Download PDF
Semin Neurol 2015; 35(03): 193-200
DOI: 10.1055/s-0035-1552618
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hippocampal Sclerosis: Causes and Prevention

Matthew Charles Walker
1   Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
10 June 2015 (online)

   Permissions and Reprints

Abstract

Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.

In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus.

Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets.

Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures.

Keywords

hippocampal sclerosis - status epileptics - epilepsy - neuroprotection
 

  • References

  • 1 Bouchet C, Cazavieilh J. De L'epilpsie consideree dans ses raports avec l'alienation mentale. Recherche sur la nature et le siege de ces deux maladies. Arch Gen Med. 1825; 9: 510-542
    PubMedGoogle Scholar
  • 2 Sommer W. Erkrankung des ammonshornes als aetiologisches moment der epilepsie. Arch Psychiatr Nervenkr 1880; 10: 631-675
    CrossrefPubMedGoogle Scholar
  • 3 Van Paesschen W, Duncan JS, Stevens JM, Connelly A. Longitudinal quantitative hippocampal magnetic resonance imaging study of adults with newly diagnosed partial seizures: one-year follow-up results. Epilepsia 1998; 39 (6) 633-639
    CrossrefPubMedGoogle Scholar
  • 4 Blümcke I, Spreafico R. Cause matters: a neuropathological challenge to human epilepsies. Brain Pathol 2012; 22 (3) 347-349
    CrossrefPubMedGoogle Scholar
  • 5 Walker M, Chan D, Thom M, Hippocampus and human disease. In: Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J. , eds. The Hippocampus Book. Oxford: Oxford University Press; 2007: 769-812
    Google Scholar
  • 6 Blümcke I, Thom M, Aronica E , et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on diagnostic methods. Epilepsia 2013; 54 (7) 1315-1329
    CrossrefPubMedGoogle Scholar
  • 7 Wyler AR, Curtis Dohan F, Schweitzer JB, Berry AD. A grading system for mesial temporal pathology (hippocampal sclerosis) from anterior temporal lobectomy. J Epilepsy 1992; 5 (4) 220-225
    CrossrefPubMedGoogle Scholar
  • 8 Thom M, Liagkouras I, Elliot KJ , et al. Reliability of patterns of hippocampal sclerosis as predictors of postsurgical outcome. Epilepsia 2010; 51 (9) 1801-1808
    CrossrefPubMedGoogle Scholar
  • 9 Watson C, Nielsen SL, Cobb C, Burgerman R, Williamson B. Pathological grading system for hippocampal sclerosis: correlation with magnetic resonance imaging-based volume measurements of the hippocampus. J Epilepsy 1996; 9 (1) 56-64
    CrossrefPubMedGoogle Scholar
  • 10 Schoene-Bake J-C, Keller SS, Niehusmann P , et al. In vivo mapping of hippocampal subfields in mesial temporal lobe epilepsy: relation to histopathology. Hum Brain Mapp 2014; 35 (9) 4718-4728
    CrossrefPubMedGoogle Scholar
  • 11 Borelli P, Shorvon SD, Stevens JM, Smith SJ, Scott CA, Walker MC. Extratemporal ictal clinical features in hippocampal sclerosis: their relationship to the degree of hippocampal volume loss and to the outcome of temporal lobectomy. Epilepsia 2008; 49 (8) 1333-1339
    CrossrefPubMedGoogle Scholar
  • 12 Bernasconi N, Bernasconi A, Caramanos Z, Antel SB, Andermann F, Arnold DL. Mesial temporal damage in temporal lobe epilepsy: a volumetric MRI study of the hippocampus, amygdala and parahippocampal region. Brain 2003; 126 (Pt 2) 462-469
    CrossrefPubMedGoogle Scholar
  • 13 Yilmazer-Hanke DM, Wolf HK, Schramm J, Elger CE, Wiestler OD, Blümcke I. Subregional pathology of the amygdala complex and entorhinal region in surgical specimens from patients with pharmacoresistant temporal lobe epilepsy. J Neuropathol Exp Neurol 2000; 59 (10) 907-920
    CrossrefPubMedGoogle Scholar
