Neuroimaging Evidence Of Progressive Neuronal Loss And Dysfunction In Temporal Lobe Epilepsy

Whether temporal lobe epilepsy is the result of an isolated, early injury or whether there is ongoing neuronal dysfunction or loss due to seizures is often debated. We attempt to address this issue by using magnetic resonance techniques. Proton magnetic resonance spectroscopic imaging can detect and quantify focal neuronal dysfunction or loss based on reduced signals from the neuronal marker N-acetylaspartate (NAA), and magnetic resonance imaging (MRI)-based measurements of hippocampal volumes (MRIvol) can quantify the amount of atrophy in this structure. We performed magnetic resonance spectroscopic imaging and MRIvol in 82 consecutive patients with medically intractable temporal lobe epilepsy to determine whether there was a correlation between seizure frequency, or type or duration of epilepsy, with NAA to creatine (Cr) values or hippocampal volumes. Volumes and spectroscopic resonance intensities were categorized as to whether they were measured from the temporal lobe ipsilateral or contralateral to the predominant electroencephalographic focus. Ipsilateral and contralateral NAA/Cr was negatively correlated with duration of epilepsy. Hippocampal volumes were negatively correlated with duration ipsilaterally but not contralaterally. Frequency of complex partial seizures was not correlated with any of the magnetic resonance measures. However, patients with frequent generalized tonic-clonic seizures had lower NAA/Cr bilaterally and smaller hippocampal volumes ipsilaterally than patients with none or rare generalized tonic- clonic seizures. The results suggest that although an early, fixed injury may cause asymmetric temporal lobe damage, generalized seizures may also cause progressive neuronal dysfunction or loss.455568576Margerison, J.H., Corsellis, J.A.N., Epilepsy and the temporal lobes: A clinical electroencephalographic and neuropathological study of the brain with particular reference to the temporal lobes (1966) Brain, 89, pp. 499-530Mathieson, G., Pathology of temporal lobe foci (1975) Advances in Neurology, 11, pp. 163-185. , Penry JK, Daly DD, eds. New York: Raven PressMeencke, H.J., Veith, G., Hippocampal sclerosis in epilepsy (1991) Epilepsy Surgery, pp. 705-715. , Luders HO, ed. New York: Raven PressBabb, T.L., Brown, W.J., Pathological findings in epilepsy (1987) Surgical Treatment of the Epilepsies, pp. 511-540. , Engel J, ed. New York: Raven PressDe Lanerolle, N.C., Kim, J.H., Robins, R.J., Spencer, D.D., Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy (1989) Brain Res, 495, pp. 387-395Gloor, P., Mesial temporal sclerosis: Historical background and an overview from a modern perspective (1991) Epilepsy Surgery, pp. 689-703. , Luders H, ed. New York: Raven PressKuzniecky, R.I., De La Sayette, V., Ethier, R., Magnetic resonance imaging in temporal lobe epilepsy: Pathological correlation (1987) Ann Neurol, 22, pp. 341-347Meyer, A., Falconer, M.A., Beck, E., Pathological findings in temporal lobe epilepsy (1954) J Neurol Neurosurg Psychiatry, 17, pp. 276-285Zimmerman, H.M., The histopathology of convulsive disorders in children (1940) J Pediatr, 13, pp. 359-390Ounsted, C., Lindsay, J., Norman, R., (1966) Biological Factors in Temporal Lobe Epilepsy, , London: William Heinemann Medical BooksCendes, F., Andermann, F., Dubeau, F., Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: An MRI volumetric study (1993) Neurology, 43, pp. 1083-1087Falconer, M.A., Serafetinides, E.A., Corsellis, J.A.N., Etiology and pathogenesis of temporal lobe epilepsy (1964) Arch Neurol, 10, pp. 233-248Harvey, A.S., Grattan-Smith, J.D., Desmond, P.M., Febrile seizures