Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
    • Education
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Genetics
    • Neuroimmunology & Neuroinflammation
    • Education
  • Online Sections
    • Neurology Video Journal Club
    • Inclusion, Diversity, Equity, Anti-racism, & Social Justice (IDEAS)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit a Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in
  • Log out

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
  • Log out
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Residents & Fellows

Share

January 01, 1999; 52 (1) Articles

Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures

W.H. Theodore, S. Bhatia, J. Hatta, S. Fazilat, C. DeCarli, S.Y. Bookheimer, W.D. Gaillard
First published January 1, 1999, DOI: https://doi.org/10.1212/WNL.52.1.132
W.H. Theodore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Bhatia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Hatta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Fazilat
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. DeCarli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S.Y. Bookheimer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W.D. Gaillard
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures
W.H. Theodore, S. Bhatia, J. Hatta, S. Fazilat, C. DeCarli, S.Y. Bookheimer, W.D. Gaillard
Neurology Jan 1999, 52 (1) 132; DOI: 10.1212/WNL.52.1.132

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
571

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Background: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration.

Objective: To determine whether epilepsy duration is related to HF atrophy.

Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes.

Results: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration.

Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.

Pathologicand clinical studies have suggested that repeated complex partial seizures (CPS) of temporal lobe origin might induce progressive neuronal injury.1,2 There have been limited noninvasive methods to detect such injury. MRI hippocampal volume measurements (vMRI) reliably identify hippocampal formation (HF) atrophy, which predicts the location of the epileptogenic zone, in patients with temporal lobe epilepsy (TLE).3-5 Quantitative measurements of HF volume reduction are related to cell loss in pathologic specimens as well as clinical measures such as the Wechsler Memory Scale.6-9 It is very difficult to obtain accurate seizure counts over many years, but epilepsy duration might serve as a surrogate marker in patients with persistent TLE.

Some previous vMRI studies have suggested that longer epilepsy duration was associated with smaller HF volume ipsilateral to the epileptic focus,4 whereas others found a relation to a history of complicated febrile seizures (FS) but not duration.10 Evidence for a deleterious effect of persistent seizures would argue for more aggressive drug therapy or early surgery. We studied 35 patients referred to the National Institutes of Health (NIH) Clinical Epilepsy Section for uncontrolled CPS who had EEG and MRI evidence of temporal lobe epileptogenic zones.

Methods.

The patients (mean age 34.8 ± 10.2 years; 19 men) had been referred to the Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, for evaluation of uncontrolled partial seizures. Patients were selected for inclusion if ictal video-EEG telemetry with sphenoidal electrodes showed CPS with a temporal lobe epileptogenic zone. Because MRI volumetric studies were the dependent variable, they were not used as an inclusion criterion. Patients with evidence of a mass lesion were excluded. Twenty-two patients had surgery, and seven had invasive electrode studies. Mean age at seizure onset was 11.4 ± 5.9 years, and epilepsy duration was 23.1 ± 11.4 years. Detailed histories were obtained from patients, their families, and medical records. All patients had a history of secondary generalization. Nine patients were considered to have had initial “prolonged or complex” FS (FS+)—a seizure associated with fever occurring before the onset of afebrile seizures and lasting longer than 15 minutes, with focal features, or followed by transient or persistent neurologic abnormalities.11 FS− patients could have a history of simple FS, as defined by Nelson and Ellenberg.11 FS+ and FS− patients did not differ in epilepsy duration, age at seizure onset, or age at scan.

