Epilepsien bei demenziellen und neurodegenerativen Erkrankungen

Zusammenfassung

Die Assoziation von Epilepsien zu neurodegenerativen demenziellen Erkrankungen ist bislang wenig untersucht, verdient jedoch schon aufgrund der demografischen Entwicklung, die eine Häufigkeitszunahme beider Erkrankungen vorhersagt, vermehrte Beachtung. Der Begriff der „Altersepilepsie”, durch den eine Einheitlichkeit der Pathogenese und Therapie suggeriert wird, wird jedoch den verschiedenen Aspekten der Epilepsien bei neurodegenerativen und demenziellen Erkrankungen nicht gerecht. Insbesondere die Demenz vom Alzheimer-Typ ist mit epileptischen Anfällen assoziiert, ein hinsichtlich Häufigkeit und Folgen unterschätztes (sozial-)medizinisches Problem. Bezüglich des Auftretens von Epilepsien bei anderen neurodegenerativen Erkrankungen lassen sich keine einheitlichen und umfassenden Aussagen über epidemiologische, pathophysiologische, klinisch-semiologische oder therapeutische Zusammenhänge treffen. Aus diesem Grund erscheint eine syndromale Klassifikation von Epilepsien bei der heterogenen Gruppe neurodegenerativer demenzieller Erkrankungen aktuell noch schwierig. Unsere Übersicht fasst die bisherig vorliegenden Daten über epidemiologische, differenzialdiagnostische, anfalls-semiologische, pathophysiologische und therapeutische Aspekte hinsichtlich Epilepsien bei demenziellen und neurodegenerativen Erkrankungen zusammen.

Abstract

The association between neurodegenerative disorders with dementia and epilepsies has received little attention. However, this connection deserves a higher level of alertness if only due to the expected demographic developments which suggest an increasing prevalence of each disease group. The frequently used term „epilepsy of the eldery” falsely suggests a uniform pathogenesis and therapy, but is clearly insufficient to reflect the different pathopysiological and therapeutic considerations of different neurodegenerative syndromes leading to epilepsy in elderly patients. Especially the frequent association of recurrent seizures and Alzheimer's disease is a problem whose important medical and social implications are often neglected. Concerning epilepsies in other neurodegenerative diseases, there is insufficient and incoherent evidence about epidemiological, pathophysiological, semiological or therapeutic connections and considerations. Therefore it seems difficult to propose a syndromal classification of epilepsies in the heterogeneous group of neurodegenerative disorders with dementia. This review outlines the available data about epidemiological, (differential) diagnostic, semiological, pathophysiological and therapeutic aspects of epilepsies in neurodegenerative disorders with dementia.

Schlüsselwörter

Epilepsie - Demenz - neurodegenerative Erkrankungen - Demenz vom Alzheimer-Typ

Key words

epilepsy - dementia - neurodegenerative disorders - dementia of the Alzheimer type

Literatur

• 1 Secretariat Population Division of the Department of Economic and Social Affairs of the United Nations .World Population Prospects: The 2006 Revision;. 2006
• 2 Hebert L E, Scherr P A, Bienias J L. et al . Alzheimer disease in the US population: prevalence estimates using the 2000 census.  Arch Neurology. 2003;  60 1119-1122
• 3 Krämer G. Epilepsien im höheren Lebensalter. Stuttgart, New York; Georg Thieme Verlag 1999