  • 14 Bernasconi N, Bernasconi A, Caramanos Z , et al. Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes. Neurology 2001; 56 (10) 1335-1339
    PubMedGoogle Scholar
  • 15 Jones RS. Ictal epileptiform events induced by removal of extracellular magnesium in slices of entorhinal cortex are blocked by baclofen. Exp Neurol 1989; 104 (2) 155-161
    CrossrefPubMedGoogle Scholar
  • 16 Sinjab B, Martinian L, Sisodiya SM, Thom M. Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: a postmortem study. Epilepsia 2013; 54 (12) 2125-2133
    CrossrefPubMedGoogle Scholar
  • 17 Barron DS, Fox PM, Laird AR, Robinson JL, Fox PT. Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: a VBM meta-analysis. Neuroimage Clin 2012; 2: 25-32
    PubMedGoogle Scholar
  • 18 Coan AC, Campos BM, Yasuda CL , et al. Frequent seizures are associated with a network of gray matter atrophy in temporal lobe epilepsy with or without hippocampal sclerosis. PLoS ONE 2014; 9 (1) e85843
    CrossrefPubMedGoogle Scholar
  • 19 Keller SS, Richardson MP, Schoene-Bake J-C , et al. Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy. Ann Neurol 2015; ; Epub ahead of print
    PubMedGoogle Scholar
  • 20 Pfleger L. Beobachtungen uber schrumpfung und sclerose des ammonshornes bei epilepsie. Allg Zeitschrift für Psychiatr 1880; 36: 359-365
    PubMedGoogle Scholar
  • 21 DeGiorgio CM, Tomiyasu U, Gott PS, Treiman DM. Hippocampal pyramidal cell loss in human status epilepticus. Epilepsia 1992; 33 (1) 23-27
    CrossrefPubMedGoogle Scholar
  • 22 Corsellis JA, Bruton CJ. Neuropathology of status epilepticus in humans. Adv Neurol 1983; 34: 129-139
    PubMedGoogle Scholar
  • 23 Thom M, Zhou J, Martinian L, Sisodiya S. Quantitative post-mortem study of the hippocampus in chronic epilepsy: seizures do not inevitably cause neuronal loss. Brain 2005; 128 (Pt 6) 1344-1357
    CrossrefPubMedGoogle Scholar
  • 24 French JA, Williamson PD, Thadani VM , et al. Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Ann Neurol 1993; 34 (6) 774-780
    CrossrefPubMedGoogle Scholar
  • 25 Davies KG, Hermann BP, Dohan Jr FC, Foley KT, Bush AJ, Wyler AR. Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients. Epilepsy Res 1996; 24 (2) 119-126
    CrossrefPubMedGoogle Scholar
  • 26 Lewis DV, Barboriak DP, MacFall JR, Provenzale JM, Mitchell TV, VanLandingham KE. Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions. Prog Brain Res 2002; 135: 263-278
    PubMedGoogle Scholar
  • 27 Lewis DV, Shinnar S, Hesdorffer DC , et al; FEBSTAT Study Team. Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Ann Neurol 2014; 75 (2) 178-185
    CrossrefPubMedGoogle Scholar
  • 28 Yoong M, Martinos MM, Chin RF, Clark CA, Scott RC. Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures. Epilepsia 2013; 54 (12) 2108-2115
    CrossrefPubMedGoogle Scholar
  • 29 Lowenstein DH, Thomas MJ, Smith DH, McIntosh TK. Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci 1992; 12 (12) 4846-4853
    PubMedGoogle Scholar
  • 30 Pavlov I, Huusko N, Drexel M , et al. Progressive loss of phasic, but not tonic, GABAA receptor-mediated inhibition in dentate granule cells in a model of post-traumatic epilepsy in rats. Neuroscience 2011; 194: 208-219
    CrossrefPubMedGoogle Scholar
  • 31 Vespa PM, McArthur DL, Xu Y , et al. Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 2010; 75 (9) 792-798
    CrossrefPubMedGoogle Scholar
  • 32 Kasperaviciute D, Catarino CB, Matarin M , et al; UK Brain Expression Consortium. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A. Brain 2013; 136 (Pt 10) 3140-3150
    CrossrefPubMedGoogle Scholar
  • 33 Blümcke I, Thom M, Wiestler OD. Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol 2002; 12 (2) 199-211
    PubMedGoogle Scholar