Contiguous coronal MRIs with a 2-mm slice thickness were obtained on a GE Signa 1.5-T MR scanner (GE Medical Systems, Milwaukee, WI). Scanning sequence was repeat time (TR) 24 msec, echo time (TE) 5 msec with a flip angle of 45°, field of view 24 × 24 cm with a matrix of 256 × 256. The voxel size was 0.9375 × 0.9375 × 2 mm3. Images were transferred to a VAX station and analyzed using the Medical Imaging Retrieval, Analysis and Graphics software (MIRAGE, NIH, Bethesda, MD). HF, temporal lobe, and whole brain volumes were drawn on consecutive images as described previously.12 The hippocampus was outlined in its entire extent, from the pes hippocampi anteriorly to the fasciolar gyrus. The posterior limit of the hippocampus corresponded anatomically to the region of the pulvinar. The margins of the body of the hippocampus were defined superiorly as the choroidal fissure curving laterally along the medial boundary of the temporal horn, then medially along the gray matter of the hippocampus, including the medial-most part of the subiculum where the hippocampus joins the parahippocampal gyrus. Anteriorly the pes was distinguished from the amygdala, which is close to the antero-superior aspect of the pes near the tip of temporal horn and the uncus. Pixel points were summed from successive pictures to calculate structure volumes. HF volume images had 15 slices.

We also calculated left/right HF volume ratios, which are less sensitive to variations in head size, volumes of intracranial structures, and gender. A ratio less than 1 suggests left HF atrophy, and greater than 1 suggests right HF atrophy. We scanned 19 normal volunteers (10 women, 9 men). Because there was no difference between left and right HF volumes we calculated a mean normal bilateral HF volume measure.

Statistical analysis was performed on a personal computer using Systat 7.0 (SPSS Inc., Chicago, IL). Student’s t-tests, analysis of variance, and multiple regression analyses were performed for FS+, age at study, age at afebrile seizure onset, epilepsy duration, and the ratio between duration and age at study. Because men and women were equally represented among both patients and controls, we did not make separate gender comparisons.

Results.

Mean HF volume ipsilateral to the focus was lower than HF volume contralateral to the epileptogenic zone identified by ictal video-EEG monitoring: 2.73 ± 0.67 versus 3.24 ± 0.53 cm3 (paired t-test = 5.384; p < 0.0001). FS+ patients had smaller HF volume than did FS− patients ipsilateral but not contralateral to the epileptogenic zones, as well as a lower ipsilateral/contralateral ratio (table).

View this table:
  • View inline
  • View popup
Table 1.

Effect of complex febrile seizures on HF volume

Compared with our normal controls (mean 3.29 ± 0.34 cm3), FS+ patients had small ipsilateral HF volume (p < 0.001) and a nonsignificant trend toward small contralateral HF volume (0.10 < p < 0.15). FS− patients had smaller HF volume only ipsilateral to the focus (p < 0.002). The FS+ group was too small to divide into men and women, but separate sex comparisons for the FS− group did not affect the results.

In simple regressions, epilepsy duration, but not age at scan or seizure onset, was significantly related to HF volume ipsilateral to the epileptogenic zone (R2 = 0.172, F = 6.66, p < 0.02) and to the ipsilateral/contralateral ratio (R2 = 0.154, F = 6.184, p < 0.02) (figures 1 through 3⇓⇓). HF volume contralateral to the focus tended to be smaller among FS+ than it was among FS− patients or controls (see table). When the effect of FS and duration was studied together, duration remained a significant variable for ipsilateral HF volume, although it had less weight (F = 4.997, p < 0.04) than did FS+ history (F = 9.691, p < 0.005). Neither age at afebrile seizure onset or age at study added significantly to the result. In a multiple regression, duration but not age had a significant effect on ipsilateral HF volume (figure 4). To help correct duration for the effect of age, we examined the relation of the ratio duration/age to HF volume. This variable had a significant effect on ipsilateral volume (R2 = 0.144, p < 0.03) and the ipsilateral/contralateral ratio (R2 = 0.183, p < 0.01), which was still present when FS were added to the regression. Among the patients with a history of complex FS, neither reported length nor latency to onset of afebrile seizures was correlated with HF volume.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 1. There is a significant decrease in hipocampal formation volume ipsilateral to the EEG focus with increasing duration of the seizure disorder (y = 3.203 − 0.023x; F = 6.66; p < 0.02).

