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Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy.

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mediated diaschisis might explain multiregional hypometabolism. W e tested the hypothesis that hippocampal neuronal loss correlates positively with interictal
hypornetablism of extrahippocampal areas in TLE.
Hippocampal Neuronal
Loss and Regional
HvDometabolism in
Timporal Lobe Epilepsy
Thomas R. Henry, MD," Thomas L. Babb, PhD,t
Jerome Engel, Jr, MD, PhD,t$
John C. Mazziotta, MD, PhD, ?§'I
Michael E. Phelps, PhD,§" and Paul H. Crandall, MDq
T h e pathophysiology of widespread interictal hypometabolism in temporal lobe epilepsy is unknown but
might reflect neuronal loss and diaschisis. We found no
significant correlation between any cortical region's metabolism on preoperative {'*F}fluorodeoxyglucose positron emission tomography and neuronal density of resected hippocampi in 40 patients. We conclude that
hippocampal neuronal loss and diaschisis cannot account
for the regional interictal hypometabolism of temporal
lobe epilepsy.
Henry TR, Babb TL, Engel J Jr, Mazziotta JC,
Phelps ME, Crandall PH. Hippocampal neuronal
loss and regional hypometabolism in temporal lobe
epilepsy. Ann Neurol 1774;36:725-927
Unilateral temporal lobe epilepsy (TIE) usually demonstrates widespread glucose hypometabolism of the
epileptogenic temporal lobe and ipsilateral extratemporal areas interictally [l-31. Hypometabolic patterns
imaged with ["Flfluorodeoxyglucose (FDG) positron
emission tomography (PET) are useful in presurgical
epilepsy evaluations {Z, 31, but the pathophysiology of
interictal hypometabolism remains tinclear.
Synaptic activity probably accounts for most regional
cerebral glucose consumption [4}. Loss of neurons and
their synapses by infarction o r other insults causes localized hypometabolism at the site of pathology and
sometimes also at uninsulted cerebral regions. Diaschisis can be defined to include all distant effects of regional insult { 5 ] , although von Monakow originally limited the phenomenon to areas receiving projections
from insulted regions [b].Hippocampal sclerosis (neuronal loss and gliosis) is the most common pathology in
surgically treated TLE 17, S] and with polysynaptically
From the "Department of Neurology, Emory University, Atlanta,
GA, a;nd the Departments of $Anatomy and Cell Biology, tNeurology, 'Neurosurgery, $Pharmacology, and "Radiological Sciences,
University of California, L a Angeles, CA.
Received Dec 1, 1993, and in revised form Jun 6, 1994. Accepted
for publication Jun 9, 1994.
Address correspondence to Dr Henry, Department of Neurology,
Emory University, Woodruff Memorial Research Building, Suite
6000, PO Drawer V, 1639 Pierce Drive, Atlanta, GA 30322.
Materials and M e t h o d s
Forty TLE patients were selected consecutively from UCLA
epilepsy surgeries using reported criteria [7] and exclusion
of foreign-tissue lesions suspected on preoperative neuroimaging or histologically detected. Temporal lobectomy was
on the right in 22 and left in 18 patients.
Preoperative PET was performed with 10 mCi FDG and
the NeuroECAT tomograph (CTI-Siemens). Procedures for
performing and analyzing FDG studies in patients and 10
normal volunteers (consenting with Institutional Review
Board approval) have been presented [7]. None reported
partial seizures with 24 hours or generalized seizures within 7
days before PET. None had seizures or postictal dysfunction
behaviorally or on electroencephalography (EEG) during
FDG uptake. We analyzed regional metabolism as absolute
metabolic rate, as a ratio of metabolism between contralateral
homologues (asymmetry index), and as a ratio between regional and global cerebral metabolism (bihemispheric index)
[7]. Similar ratios were calculated for each region's volume
(number of included image pixels). Table 1 lists hypometabolic regions by individual. None had hypometabolism contralateral to lobectomy in any analysis.
Neuronal losses in temporal lobe subregions were quantified as previously described [7). Neuronal counts for hippocampal subfields and prosubiculum were averaged into a
composite hippocampal measure. CA1 is the subfield most
likely to show neuronal loss in TLE 17,81, but widespread
loss of projection neurons is better represented by hippocampal densities. Individual CA1 and hippocampal data are listed
in Table 1. None had significant neuronal loss in temporal
neocortex.
Hippocampal and CA1 neuronal losses were independently correlated with metabolism of each PET region across
the 40 subjects with Pearson's coefficient. Bonferroni's
method corrected for effects of repeated measures. Volumes
of PET regions were substituted for metabolic rate in another
set of correlations with neuronal loss.
x2 or Fisher exact tests assessed relationships between regional metabolic patterns and neuronal loss. Normal versus
decreased metabolism of each region was compared with
greater- versus less-than-50% hippocampal neuronal loss, because 50% or greater loss defined hippocampal sclerosis [7}.
