William Feindel

Excitatory amino acids are elevated in human epileptic cerebral cortex

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)—epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)—temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (μmol/g protein, mean ±: SEM): glutamate—spiking 109.8 ±: 1.8, nonspiking 87.4 ±: 2.0 (p < 0.001); aspartate—spiking 15.2 ±: 0.9, nonspiking 12.2 ±: 0.5 (p < 0.05); GABA—spiking 15.0 ±: 1.0, nonspiking 13.9 ±: 1.4 (NS); taurine—spiking 14.5 ±: 0.8, nonspiking 12.2 ±: 0.8 (NS); and glycine—spiking 11.5 ±: 0.8, nonspiking 7.4 ±: 0.6 (p < 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.

Dynamic positron emission tomography for study of cerebral hemodynamics in a cross section of the head using positron-emitting 68Ga-EDTA and 77Kr.

Dynamic positron emission tomographic studies were performed on over 120 patients with occlusive cerebrovascular disease, arteriovenous malformations, and brain tumors, using the positron section scanner, consisting of a ring of 32 scintillation detectors. The radiopharmaceuticals were nondiffusible 68Ga-EDTA for transit time and uptake studies and the diffusible tracer, 77Kr, for quantitative regional cerebral blood flow studies in every square centimeter of the cross section of the head. The results of dynamic positron emission tomography in correlation with the results from the gamma scintillation camera dynamic studies and computed tomography (CT) scans are discussed.

Sexual ictal manifestations predominate in women with temporal lobe epilepsy A finding suggesting sexual dimorphism in the human brain

Twelve women patients with temporal lobe epilepsy reported sexual arousal or orgasm as part of epileptic seizures, usually the aura. In two patients, the sexual feelings were reproduced by stimulation of deep temporal structures. Eleven similar women have been described by other authors, and only three men. These findings suggest a different neural organization of male and female sexual function in the human brain. The sexually dimorphic structures are probably located in the limbic portion of the temporal lobe.

Serotonin synthesis rate measured in living dog brain by positron emission tomography

Abstract: In vivo measurements by positron emission tomography of the brain serotonin synthesis rates in the normal dog, in the dog with increased plasma tryptophan concentration, and in the dog under different arterial oxygen tensions are described. The method described here permits repeated measurements in the same brain for the first time. An increase in the plasma tryptophan concentration from 16.6 to 191.5 and then to 381 μM resulted in close to a linear increase in the brain serotonin synthesis rate. When PaO2 was raised from 76 ± 2 to 106 ± 1 mm Hg, the rate of serotonin synthesis in the dog brain increased from 39 ± 8 to 54 ± 10 pmol g−1 min−1. The estimates of the Michaelis‐Menten constants, Kappm and Vmax for the transport of tryptophan through the blood‐brain barrier are 303 ± 54 μM and 63 ± 10 nmol g−1, min−1, respectively.

Comparison of electrographic effects of stimulation of the amygdala and brain stem reticular formation in cats.

Abstract 1. 1. A comparison of the electrographic effects of stimulation of the amygdaloid nucleus and the brain stem reticular formation was made in 15 cats under Nembutal anaesthesia. 2. 2. Stimulation of the amygdala can produce a diffuse electrographic effect consisting of a low voltage, fast, asynchronous activity, having all the characteristics of the “arousal” pattern as produced by stimulation of the brain stem reticular formation. During such a response the barbiturate spindles are blocked and abnormal activities such as delta waves and strychnine spikes may be eliminated. A more restricted activation confined to certain cortical areas, particularly the temporal and sensori-motor cortex, is sometimes produced and more often from the amygdala than from the brain stem reticular formation. 3. 3. The electrical activity of the amygdala itself is activated in an identical way by stimulation of the reticular formation or of the opposite amygdala. This effect consists mainly in the production of a fast rhythmical type of activity, occurring often in spindles, which may represent the arousal pattern of the amygdala. This effect may occur with or without generalized cortical activation. 4. 4. Although it is as yet not possible to ascribe this activation effect to a stimulation of any particular nuclear subdivision of the amygdaloid complex, it seems clear that this effect is not obtainable from the whole amygdaloid complex, nor does it necessarily involve those nuclei receiving direct olfactory connections. 5. 5. These experimental results suggest that the amygdala, like the brain stem reticular formation and the intralaminar system of the thalamus, represents a structure capable of exerting diffuse regulatory effects on other cerebral regions. 6. 6. The role of the amygdala in epileptic automatism is discussed in the light of these findings.

Surgical treatment of intractable epilepsy associated with schizencephaly.

With the advent of magnetic resonance imaging, there has been an increased recognition of schizencephaly during life, especially in epileptic patients. We report our experience with the assessment and treatment of three patients with medically intractable seizures associated with this condition. The three men were aged 24 to 37 years. Two had delayed developmental milestones and hemiparesis or hemiplegia. One had normal development and a normal neurological examination. Seizures began between the ages of 15 and 19 years and lasted for 5 to 22 years before surgery. All had partial simple or generalized seizures with predominant electroencephalographic and electrocorticographic epileptic activity localized to temporal and frontal lobes on the side of the lesion. Neuropsychological assessment indicated widespread dysfunction maximal at the areas of predominant electroencephalographic abnormality. Magnetic resonance imaging demonstrated anterior parasagittal, parietal, and Rolandic cerebral clefts, with ventricular diverticuli, gray matter heterotopia, polymicrogyria, and a true agenesis of the corpus callosum in individual patients. The patients underwent temporal (one patient) and frontotemporal (two patients) lobectomies without additional neurological deficits or neuropsychological deterioration. Postoperative follow-up showed reduction in seizure frequency. We conclude that the surgical treatment of epilepsy is well tolerated in such patients, and their seizures can be alleviated by resection of epileptogenic areas.

