Sumio Uematsu

High-frequency EEG activity at the start of seizures

Frequencies above 35-40 Hz are poorly visualized on conventional EEG scalp recordings. We investigated frequency components up to 150 Hz in digitally recorded EEGs of seizures in five patients with implanted subdural grids, as part of their evaluation for epilepsy surgery. Amplifier bandpass was set from 0.1 to 300 Hz, and EEG was digitized at 2,000 samples per second. Seizures with electrodecremental patterns at the start showed a significant increase in spectral power above 35 Hz, with a twofold increase in the 40-50-Hz range, and up to a fivefold increase in the 80-120-Hz portion of the spectrum. Activity above 40 Hz could represent summed action potentials, harmonics of synaptic potentials or transient sharp components of synaptic potentials. High-frequency increases were largely localized to the region of the seizure focus. Grid sites remote from the focus did not show significant energy in the EEG band above 40 Hz at baseline, nor at time of seizure onset. Our findings suggest that high-frequency recordings may be of use in localizing seizure foci.

Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures.

Summary: Stimulation of centromedian (CM) thalamic nuclei has been proposed as a treatment for seizures. We implanted programmable subcutaneous (s.c.) stimulators into CM bilaterally in 7 patients with intractable epilepsy to test feasibility and safety. Stimulation was on or off in 3‐month blocks, with a 3‐month washout period in a double‐blind, cross‐over protocol. Stimuli were delivered as 9O‐μs pulses at 65 pulses/s, 1 min of each 5 min for 2 h/day, with voltage set to half the sensory threshold. Stimulation was safe and well‐tolerated, with a mean reduction of tonic‐clonic seizure frequency of 30% with respect to baseline when stimulator was on versus a decrease of 8% when the stimulator was off. There was no improvement in total number of generalized seizures with stimulation, and treatment differences were not statistically significant. Stimulation at low intensity did not alter the EEG acutely, but high‐intensity stimulation induced slow waves or 2–3 Hz spike‐waves with ipsilateral frontal maximum. In an open‐label follow‐up segment with stimulator trains continuing for 24 h/day, 3 of 6 patients reported at least a 50% decrease in seizure frequency. There were no side effects. This pilot project demonstrated the feasibility of controlled study of thalamic stimulation in epilepsy, but further study will be needed to demonstrate efficacy.

Parameters for direct cortical electrical stimulation in the human: histopathologic confirmation

Safe parameters for electrical cortical stimulation in humans are difficult to estimate from the animal experimental literature. We therefore examined the light microscopic histology at a total of 11 sites of direct subdural electrical stimulation, taken as part of anterior temporal lobectomies in 3 patients. Stimulations had been done through 3.175 mm diameter electrodes, with 0.3 msec square wave pulses of alternating polarity at 50 pulses/sec. In 2 patients, one site each had been used as a common reference for stimulation, receiving over 251 stimulation trials, most of 2-5 sec duration, at currents of 12.5-15.0 mA, 1 day prior to resection. The maximum charge per phase was 4.0-4.4 microC; the maximum charge density was 52-57 microC per geometric cm2 per pulse at the electrode surfaces. Comparison of hematoxylin and eosin, periodic acid-Schiff, and cresyl violet-stained material from the electrode sites with that from other regions did not show any histologic abnormalities attributable to the electrical stimulation. The relatively brief and intermittent periods utilized for human stimulation testing do not appear to cause structural damage at the light microscopic level at charge densities that exceed the threshold for damage established in animal studies with more continuous, chronic stimulation schedules.

Functional significance of the mu rhythm of human cortex: an electrophysiologic study with subdural electrodes ☆

The existence of the mu rhythm and its general anatomical and physiological relationships are well known. There are few data, however, regarding the details of its anatomical and physiological specificity. We implanted fronto-temporal subdural electrode grids in 9 patients with intractable epilepsy to facilitate their surgical management. A 7-11 Hz cortical mu rhythm was observed in 5-16 electrodes located over the sensorimotor cortex as mapped by electrical stimulation. The mu rhythm was blocked by contralateral face and arm movements, passive movements of contralateral arm, and by ipsilateral arm movements. There was correspondence between the body area movement of which blocked the mu at a given site and the body region that was affected by stimulation at the same site. Power spectral analysis showed an overall decrease in power in all frequency bands. This was less prominent in the 14-100 Hz band resulting in a relative increase in high frequency power in association with movement. We conclude that both the presence and blocking of mu rhythm are specific to the somatic representation of the cortex from which it is recorded. Its functional significance may be similar to other sensory rhythms like the occipital alpha rhythm.