• 4 Tallis R, Hall G, Craig I. et al . How common are epileptic seizures in old age?.  Age Ageing. 1991;  20 442-448
• 5 Brust J CM. Seizures in the elderly. In: Lüders HO, Noachtar S, eds Epileptic seizures. New York; Churchill Livingstone 2000: 529-538
• 6 LaRoche S M, Helmers S L. Epilepsy in the elderly.  Neurologist. 2003;  9 241-249
• 7 Leppik I E, Coyd J C. Treatment of epilepsy in the elderly. In: Levy RH, Mattson RH, Meldrun BS, Perucca E, eds Antiepileptic Drugs. Philadelphia; Lippincott, Williams & Wilkins 2002: 149-168
• 8 Rowan A J. Epilepsy and the elderly.  Epilepsy Behav. 2000;  1 S12-S14
• 9 Stephen L J, Brodie M J. Epilepsy in elderly people.  Lancet. 2000;  355 1441-1446
• 10 Gaitatzis A, Carroll K, Majeed A. et al . The epidemiology of the comorbidity of epilepsy in the general population.  Epilepsia. 2004;  45 1613-1622
• 11 Bourdet S V, Gidal B E, Alldredge B K. Pharmacologic management of epilepsy in the elderly.  J Am Pharm Assoc (Wash). 2001;  41 421-436
• 12 Dickson D W. Neurodegeneration: the molecular pathology of dementia and movement disorders. Basel; ISN Neuropathology Press 2003
• 13 Bengel D, Supprian T, Lesch K P. Koinzidenz von Chorea Huntington und Epilepsie.  Nervenarzt. 1997;  68 270-273
• 14 Filla A, De Michele G, Cocozza S. et al . Early onset autosomal dominant dementia with ataxia, extrapyramidal features, and epilepsy.  Neurology. 2002;  58 922-928
• 15 Matsuura T, Achari M, Khajavi M. et al . Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy.  Ann Neurol. 1999;  45 407-411
• 16 Sperfeld A D, Collatz M B, Baier H. et al . FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation.  Ann Neurol. 1999;  46 708-715
• 17 Inazuki G, Baba K, Naito H. Electroencephalographic findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA).  Jpn J Psychiatry Neurol. 1989;  43 213-220
• 18 Nielsen J E, Sorensen S A, Hasholt L. et al . Dentatorubral-pallidoluysian atrophy. Clinical features of a five-generation Danish family.  Mov Disord. 1996;  11 533-541
• 19 Amatniek J C, Hauser W A, Delcastillo-Castaneda C. et al . Incidence and predictors of seizures in patients with Alzheimer's disease.  Epilepsia. 2006;  47 867-872
• 20 Hauser W A, Morris M L, Heston L L. et al . Seizures and myoclonus in patients with Alzheimer's disease.  Neurology. 1986;  36 1226-1230
• 21 Hesdorffer D C, Hauser W A, Annegers J F. et al . Dementia and adult-onset unprovoked seizures.  Neurology. 1996;  46 727-730
• 22 McAreavey M J, Ballinger B R, Fenton G W. Epileptic seizures in elderly patients with dementia.  Epilepsia. 1992;  33 657-660
• 23 Mendez M F, Catanzaro P, Doss R C. et al . Seizures in Alzheimer's disease: clinicopathologic study.  J Geriatr Psychiatry Neurol. 1994;  7 230-233
• 24 Risse S C, Lampe T H, Bird T D. et al . Myoclonus, seizures, and paratonia in Alzheimer disease.  Alzheimer Dis Assoc Disord. 1990;  4 217-225
• 25 Romanelli M F, Morris J C, Ashkin K. et al . Advanced Alzheimer's disease is a risk factor for late-onset seizures.  Arch Neurol. 1990;  47 847-850
• 26 Volicer L, Smith S, Volicer B J. Effect of seizures on progression of dementia of the Alzheimer type.  Dementia. 1995;  6 258-263
• 27 Lozsadi D A, Larner A J. Prevalence and causes of seizures at the time of diagnosis of probable Alzheimer's disease.  Dement Geriatr Cogn Disord. 2006;  22 121-124
• 28 Forsgren L, Bucht G, Eriksson S. et al . Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study.  Epilepsia. 1996;  37 224-229