Another set of two-by-two tables was tested, with substitution of greater- versus less-than-70% hippocampal neuronal
loss, because this criterion divided the group more equally.
Two additional sets were tested, substituting CAI for hippocampal losses.
Results
No single region's metabolic rate was significantly correlated with hippocampal or CA1 neuronal loss at p <
0.05 in analyses using the bihemispheric metabolic index (see Table 2); a significant correlation coefficient
of 0.46 indicated a modest relationship between hippocampal neuronal loss and hypometabolism of the entire
Copyright 0 1974 by the American Neurological Association 925
Table 1. Regional Interictal Glucose Hypometabolism and Neuronal Losses in Temporal Lobe Epilepsy Patients
CNP#"
143
155
163
168
170
173
175
176
178
180
182
187
171
173
194
203
207
207
210
21 1
214
217
22 1
225
227
234
G3
OP13
X
XI1
XI11
xv
XVI
XVIII
xx
XXI
XXIII
xxv
XXVI
XXVIII
Hypometabolic
Regionsb
CA 1
Cell Lossc
Hippocampal
Cell Lossc
Antiepileptic
MT,-LT, Th
MT, LT, Th
MT
Th
97
100
66
-
34
80
60
33
63
70
87
83
67
86
82
18
70
53
81
72
54
30
71
CBZ, PHT
CBZ
CBZ, PHT
PB
CBZ, VPA
PB
CBZ
CBZ
PHT, PRM
CBZ
CBZ, PB
PHT
CBZ, CZP, PHT
CBZ
CBZ, PHT
VPA
CBZ, PHT
CBZ
CBZ
CBZ
CBZ, PHT
CBZ
CBZ
CBZ, PRM
CBZ, PHT
CBZ
CBZ, PHT
PHT
CBZ
CBZ, CZP, PHT
CBZ, PHT
PHT
CBZ, PHT
CBZ
PHT
CBZ, PHT, VPA
CBZ
CBZ, PHT, VPA
CBZ, PHT
CBZ, PRM
MT, LT, F, Th
MT, LT, P, BG, Th
MT, LT, P, Th
Th
MT, LT, F, P, BG, Th
MT, LT, BG, Th
MT, P, Th
-
LT, P, Th
MT
MT, LT, F, BG, Th
F, BG, Th
-
LT
MT, LT
MT, LT, F, P, 0, BG, Th
LT
MT, LT
-
MT, LT, F
MT, LT, Th
Th
73
71
44
75
80
90
73
75
95
21
80
80
97
77
87
51
83
77
82
70
80
89
73
-
-
LT, F, BG
MT, P, BG
MT, LT, Th
MT, LT, Th
MT, LT, F, Th
MT, Th
MT, LT, Th
MT, LT, Th
MT, LT, Th
MT, LT, Th
MT, LT, Th
77
70
30
77
70
70
73
94
88
65
90
77
74
57
64
73
73
78
45
87
74
37
40
66
76
51
73
77
84
60
Drugsd
"Patient identification numbers of the Clinical Neurophysiology Program (CNP) of the University of Caifornia at Los Angeles.
bHypometabolism is defined as an asymmetry index more than 2 SD from the normal mean value for that region. Asymmetry indices of
metabolism are presented here because they are more sensitive to regional hypometabolism in individual patients than are absolute metabolic
rates and bihemispheric indices of metabolism 191. In each case an abnormal index indicated lower metabolism on the epileptogenic side: Each
positron emission tomographic (PET) region extends across multiple imaging planes, as previously defined "91 (BG = basal ganglia; F =
frontal; LT = lateral temporal; MT = mesial temporal; 0 = occipital; P = parietal; Th = thalamic).
'Neuronal loss is the percent decrease below mean normal densities of the histologic subfield, as previously defined 171.
dThe antiepileptic drugs used chronically at the time of PET are abbreviated (CBZ = carbamazepine; CZP = clorazepate; PB = phenobarbital;
PHT = phenytoin; PRM = primidone; VPA = valproate).
926 Annals of Neurology Vol 36 N o 6 December 1774
Table 2. Pearson Correlations of Regional Metabolism Versus
Newonal Lossesa
Mesial temporal
Lateral temporal
Frontal
Parietal
Occipital
Basal ganglia
Thalamic
Hemispheric
CA 1
Hippocampus
- 0.02
-
0.31
0.2 1
- 0.2 1
-0.10
0.29
0.15
0.27
0.07
0.12
0.17
-0.16
- 0.08
0.25
0.22
0.46b
”The bihemispheric index of metabolism of each region is correlated
with neuronal losses in 40 subjects.
‘Significant arp < 0.05, following Bonferroni correction for multiple
comparisons.
hemisphere on the epileptogenic side. For absolute
metabolic rate and the asymmetry metabolic index,
correlation coefficients were slightly lower than those
in Table 2. No correlations were significant for left and
right TLE subgroups tested separately.
