Faculty Bibliography

Biogenic amines in well defined subtypes of human temporal lobe epilepsy (TLE) have not been well characterized. Specimens from five patients with neocortical TLE (NTLE) and nine with mesial TLE (MTLE) were immediately placed in Ringer's lactate; stearate indicator microelectrodes were placed in temporal gray matter, Ag/AgCl reference microelectrodes and auxiliary microelectrodes were placed 3-7 mm contralaterally to the indicator microelectrode. Dopamine (DA), ascorbic acid (AA), norepinephrine (NE) and serotonin (5-HT) were identified by their characteristic oxidative potentials in vitro. Four of five patients with NTLE had NE depletion in temporal neocortex while eight of nine patients with MTLE had high concentrations of NE (chi-square P<0.01). Significant concentrations of DA were present in the temporal lobes of three of five NTLE patients but in only one of the nine MTLE patients (chi-square P<0.05). 5-HT was present in the neocortex of both NTLE and MTLE patients in similar concentrations. AA was found in the neocortex of one NTLE patient. These data support an association between NE depletion and NTLE. The relative NE deficiency along with the consistent presence of DA in NTLE patients suggest an impairment in the catecholamine pathway. The presence of AA, a co-factor in NE synthesis, in the neocortex of one NTLE patient may also be related since AA is a cofactor in NE synthesis

It is known that epilepsy patients diagnosed with neocortical temporal lobe epilepsy (NTLE), differ from those diagnosed with mesial temporal lobe epilepsy (MTLE), e.g., in hippocampal (HPC) pathology. In the present studies, we tested the hypothesis that NTLE and MTLE subtypes of human epilepsy might differ in regards to their HPC monoamine neurochemistry. Monoamine neurotransmitters were studied in separate signals and within s with semiderivative microvoltammetry, used in combination with stearate indicator, Ag-AgCl reference and stainless steel auxiliary microelectrodes. Anterior HPC specimens from the patients' epileptogenic zone, defined by electrocorticography, were resected neurosurgically from 13 consecutive patients with intractable temporal lobe epilepsy. Four patients were diagnosed with NTLE and nine with MTLE. The criteria for the diagnosis of NTLE versus MTLE was absence versus presence of HPC sclerosis, respectively, based on MRI examination of resected tissue. In addition, NTLE patients demonstrated seizure onset in anterolateral temporal neocortex on electroencephalography (EEG). HPC subparcellations studied were: (a) Granular Cells of the Dentate Gyrus (DG), (b) Polymorphic Layer of DG and (c) Pyramidal Layer: subfields, CA1 and CA2. Dopamine (DA), serotonin (5-HT), norepinephrine (NE) and ascorbic acid (AA) (co-factor in DA to NE synthesis), exhibited separate and characteristic half-wave potentials in millivolts. Each half-wave potential, i.e., the potential at which maximum current was generated, was experimentally established in vitro. Concentrations of neurotransmitters found in HPC subparcellations were interpolated from calibration curves derived in vitro from electrochemical detection of monoamines and AA in saline phosphate buffer. Significant differences between subtypes in concentration of monoamines were analyzed by the Mann Whitney rank sum test and those differences in probability distribution of monoamines were analyzed by the Fisher Exact test; in each case, P<0.01 was the criteria selected for determining statistical significance. DA concentrations were higher in NTLE compared with MTLE in each HPC subparcellation [P=0.037, 0.024 and 0.007, respectively (P<0.01)] and DA occurred more frequently in NTLE in the Pyramidal Layer [P=0.077 (P<0.01)]. AA was present in one NTLE patient. NE concentrations were higher in MTLE vs. NTLE in each subparcellation [P=0.012, 0.067 and 0.07, respectively (P<0.01)] and NE occurred more frequently in MTLE in Granular Cells of DG and Pyramidal Layer [P=0.052 and 0.014, respectively (P<0.01)]. In MTLE, NE concentrations in the CA1 subfield of the Pyramidal Layer were decreased vs. the CA2 subfield [P=0.063 (P<0.01)]. Serotonin was found in every HPC subparcellation of each subtype but 5-HT concentrations were higher in NTLE vs. MTLE in the Granular Cells of DG and the Pyramidal Layer (CA1 subfield) [P=0.076 and 0.095, respectively (P<0.01)]. Thus, this preliminary study showed that marked differences in HPC monoamine neurochemistry occurred in NTLE patients as compared with MTLE patients

PURPOSE: To investigate the relation between the number and spatial distribution of language sites and specific patient-and epilepsy-related variables. METHODS: Patients with stimulation-induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function. RESULTS: Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full-scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory. CONCLUSIONS: Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills

The phosphorylation state of the proteins, regulated by phosphatases and kinases, plays an important role in signal transduction and long-term changes in neuronal excitability. In neurons, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and calcineurin (CN) are attached to a scaffold protein, A kinase anchoring protein (AKAP), thought to anchor these three enzymes to specific sites of action. However, the localization of AKAP, and the predicted sites of linked phosphatase and kinase activities, are still unknown at the fine structural level. In the present study, we investigated the distribution of AKAP79 in the hippocampus from postmortem human brains and lobectomy samples from patients with intractable epilepsy, using preembedding immunoperoxidase and immunogold histochemical methods. AKAP79 was found in the CA1, presubicular and subicular regions, mostly in pyramidal cell dendrites, whereas pyramidal cells in the CA3, CA2 regions and dentate granule cells were negative both in postmortem and in surgical samples. In some epileptic cases, the dentate molecular layer and hilar interneurons also became immunoreactive. At the subcellular level, AKAP79 immunoreactivity was present in postsynaptic profiles near, but not attached to, the postsynaptic density of asymmetrical (presumed excitatory) synapses. We conclude that the spatial selectivity for the action of certain kinases and phosphatases regulating various ligand- and voltage-gated channels may be ensured by the selective presence of their anchoring protein, AKAP79, at the majority of glutamatergic synapses in the CA1, but not in the CA2/CA3 regions, suggesting profound differences in signal transduction and long-term synaptic plasticity between these regions of the human hippocampus.

Right hemisphere functions were examined during cortical stimulation in six patients undergoing epilepsy surgery. Two patients showed mild hemispatial neglect and constructional disability with stimulation of several sites in the inferior parietal lobule and posterior temporal lobe. Two other patients showed no disruption of visuospatial functions with stimulation of similar parietal or posterior temporal sites. Nonverbal acoustic perception of environmental sounds was not disrupted with stimulation of right superior temporal cortex in one patient, and musical abilities were not affected by right superior temporal stimulation in another patient. Nondominant hemisphere functions may be more widely distributed and less localized than linguistic functions in the dominant hemisphere