• 29 Hatanpaa K J, Blass D M, Pletnikova O. et al . Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia.  Neurology. 2004;  63 538-542
• 30 Daniel S E, de Bruin V M, Lees A J. The clinical and pathological spectrum of Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy): a reappraisal.  Brain. 1995;  118 759-770
• 31 Nygaard T G, Duvoisin R C, Manocha M. et al . Seizures in progressive supranuclear palsy.  Neurology. 1989;  39 138-140
• 32 Mahapatra R K, Edwards M J, Schott J M. et al . Corticobasal degeneration.  Lancet Neurology. 2004;  3 736-743
• 33 Yakovlev P I. Epilepsy and parkinsonism.  N Engl J Med. 1928;  198 629-638
• 34 Bodenmann P, Ghika J, Van Melle G. et al . Neurological comorbidity in parkinsonism.  Rev Neurol (Paris). 2001;  157 45-54
• 35 Tagliati M, Perl D P, Drayer B. et al . Progressive dementia and gait disorder in a 78 year old woman.  J Neurol Neurosurg Psychiatry. 2000;  68 526-531
• 36 Vercueil L. Parkinsonism and epilepsy: case report and reappraisal of an old question.  Epilepsy Behav. 2000;  1 128-130
• 37 DeLong M R, Alexander G E, Georgopoulos A P. et al . Role of basal ganglia in limb movements.  Hum Neurobiol. 1984;  2 235-244
• 38 Norden A D, Blumenfeld H. The role of subcortical structures in human epilepsy.  Epilepsy Behav. 2002;  3 219-231
• 39 Chabardes S, Kahane P, Minotti L. et al . Deep brain stimulation in epilepsy with particular reference to the subthalamic nucleus.  Epileptic Disord. 2002;  4 (Suppl. 3) S83-93
• 40 Weiner M F, Hynan L S, Parikh B. et al . Can alzheimer's disease and dementias with Lewy bodies be distinguished clinically?.  J Geriatr Psychiatry Neurol. 2003;  16 245-250
• 41 Peset V, Castillo A, Brocalero A. et al . Epilepsy and dementia due to Lewy bodies.  Rev Neurol. 2001;  33 895-896
• 42 Quinn N. Multiple system atrophy – the nature of the beast.  J Neurol Neurosurg Psychiatry. 1989;  Suppl 78-89
• 43 Deransart C, Depaulis A. The control of seizures by the basal ganglia? A review of experimental data.  Epileptic Disord. 2002;  4 (Suppl. 3) S61-72
• 44 Brackenridge C J. Factors influencing dementia and epilepsy in Huntington's disease of early onset.  Acta Neurol Scand. 1980;  62 305-311
• 45 Siesling S, Vegter-van der Vlis M, Roos R A. Juvenile Huntington disease in the Netherlands.  Pediatr Neurol. 1997;  17 37-43
• 46 Ruocco H H, Lopes-Cendes I, Laurito T L. et al . Clinical presentation of juvenile Huntington disease.  Arq Neuropsiquiatr. 2006;  64 5-9
• 47 Gonzalez-Alegre P, Afifi A K. Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature.  J Child Neurol. 2006;  21 223-229
• 48 Subramony S H, Filla A. Autosomal dominant spinocerebellar ataxias ad infinitum?.  Neurology. 2001;  56 287-289
• 49 Warner T T, Lennox G G, Janota I. et al . Autosomal-dominant dentatorubropallidoluysian atrophy in the United Kingdom.  Mov Disord. 1994;  9 289-296
• 50 Iizuka R, Hirayama K, Maehara K A. Dentato-rubro-pallido-luysian atrophy: a clinico-pathological study.  J Neurol Neurosurg Psychiatry. 1984;  47 1288-1298
• 51 Remillard G, Andermann F, Blitzer L. et al . Electroencephalographic findings in Friedreich's ataxia.  Can J Neurol Sci. 1976;  3 309-312
• 52 Golomb M R, Illner A, Christensen C K. et al . A child with Friedreich's ataxia and epilepsy.  J Child Neurol. 2005;  20 248-250
• 53 Cokgor I, Rozear M, Morgenlander J C. Seizures and Creutzfeldt-Jakob disease. A case report and series review.  N C Med J. 1999;  60 108-109