No PET region’s volume loss was significantly correlated with degree of CA1 or hippocampal neuronal
losses. This does not contradict a report that decreased
hippocampal magnetic resonance imaging (MRI) volume correlates well with severity of neuronal loss in
resected hippocampi [lo}, because our mesial temporal PET region includes the hippocampus and multiple
adjacent structures E91.
Hypometabolism of individual PET regions was not
significantly associated with greater CA 1 or hippocampal neuronal loss on x2 or Fisher exact testing. Regional
hypometabolism was not significantly associated with
carbamazepine (or phenytoin) monotherapy or carbamazepine (or phenytoin) absence at PET on Fisher exact testing.
Discussion
Our findings indicate that diaschisis associated with
hippocampal neuronal loss is, at most, a minor factor
in producing the widely distributed interictal hypometabolism of TLE.
An alternative hypothesis is that diaschisis associated
with hippocampal and additional extrahippocampal
neuronal losses might explain these metabolic patterns.
Temporal neocortex had no significant neuronal losses
in our patients, but we cannot assess unresected neuronal populations in vivo. Amygdalar neurons are lost
in some TLE patients Ell]. Qualitative estimation revealed thalamic and extratemporal neocortical neuronal losses in some autopsied TLE patients [12}. This
hypothesis might be tested with an as yet undeveloped
PET tracer and kinetic model for neuronal density.
Another hypothesis is that effects of seizures on glucose metabolism outlast the postictal period defined
by behavior and EEG, causing variability in “interictal”
regional metabolism. Such effects of seizures on regional metabolism might be detected with intrasubject
FDG PET comparisons at different intervals following
seizures, during periods of stable seizure frequency.
A third hypothesis is that interictal regional metabolism reflects synaptic density and that synaptic densities
in the hippocampus and other regions are altered, to
some extent, independently of neuronal density
changes. “Epileptic reorganization,” such as mossy fiber
sprouting in sclerotic hippocampi [131, could alter synaptic density independently of neuronal density in hippocampi and perhaps elsewhere. Stereological electron
microscopy { 141 could measure synaptic densities in
resected tissue to test this hypothesis.
This work was supported in part by National Institutes of Health
grants NS-02808 and NS-15654 and by Department of Energy contract DE-AC03-76-SF000112.
We thank James Pretorius, MS, for technical assistance in neuronal
quantification and Sally Mouilleseaux for assistance in the preparation of this manuscript.
References
1. Engel J Jr, Brown WJ, Kuhl DE, et al. Pathological findings
underlying focal temporal lobe hypometabolism in partial epilepsy. Ann Neurol 1982;12:518-528
2. Henry TR, Chugani HT, Abou-Khalil BW, et al. Positron emission tomography. In: Engel J Jr, ed. Surgical treatment of the
epilepsies. 2nd ed. New York: Raven Press, 1993:211-232
3. Theodore WH, Sat0 S, Kufta C, et al. Temporal lobectomy for
uncontrolled seizures: the role of positron emission tomography. Ann Neurol 1992;32:789-794
4. Schwartz WJ, Smith CB, Davidsen L, et al. Metabolic mapping
of functional activity in the hypothalamo-neurohypophysial system of the rat. Science 1979;205:723-725
5. Meyer JS, Hata T, Imai A. Clinical and experimental studies of
diaschisis. In: Wood JH, ed. Cerebral blood flow. New York:
McGraw-Hill, 1987:481-502
6. Feeney DM, Baron J-C. Diaschisis. Stroke 1986;17:817-830
7. Babb TL, Brown WJ, Pretorius J, et al. Temporal lobe volumetric cell density in temporal lobe epilepsy. Epilepsia 1984;25:
729-740
8. Bruton CJ. The neuropathology of temporal lobe epilepsy. Oxford: Oxford University Press, 1988
9. Henry TR, Mazziotta JC, Engel J Jr, et al. Quantifying interictal
metabolic activity in human temporal lobe epilepsy. J Cereb
Blood Flow Metab 1990;10:748-757
10. Cascino GD, Jack CR, Parisi JE, et al. Magnetic resonance
imaging-based volume studies in temporal lobe epilepsy: pathological correlations. Ann Neurol 1991;3031-37
11. Hudson LP, Munoz DG, Miller L, er al. Amygdaloid sclerosis
in temporal lobe epilepsy. Ann Neurol 1993;33:622-63 1
12. Margerison JH, Corsellis JAN. Epilepsy and the temporal lobes:
a clinical, electroencephalographic and neuropathological study
of the brain in epilepsy, with special reference to the temporal
lobes. Brain 1966;89:499-530
13. Sutula T, Cascino G, Cavazos J, et al. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol
1989;26:3 2 1-3 30
14. Calverly RKS, Jones DG. Determination of numerical density
of perforated and nonperforated synapses. In: Conn PM, ed.
Methods in the neurosciences, vol 3: quantitative and qualitative
microscopy. San Diego: Academic Press, 1990:155-172
Brief Communication: Henry et al: Neuronal Loss and Metabolism 927
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