Motor and sensory cortex in humans: Topography studied with chronic subdural stimulation

Classic neurosurgical teaching holds that once the Rolandic fissure (Rf) has been located, there are distinct differentiated primary motor and sensory functional units confined within a narrow cortical strip: Brodmanns Areas 4 and 6 for primary motor units in front of the Rf and 3, 1, and 2 for sensory units behind the Rf. To test this assumption, we examined in detail the records of cortical mapping done by electrical stimulation of the cerebral cortex via implanted subdural electrode grids in 35 patients with seizure disorders. Of 1381 stimulations of the electrode sites, 346 (25.1%) produced primary motor or motor-arrest and sensory responses in contralateral body parts: 56.8% were primary motor responses; 16.2% were motor-arrest; 22.5% were sensory; and the remaining 4.5% were mixed motor and sensory responses. Two-thirds (65.9%) of the primary motor responses were located within 10 mm of the Rf, and the remaining one-third (34.1%) were more than 10 mm anterior to the Rf or were posterior to the Rf. Furthermore, in the patient group with brain lesions, fewer than one-third (28.1%) of the responses were within the 10-mm narrow anterior strip. Our study reconfirmed that a significant number--at least one-third--of motor responses are distributed outside the classic narrow cortical strip. In patients with brain lesions, the motor representation is further displaced outside the narrow strip. This finding indicates that primary motor cortex may extend beyond the gyrus immediately anterior to the Rf.

Does the central sulcus divide motor and sensory functions ? Cortical mapping of human hand areas as revealed by electrical stimulation through subdural grid electrodes

To clarify the exact anatomic relationship of electrically identified hand areas to the central sulcus, we constructed cortical surface renderings of magnetic resonance images (MRI) to locate the central sulcus accurately and measured the distances of stimulated points from, the central sulcus and the Sylvian fissure.We obtained hand responses in 33 patients who underwent implantation of subdural grid electrodes for evaluation and surgical treatment of intractable epilepsy and analyzed these responses according to the presence of motor, sensory, mixed motor and sensory, and arrest responses. Hand motor responses occurred not only in the precentral gyrus but also in the postcentral gyrus, with great variability in superior-to-inferior distribution. Sensory responses also occurred in both the precentral and postcentral gyri with a distribution more ventral than that of motor responses. Mixed motor and sensory responses tended to be limited to the middle part of the central sulcus. Sites where electrical stimulation arrested simple hand repetitive voluntary movements occurred widely throughout the premotor and primary sensorimotor cortices. These data indicate a marked variability in the location of the human cortical hand area, and suggest that motor and sensory hand cortices overlap and are not divided in a simple manner by the central sulcus. NEUROLOGY 1996,46 360-367

Characterization of the basal temporal language area in patients with left temporal lobe epilepsy

We evaluated 5 consecutive patients with subdural grid electrodes (including placement over the left basal temporal region) for focal resections for control of intractable epilepsy. All 5 had language dysfunction when we performed cortical stimulation over the basal temporal region (the inferior temporal gyrus, the fusiform gyrus, or the parahippocampal gyrus) using a systematic battery of language tests. The area in which language interference could be produced began from at least 11 to 35 mm posterior to the temporal tip and ended at least 39 to 74 mm posterior to the temporal tip. The most consistently impaired language tasks were spontaneous speech and passage reading, but there was impairment of all language functions tested in some patients. Language deficits after dominant temporal lobectomy may result from resection of this area.

Cognitive Effects of Resecting Basal Temporal Language Areas

Summary: Electrical stimulation of the basal temporal region of the dominant hemisphere before partial temporal lobectomy for epilepsy sometimes produces temporary interruption of language function, but the significance of removal of this area is unknown. We evaluated the correlation between resection of the basal temporal language areas (BTLA) and certain types of postoperative language deficits. In a population of 25 patients, we mapped the inferolateral temporal lobe with cortical electrical stimulation, verifying the positions of the stimulating electrodes with three‐dimensional computed tomography (CT). Eighty percent of the patients developed transient language deficits with stimulation, particularly with tests of confrontation naming and comprehension. BTLA was primarily located in the fusiform gyrus, from 1 to 9 cm from the temporal tip. At testing 6–12 months after operation, patients with BTLA resection performed worse (mean 9% decrease) than those with no BTLA resection (mean 4% improvement) on tests of confrontation naming (p = 0.03). Resection size accounted for less of the variance in decrease in confrontation naming than did resection of the BTLA. Tests of performance I.Q. (PIQ), verbal I.Q. (VIQ), or recognition memory for word and verbal learning showed no significant difference between these groups. Most patients do not have language decrease with removal of basal temporal lobe 5–6 cm from the tip, even with removal of BTLA. Some patients, however, have persistent decrease in naming.

Endothelin-1 receptor binding and cellular signal transduction in cultured human brain endothelial cells.

Abstract: The kinetic properties of endothelin‐1 (ET‐1) binding sites and the production of inositol phosphates (IPs; IP1, IP2, IP3), cyclic AMP, thromboxane B2, and prostaglandin F2α induced by various endothelins (ET‐1, ET‐2, ET‐3, and sarafotoxin S6b) were examined in endothelial cells derived from human brain microvessels (HBECs). The presence of both high‐ and low‐affinity binding sites for ET‐1 with KD1 = 122 pM and KD2 = 31 nM, and Bmax1 = 124 fmol/mg of protein and Bmax2 = 909 fmol/mg of protein, respectively, was demonstrated on intact HBECs. ET‐1 dose‐dependently stimulated IP accumulation with EC50 (IP3) = 0.79 nM, whereas ET‐3 was ineffective. The order of potency for displacing ET‐1 from high‐affinity binding sites (ET‐1 > ET‐2 > sarafotoxin S6b > ET‐3) correlated exponentially with the ability of respective ligands to induce IP3 formation. ET‐1‐induced IP3 formation by HBEC was inhibited by the ETA receptor antagonist, BQ123. The protein kinase C activator phorbol myristate ester dose‐dependently inhibited the ET‐1‐stimulated production of IPs, whereas pertussis toxin was ineffective. Cyclic AMP production by HBECs was enhanced by both phorbol myristate ester and ET‐1, and potentiated by combined treatment with ET‐1 and phorbol myristate ester. Data indicate that protein kinase C plays a role in regulating the ET‐1‐induced activation of phospholipase C, whereas interaction of different messenger systems may regulate ET‐1‐induced accumulation of cyclic AMP. ET‐1 also stimulated endothelial prostaglandin F2α production, suggesting that activation of phospholipase A2 is most likely secondary to IP3‐mediated intracellular calcium mobilization because both ET‐1‐induced IP3 and prostaglandin F2α were inhibited by BQ123. These findings are the first demonstration of ET‐1 (ETA‐type) receptors linked to phospholipase C and phospholipase A2 activation in HBECs.

Progressive Unilateral Encephalopathy of Childhood (Rasmussen's Syndrome): A Reappraisal

Summary: Twelve children with Rasmussens encephalitis underwent hemispherectomy and have been followed for an average of 9.15 years. Our decision‐making process leads to early, rather than late operation. Because hemiplegia is inevitable with or without operation, earlier operation may allow such children to resume a more normal life. We postulate that earlier operation may prevent some of the intellectual decline that accompanies the continued seizures and their treatment. In view of the variable pathologic findings and lack of evidence of a viral etiology, we suggest either use of the term “progressive unilateral encephalopathy of childhood” or “Rasmussens syndrome” in recognition of its heritage.