• 54 Lee K, Haight E, Olejniczak P. Epilepsia partialis continua in Creutzfeldt-Jakob disease.  Acta Neurol Scand. 2000;  102 398-402
• 55 Fernandez-Torre J L, Solar D M, Astudillo A. et al . Creutzfeldt-Jakob disease and non-convulsive status epilepticus: a clinical and electroencephalographic follow-up study.  Clin Neurophysiol. 2004;  115 316-319
• 56 Karatas H, Dericioglu N, Kursun O. et al . Creutzfeldt-Jakob disease presenting as hyperparathyroidism and generalized tonic status epilepticus.  Clin EEG Neurosci. 2007;  38 203-206
• 57 Hung C I, Wang P S, Soong B W. et al . Blind source separation of concurrent disease-related patterns from EEG in Creutzfeldt-Jakob disease for assisting early diagnosis.  Ann Biomed Eng. 2007;  35 2168-2179
• 58 Floel A, Reilmann R, Frese A. et al . Anticonvulsants for Creutzfeldt-Jakob disease?.  Lancet. 2003;  361 224
• 59 Collins S, McLean C A, Masters C L. Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies.  J Clin Neurosci. 2001;  8 387-397
• 60 Haliloglu G, Chattopadhyay A, Skorodis L. et al . Spinal muscular atrophy with progressive myoclonic epilepsy: report of new cases and review of the literature.  Neuropediatrics. 2002;  33 314-319
• 61 Striano P, Boccella P, Sarappa C. et al . Spinal muscular atrophy and progressive myoclonic epilepsy: one case report and characteristics of the epileptic syndrome.  Seizure. 2004;  13 582-586
• 62 Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects.  Lancet Neurology. 2005;  4 239-248
• 63 Widdess-Walsh P, Prayson R A, Cohen B. et al . A 12-year-old girl with seizures and dementia.  Brain Pathol. 2007;  17 464-465, 474
• 64 Haltia M. The neuronal ceroid-lipofuscinoses: from past to present.  Biochim Biophys Acta. 2006;  1762 850-856
• 65 Gdynia H J, Sperfeld A D, Ludolph A C. Neuronale Zeroidlipofuszinosen des Erwachsenenalters.  Nervenarzt. 2007;  78 139-144
• 66 Gallus G N, Dotti M T, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene.  Neurol Sci. 2006;  27 143-149
• 67 Moller J C, Hamer H M, Oertel W H. et al . Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).  Seizure. 2002;  11 (Suppl. A) 303-305
• 68 Crespel A, Gonzalez V, Coubes P. et al . Senile myoclonic epilepsy of Genton: two cases in Down syndrome with dementia and late onset epilepsy.  Epilepsy research. 2007;  77 165-168
• 69 De Simone R, Daquin G, Genton P. Senile myoclonic epilepsy in Down syndrome: a video and EEG presentation of two cases.  Epileptic Disord. 2006;  8 223-227
• 70 Flierl-Hecht A, Pfafflin M, May T W. et al . Werden Epilepsien bei älteren Menschen übersehen?.  Nervenarzt. 2003;  74 691-698
• 71 Tatum 4th W O, Ross J, Cole A J. Epileptic pseudodementia.  Neurology. 1998;  50 1472-1475
• 72 Tombini M, Koch G, Placidi F. et al . Temporal lobe epileptic activity mimicking dementia: a case report.  Eur J Neurol. 2005;  12 805-806
• 73 Josephs K A, Wai D F, Parisi J E. Hippocampal sclerosis in a case of Alzheimer's disease-like dementia with late onset intractable epilepsy.  Eur J Neurol. 2003;  10 333-334
• 74 Lozsadi D A, Chadwick D W, Larner A J. Late-onset temporal lobe epilepsy with unilateral mesial temporal sclerosis and cognitive decline: A diagnostic dilemma.  Seizure. 2008;  17 473-476
• 75 Gallassi R, Morreale A, Di Sarro R. et al . Epileptic amnesic syndrome.  Epilepsia. 1992;  33 (Suppl. 6) S21-25