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 2. Increasing duration of the seizure disorder is still associated with reduced hippocampal formation volume ipsilateral to the EEG focus even if patients with a history of complex or prolonged febrile seizures are excluded (y = 3.328 − 0.022x; F = 6.018; p < 0.03).

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 3. Increasing patient age did not have a significant effect on hippocampal formation volume ipsilateral to the epileptic focus (y = 3.191 − 0.013x; F = 1.335; p > 0.25).

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 4. Multiple regression plot of the interaction of the effect of age (x-axis) and duration (y-axis) on hippocampal formation (HF) volume ipsilateral to the epileptic focus (z-axis). Individual data points are shown. The smoother plane tilts down with increasing epilepsy duration and decreasing HF volume, but not with decreasing HF volume and increasing age (z = 2.81 + 0.023x − 0.04y; F = 4.242; p < 0.03).

Discussion.

Our study suggests that although patients with prolonged or complex FS are more likely to have HF volume loss, epilepsy duration has an additional effect. There is still a significant difference between the HF volume ipsilateral and contralateral to the epileptic focus in patients with no history of FS. Interestingly, the HF ipsilateral to the focus in FS− patients had the same volume as the contralateral HF in FS+ patients. There was a trend toward bilateral HF atrophy in the FS+ but not FS− patients, suggesting the effect of an early global insult. However, increasing epilepsy duration was inversely associated with ipsilateral but not contralateral HF volume, suggesting that any deleterious effect of persistent seizures is confined to the epileptogenic zone itself.

Other factors such as antiepileptic drug (AED) toxicity may play a role in the development of progressive HF atrophy. However, this effect would more likely be bilateral than more pronounced in the epileptic focus.

Several lines of evidence suggest that progressive damage may occur in epileptogenic zones in patients with TLE. The latent period frequently observed before seizure onset after an initial injury suggests an ongoing pathophysiologic process.13 Data from animal models show that in the dentate gyrus, a number of insults, including prolonged FS, head trauma, or encephalitis, may deafferent inhibitory neurons, disinhibiting the granule cell layer, leading to synchronous multilamellar discharges in response to cortical stimuli. Repetitive seizures may then lead to more extensive hippocampal damage.14 In rat dentate gyrus kindling models, intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons.15 In a kainic acid model of hippocampal sclerosis in the rat, mossy fiber sprouting increases progressively with longer survival after the lesion is created, suggesting an ongoing process.16 Moreover, an animal analogue of HF sclerosis can be induced by repeated kindled seizures in the rat. Cavazos et al.17 found that dentate gyrus and CA1 neuronal loss increased progressively with increasing seizure number, while other HF regions gradually became affected as well. No changes occurred in somatosensory cortex.

Human pathologic studies have also suggested increased damage with prolonged epilepsy duration.1,2 Babb et al.18 did not find an association with duration, but believed that this was due to the young age of most of their patients. Neuronal loss in CA1 and the prosubiculum in temporal lobe specimens resected at surgery was greater in patients who had had seizures for more than 20 years than it was in those with a shorter history.19 Patients with an “early risk factor” were reported to have lower hilar and granule cell densities in resected HF than were those without early risk.20 However, the patients also had longer epilepsy duration. HF cell loss may accompany extra-mesial temporal lesions, including gliomas, hamartomas, and heterotopias.21,22 Levesque et al.23 reported that heterotopias were associated with the most severe cell loss and that there was no relation to a history of febrile convulsions. These findings suggest that persistent seizures can lead to HF damage.

Progressive functional impairment in temporal lobe epileptogenic zones is supported by PET studies. We found a global reduction in glucose metabolism (CMRglc) related to epilepsy duration, but could not exclude the effects of age or other factors such as AEDs.24,25 Subsequent PET studies have shown an uncoupling between blood flow (CBF) and CMRglc in temporal lobe epileptic foci, with greater relative impairment of CMRglc.26,27 Moreover, the difference between the two measures increases with epilepsy duration, even though both appear to decline.28 The widening of the CBF–CMRglc mismatch was not related to a history of FS, onset age, or age at scan. AEDs, which have global effects on metabolism, are unlikely to be responsible for the process. Preliminary PET CMRglc data from a prospective study of children with new-onset seizures showed longer epilepsy duration in patients with hypometabolism.29