and hippocampal sclerosis: Frequent and related findings in intractable temporal lobe epilepsy of childhood (1995) Pediatr Neurol, 12, pp. 201-206Kuks, J.B., Cook, M.J., Fish, D.R., Hippocampal sclerosis in epilepsy and childhood febrile seizures (1993) Lancet, 342, pp. 1391-1394. , CommentMathern, G.W., Pretorius, J.K., Babb, T.L., Influence of the type of initial precipitating injury and at what age it occurs on course and outcome in patients with temporal lobe seizures (1995) J Neurosurg, 82, pp. 220-227Hauser, W.A., Status epilepticus: Frequency, etiology, and neurological sequelae (1988) Adv Neurol, 34, pp. 3-14Meldrum, B.S., Brierley, J.B., Prolonged epileptic seizures in primates: Ischemic cell change and its relation to ictal physiological events (1973) Arch Neurol, 28, pp. 10-17Shorvon, S., Neurophysiology, neuropathology and neurochemistry of status epilepticus (1994) Status Epilepticus, pp. 139-174. , Cambridge: Cambridge University PressCavazos, J.E., Indranil, D., Sutula, T.P., Neuronal loss induced in limbic pathways by kindling: Evidence for induction of hippocampal sclerosis by repeated brief seizures (1994) J Neurosci, 14, pp. 3106-3121Cavazos, J.E., Sutula, T.P., Progressive neuronal loss induced by kindling: A possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis (1991) Brain Res, 541, p. 179. , published erratum appears in(1990) Brain Res, 527, pp. 1-6Liu, Z., Nagao, T., Desjardins, G.C., Quantitative evaluation of neuronal loss in the dorsal hippocampus in rats with long-term pilocarpine seizures (1994) Epilepsy Res, 17, pp. 237-247Mouritzan-Dan, A.M., Hippocampal neuron loss in epilepsy and after experimental seizures (1982) Acta Neurol Scand, 66, pp. 601-642Mathern, G.W., Babb, T.L., Leite, J.P., The pathogenic and progressive features of chronic human hippocampal epilepsy (1996) Epilepsy Res, 26, pp. 151-161Mathern, G.W., Babb, T.L., Vickrey, B.G., The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy (1995) Brain, 118 (PART 1), pp. 105-118Cendes, F., Caramanos, Z., Andermann, F., Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: A series of 100 patients (1997) Ann Neurol, 42, pp. 737-746Cendes, F., Andermann, F., Dubeau, F., Arnold, D.L., Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy (1995) Magn Reson Imaging, 13, pp. 1187-1191Cendes, F., Andermann, F., Gloor, P., MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy (1993) Neurology, 43, pp. 719-725Luby, M., Spencer, D.D., Kim, J.H., Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy (1995) Magn Reson Imaging, 13, pp. 1065-1071Jackson, G.D., Kuzniecky, R.I., Cascino, G.D., Hippocampal sclerosis without detectable hippocampal atrophy (1994) Neurology, 44, pp. 42-46Nohria, V., Lee, N., Tien, R.D., Magnetic resonance imaging evidence of hippocampal sclerosis in progression: A case report (1994) Epilepsia, 35, pp. 1332-1336Saukkonen, A., Kalviainen, R., Partanen, K., Do seizures cause neuronal damage? A MRI study in newly diagnosed and chronic epilepsy (1994) Neuroreport, 6, pp. 219-223Trenerry, M.R., Jack C.R., Jr., Sharbrough, F.W., Quantitative MRI hippocampal volumes: Association with onset and duration of epilepsy, and febrile convulsions in temporal lobectomy patients (1993) Epilepsy Res, 15, pp. 247-252Salmenpera, T., Kalviainen, R., Partanen, K., Pitkanen, A., Hippocampal damage caused by seizures in temporal lobe epilepsy (1998) Lancet, 351, p. 35. , LetterVermathen, P., Ende, G., Laxer, K.D., Hippocampal N-acetylaspartate in neocortical epilepsy and mensial temporal lobe epilepsy (1997) Ann Neurol, 42, pp. 194-1995Moffett, J.R., Namboodiri, M.A., Cangro, C.B., Neale, J.H., Immunohistochemical localization of N-acetylaspartate in rat brain (1991) Neuroreport, 2, pp. 131-134Simmons, M.L., Frondoza, C.G., Coyle, J.T., Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies (1991) Neuroscience, 45, pp. 37-45Cross, J.H., Connelly, A., Jackson, G.D., Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy (1996) Ann Neurol, 39, pp. 107-113Ng, T.C., Comair, Y.G., Xue, M., Temporal lobe epilepsy: Presurgical localization with proton chemical shift imaging (1994) Radiology, 193, pp. 465-472Cendes, F., Andermann, F., Preul, M.C., Arnold, D.L., Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images (1994) Ann Neurol, 35, pp. 211-216Kuzniecky, R., Hugg, J.W., Hetherington, H., 1H MRS imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy (1998) Neurology, 51, pp. 66-71Garcia, P.A., Laxer, K.D., Van Der Grond, J., Correlation of seizure frequency with N-acetyl-aspartate levels determined by 1H magnetic resonance spectroscopic imaging (1997) Magn Reson Imaging, 15, pp. 475-478Roth, K., Kimber, B.J., Feeny, J., Data shift accumulation techniques for overcoming dynamic range problems (1980) J Magn Reson, 41, pp. 302-309Connelly, A., Jackson, G.D., Duncan, J.S., Magnetic resonance spectroscopy in temporal lobe epilepsy (1994) Neurology, 44, pp. 1411-1417Hetherington, H., Kuzniecky, R., Pan, J., Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T (1995) Ann Neurol, 38, pp. 396-404Petroff, O.A., Pleban, L.A., Spencer, D.D., Symbiosis between in vivo and in vitro NMR spectroscopy: The creatine, N-acetyl-aspartate, glutamate, and GABA content of the epileptic human brain (1995) Magn Reson Imaging, 13, pp. 1197-1211Hugg, J.W., Laxer, K.D., Matson, G.B., Neuron loss localizes human temporal lobe epilepsy by in vivo proton magnetic resonance spectroscopic imaging (1993) Ann Neurol, 34, pp. 788-794Mathews, P.M., Andermann, F., Arnold, D.L., A proton magnetic resonance spectroscopy study of focal epilepsy in human (1990) Neurology, 40, pp. 985-989Petroff, O.A., Spencer, D.D., Alger, J.R., Prichard, J.W., High-field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy (1989) Neurology, 39, pp. 1197-1202Watson, C., Andermann, F., Gloor, P., Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging (1992) Neurology, 42, pp. 1743-1750Mouritzan-Dan, A.M., Epilepsy and neuron loss in the hippocampus (1980) Epilepsia, 21, pp. 617-629Davies, K.G., Hermann, B.P., Dohan F.C., Jr., Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients (1996) Epilepsy Res, 24, pp. 119-126Harvey, A.S., Berkovic, S.F., Wrennall, J.A., Hopkins, I.J., Temporal lobe epilepsy in childhood: Clinical, EEG, and neuroimaging findings and syndrome classification in a cohort with new-onset seizures (1997) Neurology, 49, pp. 960-968Golomb, J., De Leon, M.J., Kluger, A., Hippocampal atrophy in normal aging. An association with recent memory impairment (1993) Arch Neurol, 50, pp. 967-973Cendes, F., Andermann, F., Dubeau, F., Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy. Evidence from proton MR spectroscopic imaging (1997) Neurology, 49, pp. 1525-1533Hugg, J.W., Kuzniecky, R.I., Gilliam, F.G., Normalization of contralateral metabolic function following temporal lobectomy demonstrated by 1H magnetic resonance spectroscopic imaging (1996) Ann Neurol, 40, pp. 236-239Mani, R.B., Lohr, J.B., Jeste, D.V., Hippocampal pyramidal cells and aging in the human: A quantitative study of neuronal loss in sectors CA1 to CA4 (1986) Exp Neurol, 94, pp. 29-40Mouritzan-Dan, A.M., The number of hippocampal neurons in rats after electrically-induced seizures (1980) Brain Res, 193, pp. 268-272Mathern, G.W., Leite, J.P., Pretorius, J.K., Children with severe epilepsy: Evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation (1994) Brain Res, 78, pp. 70-8