• 76 Palmini A L, Gloor P, Jones-Gotman M. Pure amnestic seizures in temporal lobe epilepsy. Definition, clinical symptomatology and functional anatomical considerations.  Brain. 1992;  115 749-769
• 77 Butler C R, Graham K S, Hodges J R. et al . The syndrome of transient epileptic amnesia.  Ann Neurol. 2007;  61 587-598
• 78 Gallassi R. Epileptic amnesic syndrome: an update and further considerations.  Epilepsia. 2006;  47 (Suppl. 2) 103-105
• 79 Butler C R, Zeman A Z. Recent insights into the impairment of memory in epilepsy: transient epileptic amnesia, accelerated long-term forgetting and remote memory impairment.  Brain. 2008;  131 2243-2263
• 80 Menendez M. Down syndrome, Alzheimer's disease and seizures.  Brain Dev. 2005;  27 246-252
• 81 Griffith H R, Martin R C, Bambara J K. et al . Older adults with epilepsy demonstrate cognitive impairments compared with patients with amnestic mild cognitive impairment.  Epilepsy Behav. 2006;  8 161-168
• 82 Ezquerra M, Carnero C, Blesa R. et al . A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures.  Neurology. 1999;  52 566-570
• 83 Diaz-Arrastia R, Gong Y, Fair S. et al . Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele.  Archives of neurology. 2003;  60 818-822
• 84 Armon C, Peterson G W, Liwnicz B H. Alzheimer's disease underlies some cases of complex partial status epilepticus.  J Clin Neurophysiol. 2000;  17 511-518
• 85 Janszky J, Hoppe M, Clemens Z. et al . Spike frequency is dependent on epilepsy duration and seizure frequency in temporal lobe epilepsy.  Epileptic Disord. 2005;  7 355-359
• 86 Krauss G L, Abdallah A, Lesser R. et al . Clinical and EEG features of patients with EEG wicket rhythms misdiagnosed with epilepsy.  Neurology. 2005;  64 1879-1883
• 87 Mushtaq R, Van Cott A C. Benign EEG variants.  Am J Electroneurodiagnostic Technol. 2005;  45 88-101
• 88 Tatum 4th W O, Husain A M, Benbadis S R. et al . Normal adult EEG and patterns of uncertain significance.  J Clin Neurophysiol. 2006;  23 194-207
• 89 Ferreri F, Pauri F, Pasqualetti P. et al . Motor cortex excitability in Alzheimer's disease: a transcranial magnetic stimulation study.  Ann Neurol. 2003;  53 102-108
• 90 Di Lazzaro V, Oliviero A, Tonali P A. et al . Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation.  Neurology. 2002;  59 392-397
• 91 Di Lazzaro V, Oliviero A, Pilato F. et al . Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 555-559
• 92 Palop J J, Chin J, Roberson E D. et al . Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease.  Neuron. 2007;  55 697-711
• 93 Cabrejo L, Guyant-Marechal L, Laquerriere A. et al . Phenotype associated with APP duplication in five families.  Brain. 2006;  129 2966-2976
• 94 Takao M, Ghetti B, Murrell J R. et al . Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures.  J Neuropathol Exp Neurol. 2001;  60 1137-1152
• 95 Hogh P, Smith S J, Scahill R I. et al . Epilepsy presenting as AD: neuroimaging, electroclinical features, and response to treatment.  Neurology. 2002;  58 298-301
• 96 Garrard J, Harms S, Hardie N. et al . Antiepileptic drug use in nursing home admissions.  Ann Neurol. 2003;  54 75-85
• 97 Cameron H, Macphee G J. Anticonvulsant therapy in the elderly – a need for placebo controlled trials.  Epilepsy Res. 1995;  21 149-157
• 98 Brodie M J, Overstall P W, Giorgi L. Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group.  Epilepsy Res. 1999;  37 81-87