Previous vMRI studies of the relation of HF pathology to epilepsy duration have been contradictory. Spencer et al.4 reported that patients with mesial temporal seizure onset and HF atrophy on vMRI had significantly longer epilepsy duration than did those who had mesial temporal electrographic seizure onset but no atrophy, although age may not have been controlled for. Cendes et al.10 found that a history of FS, but not epilepsy duration, affected HF volume. Age at seizure onset was greater and epilepsy duration shorter than they were in our study. A preliminary study of newly diagnosed patients who had repeat MRIs after 1 year suggested that hippocampal sclerosis was found on a second study in several patients with normal initial scans.30 In a recent MRI study of children aged 8 to 33 months, VanLandingham et al.31 showed that prolonged or focal complex FS could be associated with acute HF injury. Progressive HF atrophy has been reported after status epilepticus both with and without persistent seizures, even when acute increases in T2 signal resolved.32,33 Fernandez et al.34 reported two families in which hippocampal malformations may have facilitated febrile convulsions and contributed to later epilepsy. Interestingly, several subjects in the study reported by VanLandingham et al.31 had evidence for HF pathology antedating the FS.

However, a minority of patients with uncontrolled CPS and mesial temporal sclerosis (MTS) have a history of complex or prolonged FS, or initial nonfebrile status. Kälviäinen et al.35 found an association between estimated seizure number and HF volume loss; in their study, both epilepsy duration and seizure number were correlated with increased T2 relaxation time.

The effects of TLE on the brain may extend beyond the primary epileptogenic zone. HF volume in our patients was reduced contralateral as well as ipsilateral to the epileptic focus, perhaps because of the severity of their epilepsy. Cook et al.36 reported that HF atrophy was widespread in patients with secondary generalized seizures. Ashtari et al.37 reported that left HF volume was significantly reduced in patients with right-sided EEG foci, but the reduction in right HF volume in patients with left-sided foci was not significant. Marsh et al.38 reported bilateral reductions of temporal neocortex and frontoparietal volume, as well as increased ventricular size, in patients with unilateral MTS. In a previous study, we found thalamic atrophy ipsilateral to the focus.39 Bilateral damage is found frequently in pathologic studies; these patients tend to have long epilepsy duration and severe seizures.1,2 HF damage, initially triggered by FS or another early insult, could be progressive in patients with uncontrolled TLE.

  • Received June 29, 1998.
  • Accepted September 12, 1998.