  • 34 Baulac M, De Grissac N, Hasboun D , et al. Hippocampal developmental changes in patients with partial epilepsy: magnetic resonance imaging and clinical aspects. Ann Neurol 1998; 44 (2) 223-233
    CrossrefPubMedGoogle Scholar
  • 35 Fernández G, Effenberger O, Vinz B , et al. Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology 1998; 50 (4) 909-917
    CrossrefPubMedGoogle Scholar
  • 36 Hardiman O, Burke T, Phillips J , et al. Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy. Neurology 1988; 38 (7) 1041-1047
    CrossrefPubMedGoogle Scholar
  • 37 Cendes F, Cook MJ, Watson C , et al. Frequency and characteristics of dual pathology in patients with lesional epilepsy. Neurology 1995; 45 (11) 2058-2064
    CrossrefPubMedGoogle Scholar
  • 38 Li LM, Cendes F, Andermann F , et al. Surgical outcome in patients with epilepsy and dual pathology. Brain 1999; 122 (Pt 5) 799-805
    CrossrefPubMedGoogle Scholar
  • 39 Briellmann RS, Berkovic SF, Syngeniotis A, King MA, Jackson GD. Seizure-associated hippocampal volume loss: a longitudinal magnetic resonance study of temporal lobe epilepsy. Ann Neurol 2002; 51 (5) 641-644
    CrossrefPubMedGoogle Scholar
  • 40 Janszky J, Janszky I, Schulz R , et al. Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome. Brain 2005; 128 (Pt 2) 395-404
    PubMedGoogle Scholar
  • 41 Bianchin MM, Velasco TR, Santos AC, Sakamoto AC. On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship?. Pathog Glob Health 2012; 106 (5) 280-285
    CrossrefPubMedGoogle Scholar
  • 42 Davies KG, Hermann BP, Wyler AR. Surgery for intractable epilepsy secondary to viral encephalitis. Br J Neurosurg 1995; 9 (6) 759-762
    CrossrefPubMedGoogle Scholar
  • 43 Epstein LG, Shinnar S, Hesdorffer DC , et al; FEBSTAT study team. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia 2012; 53 (9) 1481-1488
    CrossrefPubMedGoogle Scholar
  • 44 Vincent A, Buckley C, Schott JM , et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004; 127 (Pt 3) 701-712
    CrossrefPubMedGoogle Scholar
  • 45 Wagner J, Witt J-A, Helmstaedter C, Malter MP, Weber B, Elger CE. Automated volumetry of the mesiotemporal structures in antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatry 2014; ; (e-pub ahead of print)
    PubMedGoogle Scholar
  • 46 Meldrum B. Excitotoxicity and epileptic brain damage. Epilepsy Res 1991; 10 (1) 55-61
    CrossrefPubMedGoogle Scholar
  • 47 Collins RC, Lothman EW, Olney JW. Status epilepticus in the limbic system: biochemical and pathological changes. Adv Neurol 1983; 34: 277-288
    PubMedGoogle Scholar
  • 48 Tanaka H, Grooms SY, Bennett MV, Zukin RS. The AMPAR subunit GluR2: still front and center-stage. Brain Res 2000; 886 (1-2) 190-207
    CrossrefPubMedGoogle Scholar
  • 49 Weiss JH, Sensi SL. Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci 2000; 23 (8) 365-371
    CrossrefPubMedGoogle Scholar
  • 50 Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 1994; 330 (9) 613-622
    CrossrefPubMedGoogle Scholar
  • 51 Walker M. Status epilepticus: an evidence based guide. BMJ 2005; 331 (7518) 673-677
    CrossrefPubMedGoogle Scholar
  • 52 Jimenez-Mateos EM, Hatazaki S, Johnson MB , et al. Hippocampal transcriptome after status epilepticus in mice rendered seizure damage-tolerant by epileptic preconditioning features suppressed calcium and neuronal excitability pathways. Neurobiol Dis 2008; 32 (3) 442-453
    CrossrefPubMedGoogle Scholar
  • 53 Ostendorf AP, Wong M. mTOR Inhibition in Epilepsy: Rationale and Clinical Perspectives. CNS Drugs 2015; 29 (2) 91-99
    CrossrefPubMedGoogle Scholar
  • 54 Cardone MH, Roy N, Stennicke HR , et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998; 282 (5392) 1318-1321
    CrossrefPubMedGoogle Scholar