Epilepsy from Cerebral Arteriovenous Malformations

Twenty-seven patients with epilepsy as the only manifestation of a cerebral AVM were seen at the MNI/MNH from 1973 to 1981. The nine females and eighteen males between the ages of fourteen and fifty-four years (mean 25.2 years) had epilepsy for an average of 3.5 years prior to the diagnosis of AVM. Seven patients had primarily generalized seizures, ten patients had partial seizures with complex symptoms, fourteen patients had partial seizures with elementary symptoms, and thirteen patients had secondarily generalized seizures. Although there was no history of intracranial hemorrhage, seven patients had negative hemispheric signs (hemiatrophy, hemianopia, dysphasia, hemiparesis), two had impaired mentation, and two were ataxic. The EEG, normal in ten cases,showed non-epileptiform activity in six cases, and focal epileptiform activity in eleven cases. Angiographic and/or histological examination revealed eight small (less than 2 cm in diameter) and nineteen large lesions. Fifteen AVMs involved the frontal lobe, ten the temporal lobe five the parietal lobe, and one the occipital lobe. Angiography failed to demonstrate three frontal and three temporal AVMs. Plain CT scanning demonstrated a high or low density lesion without a mass effect in sixteen cases, enlargement of the ipsilateral ventricle or Sylvian fissure in seven cases, and diffuse ventricular enlargement in three cases. CT scanning was performed after the intravenous injection of contrast material in nineteen cases and demonstrated vascular enhancement in fifteen cases and an abnormal blood vessel in six cases. Two angiographically occult AVMs demonstrated vascular enhancement with infusion CT scanning, thereby demonstrating the vascular nature of the lesion where angiography had failed to do so.

Clinical Patterns of Patients with Temporal Lobe Epilepsy and Pure Amygdalar Atrophy

Summary: Purpose: MRI volumetric measurements (MRIvol) have been proven reliable in determining mesial temporal atrophy in patients with TLE. We attempted to correlate the clinical features with different patterns of hippocampal formation (HF) and amygdala (AM) atrophy in patients with TLE without foreign tissue lesion.

Psychosocial Consequences of Postoperative Seizure Relief

Summary: To address the question of whether complete seizure relief has a positive effect on psychosocial functioning in patients with temporal lobe epilepsy, a follow‐up study was conducted at the Montreal Neurological Institute. The approach was one of “before‐after” study, with focus on the successfully operated patients, those in whom complete seizure relief was obtained. The Washington Psychosocial Seizure Inventory, specifically developed and validated for use with epilepsy patients, was used for psychosocial assessments. Of 30 surgically treated patients screened for the study, 15 gained complete relief from seizures. At 1‐year postoperative followup, they showed reductions in their problem scores on all but one of eight psychosocial scales; the average reduction ranged from 24% in Vocational Adjustment to 60% in Adjustment to Seizures. In the areas of Emotional Adjustment and Interpersonal Adjustment reductions were 37 and 48%, respectively. Among the component items, improvement was greatest in ability to concentrate and make decisions, confidence in interpersonal skills, ability to express personal opinions, and perception by others. No appreciable changes occurred in the 15 patients who did not gain complete relief of seizures; indeed, on six of the eight scales they showed a modest increase in their problem scores. This study provides evidence that complete relief from seizures leads to appreciable improvements in psychosocial well‐being, manifest as early as 1‐year postoperatively, in young adult patients.

Josef Klingler's models of white matter tracts: influences on neuroanatomy, neurosurgery, and neuroimaging.

During the 1930s, white matter tracts began to assume relevance for neurosurgery, especially after Cajals work. In many reviews of white matter neurobiology, the seminal contributions of Josef Klingler (1888-1963) and their neurological applications have been overlooked. In 1934 at the University of Basel under Eugen Ludwig, Klingler developed a new method of dissection based on a freezing technique for brain tissue that eloquently revealed the white matter tracts. Klingler worked with anatomists, surgeons, and other scientists, and his models and dissections of white matter tracts remain arguably the most elegant ever created. He stressed 3-dimensional anatomic relationships and laid the foundation for defining mesial temporal, limbic, insular, and thalamic fiber and functional relationships and contributed to the potential of stereotactic neurosurgery. Around 1947, Klingler was part of a Swiss-German group that independently performed the first stereotactic thalamotomies, basing their targeting and logic on Klinglers white matter studies, describing various applications of stereotaxy and showing Klinglers work integrated into a craniocerebral topographic system for targeting with external localization of eloquent brain structures and stimulation of deep thalamic nuclei. Klinglers work has received renewed interest because it is applicable for correlating the results of the fiber-mapping paradigms from diffusion tensor imaging to actual anatomic evidence. Although others have described white matter tracts, none have had as much practical impact on neuroscience as Klingers work. More importantly, Josef Klingler was an encouraging mentor, influencing neurosurgeons, neuroscientists, and brain imaging for more than three quarters of a century.