References

  1. ↵
    Margerison JH, Corsellis JAN. Epilepsy and the temporal lobes. Brain 1966;89:499–530.
    OpenUrlFREE Full Text
  2. ↵
    Mouritzen Dam A. Epilepsy and neuron loss in the hippocampus. Epilepsia 1980;21:617–630.
    OpenUrlCrossRefPubMed
  3. ↵
    Jack CR, Sharbrough FW, Twomey CK, et al. Temporal lobe seizures : lateralization with MR volume measurements of the hippocampal formation. Radiology 1990;175:423–429.
    OpenUrlPubMed
  4. ↵
    Spencer SS, McCarthy G, Spencer DD. Diagnosis of medial temporal lobe seizure onset : relative specificity and sensitivity of quantitative MRI. Neurology 1993;43:2117–2124.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Jack CR, Sharbrough FW, Cascino GD, Hirschorn KA, O’Brien PC, Marsh WH. Magnetic resonance image-based hippocampal volumetry : correlation with outcome after temporal lobectomy. Ann Neurol 1992;31:138–146.
    OpenUrlCrossRefPubMed
  6. ↵
    Cascino GD, Jack CJ, Parisi JE, et al. Magnetic resonance imaging-based volume studies in temporal lobe epilepsy : pathological correlations. Ann Neurol 1991;30:31–36.
    OpenUrlCrossRefPubMed
  7. Lencz T, McCarthy G, Bronen RA, et al. Quantitative magnetic resonance imaging in temporal lobe epilepsy : relationship to neuropathology and neuropsychological function. Ann Neurol 1992;31:629–637.
    OpenUrlCrossRefPubMed
  8. Loring DO, Mucro AM, Meador KJ, et al. Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy. Neurology 1993;43:1789–1793.
    OpenUrlAbstract/FREE Full Text
  9. ↵
    Trenerry MR, Jack CR, Sharbrough FW, et al. Quantitative MRI hippocampal volumes : association with onset and duration of epilepsy, and febrile convulsions in temporal lobectomy patients. Epilepsy Res 1993;15:247–252.
    OpenUrlCrossRefPubMed
  10. ↵
    Cendes F, Andermann F, Gloor P, et al. Atrophy of mesial structures in patients with temporal lobe epilepsy : cause or consequence of repeated seizures? Ann Neurol 1993;34:795–801.
    OpenUrlCrossRefPubMed
  11. ↵
    Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med 1976;295:1029–1033.
    OpenUrlCrossRefPubMed
  12. ↵
    Bhatia S, Bookheimer SY, Gaillard WD, Theodore WH. Measurement of whole temporal lobe and hippocampus for MR volumetry : normative data. Neurology 1993;43:2006–2011.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Goldensohn ES. The relevance of secondary epileptogenesis to the treatment of epilepsy : kindling and the mirror focus. Epilepsia 1984;25 (suppl 2):S156–S173.
  14. ↵
    Sloviter RS. The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy. Ann Neurol 1994;35:640–654.
    OpenUrlCrossRefPubMed
  15. ↵
    Bengzon J, Kokaia Z, Elmer E, Nanobashvili A, Kokaia M, Lindvall O. Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures. Proc Natl Acad Sci USA 1997;94:10432–10437.
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Yeoman KM, Mathern GW. Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainate in developing rats. Epilepsy Res 1996;26:219–231.
    OpenUrlCrossRefPubMed
  17. ↵
    Cavazos JE, Das I, Sutula TP. Neuronal loss induced in limbic pathways by kindling : evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci 1994;14:3106–3121.
    OpenUrlAbstract
  18. ↵
    Babb TL, Brown WJ, Pretorius J, Davenport C, Leib JP, Crandall PH. Temporal lobe volumetric cell densities in temporal lobe epilepsy. Epilepsia 1984;25:729–740.
    OpenUrlCrossRefPubMed
  19. ↵
    Mathern GW, Babb TL, Leite JP, Pretorius K, Yeoman KM, Kuhlman PA. The pathogenic and progressive features of chronic human hippocampal epilepsy. Epilepsy Res 1996;26:151–161.
    OpenUrlCrossRefPubMed
  20. ↵
    O’Connor W, Masukawa L, Freese A, Sperling MR, French JA, O’Connor MJ. Hippocampal cell distributions in temporal lobe epilepsy : a comparison between patients with and without an early risk factor. Epilepsia 1996;37:440–449.
    OpenUrlCrossRefPubMed
  21. ↵
    Babb TL, Brown WJ. Pathological findings in epilepsy. In: Engel J Jr, ed. Surgical treatment of the epilepsies. New York:Raven Press, 1987:511–540.
  22. ↵