• 99 Faught E. Monotherapy in adults and elderly persons.  Neurology. 2007;  69 S3-9
• 100 Gidal B E. Antiepileptic drug formulation and treatment in the elderly: biopharmaceutical considerations.  Int Rev Neurobiol. 2007;  81 299-311
• 101 Perucca E, Aldenkamp A, Tallis R. et al . Role of valproate across the ages. Treatment of epilepsy in the elderly.  Acta Neurol Scand Suppl. 2006;  184 28-37
• 102 Leppik I E. Epilepsy in the elderly.  Epilepsia. 2006;  47 (Suppl. 1) 65-70
• 103 Thomas S V, Pradeep K S, Rajmohan S J. First ever seizures in the elderly: a seven-year follow-up study.  Seizure. 1997;  6 107-110
• 104 Meador K J, Loring D W, Allen M E. et al . Comparative cognitive effects of carbamazepine and phenytoin in healthy adults.  Neurology. 1991;  41 1537-1540
• 105 Meador K J, Loring D W, Huh K. et al . Comparative cognitive effects of anticonvulsants.  Neurology. 1990;  40 391-394
• 106 Meador K J, Loring D W, Abney O L. et al . Effects of carbamazepine and phenytoin on EEG and memory in healthy adults.  Epilepsia. 1993;  34 153-157
• 107 Meador K J, Loring D W, Moore E E. et al . Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults.  Neurology. 1995;  45 1494-1499
• 108 Martin R, Kuzniecky R, Ho S. et al . Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults.  Neurology. 1999;  52 321-327
• 109 Aldenkamp A P, Baker G, Mulder O G. et al . A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures.  Epilepsia. 2000;  41 1167-1178
• 110 Aldenkamp A P, De Krom M, Reijs R. Newer antiepileptic drugs and cognitive issues.  Epilepsia. 2003;  44 (Suppl. 4) 21-29
• 111 Granger A S. Ginkgo biloba precipitating epileptic seizures.  Age Ageing. 2001;  30 523-525
• 112 Peltz G, Pacific D M, Noviasky J A. et al . Seizures associated with memantine use.  Am J Health Syst Pharm. 2005;  62 420-421
• 113 Babic T, Zurak N. Convulsions induced by donepezil.  J Neurol Neurosurg Psychiatry. 1999;  66 410
• 114 Pisani F, Oteri G, Costa C. et al . Effects of psychotropic drugs on seizure threshold.  Drug Saf. 2002;  25 91-110
• 115 Foster R, Olajide D. A case of clozapine-induced tonic-clonic seizures managed with valproate: implications for clinical care.  J Psychopharmacol. 2005;  19 93-96
• 116 Hedges D W, Jeppson K G. New-onset seizure associated with quetiapine and olanzapine.  Ann Pharmacother. 2002;  36 437-439
• 117 Dogu O, Sevim S, Kaleagasi H S. Seizures associated with quetiapine treatment.  Ann Pharmacother. 2003;  37 1224-1227
• 118 Lee J W, Crismon M L, Dorson P G. Seizure associated with olanzapine.  Ann Pharmacother. 1999;  33 554-556
• 119 Woolley J, Smith S. Lowered seizure threshold on olanzapine.  Br J Psychiatry. 2001;  178 85-86
• 120 Aarts J H, Binnie C D, Smit A M. et al . Selective cognitive impairment during focal and generalized epileptiform EEG activity.  Brain. 1984;  107 293-308
• 121 Jokeit H, Ebner A. Long-term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study.  J Neurol Neurosurg Psychiatry. 1999;  67 44-50
• 122 Binnie C D. Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG?.  Lancet Neurology. 2003;  2 725-730
• 123 Briellmann R S, Berkovic S F, Syngeniotis A. et al . Seizure-associated hippocampal volume loss: a longitudinal magnetic resonance study of temporal lobe epilepsy.  Ann Neurol. 2002;  51 641-644
• 124 Berg A T, Langfitt J, Shinnar S. et al . How long does it take for partial epilepsy to become intractable?.  Neurology. 2003;  60 186-190