Differential neuronal and glial relations with parameters of ictal discharge in mesial temporal lobe epilepsy.

PURPOSE: EEG recordings of spontaneous seizures should provide clues to epilepsy pathogenesis and pathology. We examined onset, propagation, and termination characteristics of spontaneous seizures recorded by intracranial EEG in temporal lobe (TL) epilepsy in relation to neuronal, glial, and synaptic changes in the same tissue. METHODS: All of our patients with intracranial EEG recordings of spontaneous TL seizure onset, subsequent TL resection, and quantitative pathologic analysis of resected tissue were included. Seizure parameters were mean time to initial propagation, mean total electrical duration, uniformity of seizure-onset distribution and location, and percentage of seizures with spiking onset per patient. Tissue was analyzed for glial and neuronal density in hippocampal fields and presence of sprouting. Outcome was classified as seizure free or not. RESULTS: All seizures with onset in resected TL in 62 patients were analyzed. The percentage of each patient's seizures with spike onsets was significantly correlated with glial density in CA3 (p < 0.01). Initial propagation time was significantly and inversely correlated with neuronal density in CA4 (p < 0.02). Electrical seizure duration was significantly correlated with glial density in CA2 and CA3 (p < 0.02). Neuronal and glial density were significantly (and inversely) related to one another only in CAI (p < 0.001). Outcome was most significantly related to uniform hippocampal seizure onset. Presence or absence of sprouting was not significantly related to outcome or any EEG measure. CONCLUSIONS: These results suggest both glia and neurons exert independent influences on the expression of ictal discharges in seizures of medial TL onset. Glial density influenced interictal-ictal transition, whereas neuronal density influenced seizure propagation. These findings may have implications for pathogenesis.

Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy.

Forty-nine consecutive patients undergoing anteromedial temporal lobe resection for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo to 4 yr) postoperative follow-up, were selected for a retrospective study. This study correlated magnetic resonance imaging (MRI) derived hippocampal volumetrics, preoperative demographics, postoperative seizure control, and tissue analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell counts, and immunohistochemistry (IHC) evidence for dentate sprouting and reorganization. These measures were compared in hippocampi with or without an adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis (MTS) was defined as > 50% neuronal cell loss averaged across all CA fields with NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may not include granule cell sprouting as determined by dynorphin staining. Patients were divided into two groups based on CA field neuronal cell counts, one averaging > 50% cell loss and one averaging < 50% cell loss. For the MTS group (N = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74% had dentate reorganization, and complete seizure control was seen in 76% of these patients. In one subgroup of the < 50% cell loss group, patients with medial temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group) (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely controlled in 67%. For the second subgroup of the < 50% cell loss group, patients without mass lesions (N = 5) who were classified as the paradoxical medial temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal atrophy, 0% had dentate reorganization, and complete seizure control was seen in 60% of these patients. In conclusion, for the MTS group, hippocampal atrophy proven by MRI volumetrics was highly predictive of significant neuronal cell loss and an excellent indicator of success. However, in patients who had a foreign mass, hippocampal atrophy was not necessarily indicative of significant neuronal cell loss and MRI volumetrics was not a factor in the determination of a successful outcome. Furthermore, patients without mass lesions who have normal volumetrics but demonstrate hippocampal disease through invasive electrode monitoring, are likely to have paradoxical medial temporal lobe epilepsy, seizures beginning at a later age, and a lower, but not insignificant, success rate than the classical mesial temporal sclerosis group.

Ultrastructural analysis of axosomatic contacts on functionally identified primate spinothalamic tract neurons.

The morphology and frequency of axosomatic contacts on three functionally identified primate spinothalamic tract (STT) cells were analyzed at the electron microscopic level. The STT cells analyzed were wide-dynamic-range neurons responsive to activation of low- and high-threshold cutaneous afferents innervating the foot. The somas were located in the lateral border of lamina V; the dendritic trees were oriented dorsally and were very extensive. Numerous spinelike appendages were observed emanating from two of the cell bodies. Terminal types contacting the cell bodies were categorized at several different layers through each neuron. Six morphologically different terminal types were established following analysis of serial sections. Profiles classified as round (R) terminals containing round clear vesicles and zero or one dense-core vesicle made up over 50% of the total population in contact with the STT somas. Profiles containing round clear vesicles and two to four small-diameter dense-core vesicles (D1 category) made up approximately 10% of the population in contact with each soma. Flat (F) terminals with oblong or flattened clear vesicles made up approximately 8% of the population. The remaining three categories (D2, L1, and L2) distinguished by the number and size of the dense-core vesicles made up a small percentage of the total population in contact with the cell bodies. The distribution of terminal types on the soma proper versus somatic spines was also determined for one cell. The proportions of the six terminal types contacting the soma of these cells were very similar, although the physiological characteristics of each cell were different. However, the relative proportions of terminal types on these three lamina V STT cell bodies were different from those previously reported contacting somata in lamina V, suggesting that there may be a unique innervation of STT cells that differentiates them from other cell types in lamina V.

Corticotroph cell pituitary adenoma within an ovarian teratoma. A new cause of Cushing's syndrome.

A 24-year-old woman with severe Cushing's syndrome was found to have corticotroph cell pituitary adenoma arising within a benign cystic ovarian teratoma. The patient manifested sustained hypercortisolemia and lack of suppression of either adrenocorticotropin (ACTH) or cortisol production. There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumor led to normalization of ACTH and cortisol levels. Densely granulated corticotroph tumor cells with prominent Type I microfilaments and intracytoplasmic ACTH immunoreactivity characterized the neoplasm as a pituitary corticotroph cell adenoma. This is, to our knowledge, the first case reported of a functioning pituitary adenoma arising within a benign cystic teratoma.

Avian archistriatal control of fear-motivated behavior and adrenocortical function.

Bilateral section of the efferent pathway (tractus occipitomesencephalicus) from the archistriatum of the duck depresses fear-motivated responses as measured by (a) latency to escape in a runway test; (b) latency to approach and drink in the experimenter's presence following water deprivation, and (c) number of agonistic responses directed to an object introduced into the home cage. Sectioning this pathway also raises plasma corticosteroid levels in both adult mallards and newly hatched chickens. Plasma corticosteroid levels were negatively correlated with latency to approach and drink in controls. Experimental reduction of the neutral output of the mallard archistriatum produces an animal that resembles the adult domesticated duck in its basal plasma corticosteroid level and in its avoidance behavior, suggesting that selection for reduced archistriatal activity occurs during domestication.