    Drake J, Hoffman HJ, Kobayashi J, Hwang P, Becker LE. Surgical management of children with temporal lobe epilepsy and mass lesions. Neurosurgery 1987;21:792–797.
    OpenUrlPubMed
  23. ↵
    Levesque MF, Nakasato N, Vinters HV, Babb TL. Surgical treatment of limbic epilepsy associated with extrahippocampal lesions : the problem of dual pathology. J Neurosurg 1991;75:364–370.
    OpenUrlPubMed
  24. ↵
    Theodore WH, Fishbein D, Dubinsky R. Patterns of cerebral glucose metabolism in patients with partial seizures. Neurology 1988;38:1201–1206.
    OpenUrlAbstract/FREE Full Text
  25. ↵
    Lebrun-Grandie P, Baron JC, Soussaline F, Loch’h C, Sastre J, Bousser MG. Coupling between regional blood flow and oxygen utilization in the normal human brain. Arch Neurol 1983;40:230–236.
    OpenUrlCrossRefPubMed
  26. ↵
    Gaillard WD, Fazilat S, White S, et al. Interictal metabolism and blood flow are uncoupled in temporal lobe cortex of patients with partial epilepsy. Neurology 1995;45:1841–1848.
    OpenUrlAbstract/FREE Full Text
  27. ↵
    Fink GR, Pawlik G, Stefan H, Pietrzyk U, Wienhard K, Heiss WD. Temporal-lobe epilepsy : evidence for interictal uncoupling of blood flow and glucose-metabolism in temporomesial structures. J Neurol Sci 1996;137:28–34.
    OpenUrlCrossRefPubMed
  28. ↵
    Breier JI, Mullani NA, Thomas AB, et al. Effects of duration of epilepsy on the uncoupling of metabolism and blood flow in complex partial seizures. Neurology 1997;48:1047–1053.
    OpenUrlAbstract/FREE Full Text
  29. ↵
    Gaillard WD, Weinstein S, Conry J, et al. Regional FDG-PET hypometabolism is related to duration of partial epilepsy. Epilepsia 1996;37 (suppl 5):199. Abstract.
    OpenUrl
  30. ↵
    Van Paesschen W, Duncan JS, Connelly A. Progression of hippocampal disease in newly diagnosed localization-related epilepsy : a longitudinal quantitative MRI study. Epilepsia 1996;37 (suppl 5):190. Abstract.
    OpenUrl
  31. ↵
    VanLandingham KE, Heinz ER, Cavazos JE, Lewis DV. Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions. Ann Neurol 1998;43:413–426.
    OpenUrlCrossRefPubMed
  32. ↵
    Nohria V, Lee N, Tien RD, et al. Magnetic resonance imaging evidence of hippocampal sclerosis in progression : a case report. Epilepsia 1994;35:1332–1336.
    OpenUrlCrossRefPubMed
  33. ↵
    Wieshmann UC, Woermann FG, Lemieux L, et al. Development of hippocampal atrophy : a serial magnetic resonance imaging study in a patient who developed epilepsy after generalized status epilepticus. Epilepsia 1997;38:1238–1241.
    OpenUrlCrossRefPubMed
  34. ↵
    Fernández G, Effenberger O, Vinz B, et al. Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology 1998;50:909–917.
    OpenUrlAbstract/FREE Full Text
  35. ↵
    Kälviäinen R, Salmenperä T, Partanen K, Vainio P, Riekkinen P, Pitkänen A. Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy. Neurology 1998;50:1377–1382.
    OpenUrlAbstract/FREE Full Text
  36. ↵
    Cook MJ, Fish DR, Shorvon SD, Straughan K, Stevens JM. Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy. Brain 1992;115:1001–1015.
    OpenUrlAbstract/FREE Full Text
  37. ↵
    Ashtari M, Barr WB, Schaul N, Bogerts B. Three-dimensional fast low-angle shot imaging and computerized volume measurement of the hippocampus in patients with chronic epilepsy of the temporal lobe. AJNR 1991;12:941–947.
    OpenUrlAbstract/FREE Full Text
  38. ↵
    Marsh L, Morrell MJ, Shear PK, et al. Cortical and hippocampal volume deficits in temporal lobe epilepsy. Epilepsia 1997;38:576–587.
    OpenUrlCrossRefPubMed
  39. ↵
    DeCarli C, Hatta J, Fazilat S, Gaillard WD, Theodore WH. Extratemporal atrophy in patients with complex partial seizures of left temporal origin. Ann Neurol 1998;43:41–45.
    OpenUrlCrossRefPubMed

Disputes & Debates: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Methods.
    • Results.
    • Discussion.
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 99 (6)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • Neurology: Education
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2022 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise