A major feature of Alzheimer's disease (AD) pathology is the plaque composed of aggregated amyloid-β (Aβ) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric Aβ as the primary noxious form. Aβ oligomers can be generated both extracellularly and intracellularly. Aβ is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton. Current treatments for AD are limited and palliative. Much research and effort is being devoted to reducing Aβ production as an approach to slowing or preventing the development of AD. Aβ formation results from the amyloidogenic cleavage of human amyloid precursor protein (APP). Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloid.

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Summary: Purpose:We compared propofol with high-dose barbiturates in the treatment of refractory status epilepticus (RSE) and propose a protocol for the administration of propofol in RSE in adults, correlating propofol's effect with plasma levels.Methods: Sixteen patients with RSE were included; 8 were treated primarily with high-dose barbiturates and 8 were treated primarily with propofol.Results: Both groups of patients had multiple medical problems and a subsequent high mortality. A smaller but not statistically significant fraction of patients had their seizures controlled with propofol (63%) than with high-dose barbiturate therapy (82%). The time from initiation of high-dose barbiturate therapy to attainment of control of RSE was longer (123 min) than the time to attainment of seizure control in the group receiving propofol (2.6 min, p = 0.002). Plasma concentrations of propofol associated with control of SE were 14 pM +. 4 (2.5 p,g/ml). Recurrent seizures were common when propofol infusions were suddenly discontinued but not when the infusions were gradually tapered.Conclusions: If used appropriately, propofol infusions can effectively and quickly terminate many but not all episodes of RSE. Propofol is a promising agent for use in treating RSE, but more studies are required to determine its true value in comparison with other agents.

Functional magnetic resonance imaging (fMRI) was performed in seven patients harboring intracerebral gliomas proven by histological analysis using a noninvasive blood oxygen level-dependent technique based on the documented discrepancy between regional increases in blood flow and oxygen use in response to regional brain activation. We combined fMRI with conventional magnetic resonance imaging (MRI) during motor or language task activation experiments to investigate the potential usefulness of mapping regional brain activity as part of treatment planning in patients with intracerebral gliomas, in whom preservation of areas of functioning brain tissue is critical. Statistical fMRI maps were generated and directly mapped onto conventional MRI scans obtained at the same session. Of the five patients cooperative enough to remain motionless for the study and perform the task, the location of activation in the primary sensorimotor cortex on the side of the tumor was clearly displaced compared with that in the normal contralateral hemisphere in four patients. Four of the five tumors in these patients showed fMRI activation within the periphery of (or immediately adjacent to) areas of presumed tumor based on spin-echo MRI. In some patients with neurological deficit, the extent of activation was reduced on the side of the tumor as compared with the normal hemisphere. The supplemental motor area and the ipsilateral primary motor cortex were also reproducibly activated during motor tasks. We conclude that blood oxygen level-dependent fMRI can localize areas of cortical function in patients undergoing treatment planning for gliomas so that therapy can be directed away from regions of residual function. Our preliminary data suggest that functioning cortex within or adjacent to tumor margins can be demonstrated, which may correspond to partial preservation of clinical function. Our preliminary data also suggest that there may be a quantifiable difference on fMRI between activation in tumor-bearing cortex and activation in corresponding normal cortex in the contralateral hemisphere. We postulate that the magnitude of this difference may relate to the severity of patient deficit.

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This revision to the EEG Guidelines is an update incorporating current electroencephalography technology and practice. The role of the EEG in making the determination of brain death is discussed as are suggested technical criteria for making the diagnosis of electrocerebral inactivity.

Men and women with epilepsy frequently complain of sexual dysfunction. We studied the sexual response in men and women with partial epilepsy of temporal lobe origin (TLE) by measuring genital blood flow (GBF) during sexual arousal. Nine women and eight men with TLE and 12 women and seven men as controls completed inventories for symptoms of depression, sexual experience, and sexual attitude and underwent measurement of digital pulse and GBF during alternating segments of sexually neutral and erotic videotape. Subjective ratings of arousal to the videotape were obtained. We calculated digital pulse and GBF response as the percentage increase in pulse amplitude during the erotic compared with the preceding sexually neutral film. No subject group reported symptoms of significant depression on the inventory. However, men and women with epilepsy had fewer sexual experiences than subjects without epilepsy, and women with epilepsy imagined specific sexual activities to be more anxiety-producing and less arousing than did women without epilepsy. Men and women with TLE had a diminished GBF response. The mean increase in GBF in men with TLE was 184% versus 660% for controls (p = 0.01). Women with TLE had a mean increase of 117% versus 161% for controls (p < 0.01). Digital pulse did not vary across stimulus conditions. Subjective ratings for all groups indicated moderate sexual arousal. We conclude that there is a diminution in one aspect of physiologic sexual arousal in some men and women with TLE.

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