most large-scale stud ies of popula- tions in resource-poor countries have reported prevalence rates for active e pilepsy of 6 \200\22310 per 1,000; many of these studies have, how- ever, reported differen t rates for urban and rural areas, usually with higher rates in the latter ( 11 , 30 , 31 , 46 , 47 ). The differences seem unlikely to be artefactual or attributable to differential case ascer- tainment between regions as many of these studies used identical methods, stud y design, and diagnostic con \201 rmation in each area. Table 5.1 Incidence of epilepsy in population based studies of all ages worldwide Region Publication year (reference) Gender Population Number of cases Incidence (per 100,000 population) Crude Age-adjusted to 2000 US standard population North America Rochester, MN 1935 \200\22344 1993 ( 24 ) M > F 245,969 94 38 41 Rochester, MN 1945 \200\22354 1993 ( 24 ) M > F 282,452 142 50 49 Rochester, MN 1955 \200\22364 1993 ( 24 ) M > F 384,881 187 45 44 Rochester, MN 1965 \200\22374 1993 ( 24 ) M > F 516,903 182 35 36 Rochester, MN 1975 \200\22384 1993 ( 24 ) M > F 573,152 275 48 51 Texas 1999 ( 117 ) M > F 601,448 197 33 28 New York 2008 ( 41 ) M > F 279,677 82 15 16 Central and South America Chile 1992 ( 42 ) M > F 90,596 102 113 111 Europe England 1966 ( 118 ) \200\223 497,707 141 29 28 Norway 1974 ( 43 ) M > F 213,116 70 33 26 Italy 1983 ( 119 ) M > F 697,000 230 33 33 Faroes 1986 ( 120 ) M > F 452,584 194 43 37 Iceland 1996 ( 121 ) M > F 90,237 42 47 43 England 2000 ( 33 ) \200\223 100,230 46 46 47 Netherlands 2002 ( 34 ) M > F 316,828 94 30 29 Iceland 2005 ( 122 ) M > F 882,151 290 33 31 Asia India 1998 ( 44 ) M > F 64,963 32 49 35 Africa Tanzania 1992 ( 12 ) \200\223 165,684 122 73 51 Ethiopia 1997 ( 45 ) M > F 215,901 139 64 43 From Banerjee et al. ( 52 ). oxford textbook of epilepsy and epileptic seizures 54 Table 5.2 Age-adjusted prevalence of epilepsy in studies that used door-to-door survey meth odology worldwide Region Publication year (reference number) Gender Population Number of cases Prevalence (per 1000 population) Crude Age-adjusted to 2000 US standard population North America Mississippi 1986 ( 49 ) M > F 23,597 160 6.8 7.1 2007 ( 48 ) a M < F 208,301 42 5.2 5.0 New York Central and South America Ecuador 1985 ( 51 ) M < F 1113 19 17.1 22.2 Ecuador 1992 ( 46 ) M < F 72,121 575 8.0 9.1 5 b 22.6 11.4 Ecuador 1997 ( 123 ) M > F 221 Bolivia 1999 ( 124 ) M < F 10,124 112 11.1 14.0 Honduras 2005 ( 125 ) M < F 6473 100 15.4 16.0 Argentina 2007 ( 50 ) M < F 17,049 64 3.8 3.7 Europe Italy 1996 ( 53 ) M < F 9956 27 2.7 2.7 Italy 2001 ( 54 ) M > F 24,496 81 3.3 3.3 Turkey 2002 ( 55 ) M > F 2817 17 6.0 7.0 Asia China 1985 ( 61 ) M > F 63,195 289 4.6 4.4 India 1988 1988 ( 58 ) M > F 63,645 157 2.5 2.2 India 1988 ( 59 ) M > F 14,010 50 3.6 3.6 Pakistan 1997 ( 57 ) M < F 24,130 241 9.9 9.8 Turkey c 1997 ( 57 ) M > F 11,497 81 7.0 6.6 Turkey c 1999 ( 56 ) M > F 4803 49 10.2 10.2 India 2000 2000 ( 60 ) M > F 238,102 1,175 4.9 4.4 Saudi Arabia 2001 ( 126 ) M > F 23,700 155 6.5 5.1 Africa Nigeria 1982 ( 127 ) M < F 903 33 37 41.0 Nigeria 1987 ( 128 ) M < F 18,954 101 5.3 4.9 Nigeria 1989 ( 8 ) M < F 2925 18 6.2 4.7 Ethiopia 1990 ( 129 ) M > F 60,820 316 5.2 5.4 Tanzania 1992 ( 12 ) M < F 18,183 185 10.2 12.5 Tunisia 1993 ( 130 ) M > F 35,370 141 4.0 3.9 Kenya 1994 ( 131 ) M > F 7450 (5 + ) 30 4.0 3.7 Uganda 1996 ( 132 ) M < F 4743 61 12.9 9.2 Zambia 2004 ( 10 ) M > F 55,000 799 14.5 13.2 Tanzania 2005 ( 133 ) M > F 4905 42 8.6 6.8 Paci \201 c Islands Guam 1968 ( 134 ) \200\223 6967 16 2.3 2.7 a This study was done using random-digit dial methodology in the Northern Manhattan communi ty. A follow-up interview was administered to those who screened positive for epilepsy over the telephone. Epileptologists reviewed all information from interviews to determine whether each potentia l case was actually a case. b All 5 cases were between 7 \200\22314 years of age. c These s tudies were conducted in a region of Turkey that is geographically part of Asia. However, t he population may be more comparable to the western region of Turkey, which is part of Europe. From Banerjee et al. ( 52 ). CHAPTER 5 definitions and epidemiology of epilepsy 55 Death in people with epilepsy can be classi \201 ed into three groups: epilepsy-related de aths, deaths related to the underlying cause of the epilepsy, and deaths that are unrelated to the epilepsy or its underlying etiology (Table 5. 3 ) ( 84 ). The PMRs for epilepsy- re lated conditions range from 1 \200\22345 % ( 63 , 76 , 78 , 80 , 82 , 84 ). was higher than that reported in studies conducted in Pakistan, India, and China, where pre valence ranged from 2.2 \200\2234.4 per 1000 ( 57 \200\22361 ).