  • 55 Datta SR, Dudek H, Tao X , et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91 (2) 231-241
    CrossrefPubMedGoogle Scholar
  • 56 Brunet A, Bonni A, Zigmond MJ , et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96 (6) 857-868
    CrossrefPubMedGoogle Scholar
  • 57 Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 2010; 11 (10) 682-696
    CrossrefPubMedGoogle Scholar
  • 58 Kovac S, Domijan A-M, Walker MC, Abramov AY. Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation. Cell Death Dis 2014; 5: e1442
    CrossrefPubMedGoogle Scholar
  • 59 Baird L, Dinkova-Kostova AT. The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol 2011; 85 (4) 241-272
    CrossrefPubMedGoogle Scholar
  • 60 Milder JB, Liang L-P, Patel M. Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet. Neurobiol Dis 2010; 40 (1) 238-244
    CrossrefPubMedGoogle Scholar
  • 61 Delgado-Esteban M, Martin-Zanca D, Andres-Martin L, Almeida A, Bolaños JP. Inhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathway. J Neurochem 2007; 102 (1) 194-205
    CrossrefPubMedGoogle Scholar
  • 62 Hetman M, Gozdz A. Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. Eur J Biochem 2004; 271 (11) 2050-2055
    CrossrefPubMedGoogle Scholar
  • 63 Luo Y, DeFranco DB. Opposing roles for ERK1/2 in neuronal oxidative toxicity: distinct mechanisms of ERK1/2 action at early versus late phases of oxidative stress. J Biol Chem 2006; 281 (24) 16436-16442
    CrossrefPubMedGoogle Scholar
  • 64 Treiman DM, Walker MC. Treatment of seizure emergencies: convulsive and non-convulsive status epilepticus. Epilepsy Res 2006; 68 (Suppl. 01) S77-S82
    PubMedGoogle Scholar
  • 65 Meldrum BS. Implications for neuroprotective treatments. Prog Brain Res 2002; 135: 487-495
    PubMedGoogle Scholar
  • 66 Fujikawa DG, Daniels AH, Kim JS. The competitive NMDA receptor antagonist CGP 40116 protects against status epilepticus-induced neuronal damage. Epilepsy Res 1994; 17 (3) 207-219
    CrossrefPubMedGoogle Scholar
  • 67 Rowley S, Patel M. Mitochondrial involvement and oxidative stress in temporal lobe epilepsy. Free Radic Biol Med 2013; 62: 121-131
    CrossrefPubMedGoogle Scholar
  • 68 Henshall DC, Simon RP. Epilepsy and apoptosis pathways. J Cereb Blood Flow Metab 2005; 25 (12) 1557-1572
    CrossrefPubMedGoogle Scholar
  • 69 Fujikawa DG. Prolonged seizures and cellular injury: understanding the connection. Epilepsy Behav 2005; 7 (Suppl. 03) S3-S11
    CrossrefPubMedGoogle Scholar
  • 70 Narkilahti S, Pirttilä TJ, Lukasiuk K, Tuunanen J, Pitkänen A. Expression and activation of caspase 3 following status epilepticus in the rat. Eur J Neurosci 2003; 18 (6) 1486-1496
    CrossrefPubMedGoogle Scholar
  • 71 Kovac S, Abramov AY, Walker MC. Energy depletion in seizures: anaplerosis as a strategy for future therapies. Neuropharmacology 2013; 69: 96-104
    CrossrefPubMedGoogle Scholar
  • 72 Vezzani A, Aronica E, Mazarati A, Pittman QJ. Epilepsy and brain inflammation. Exp Neurol 2013; 244: 11-21
    CrossrefPubMedGoogle Scholar
  • 73 Pitkänen A, Kubova H. Antiepileptic drugs in neuroprotection. Expert Opin Pharmacother 2004; 5 (4) 777-798
    CrossrefPubMedGoogle Scholar
  • 74 Rice AC, Floyd CL, Lyeth BG, Hamm RJ, DeLorenzo RJ. Status epilepticus causes long-term NMDA receptor-dependent behavioral changes and cognitive deficits. Epilepsia 1998; 39 (11) 1148-1157
    CrossrefPubMedGoogle Scholar
  • 75 Prasad A, Williamson JM, Bertram EH. Phenobarbital and MK-801, but not phenytoin, improve the long-term outcome of status epilepticus. Ann Neurol 2002; 51 (2) 175-181
    CrossrefPubMedGoogle Scholar
  • 76 Brandt C, Potschka H, Löscher W, Ebert U. N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy. Neuroscience 2003; 118 (3) 727-740
    CrossrefPubMedGoogle Scholar