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In addition, three microscopic changes give this disease its distinctive character (Fig 39-1): (1) The presence within the nerve cell cytoplasm of thick, ber-like strands of silver-staining material, often in the form of loops, coils, or tangled masses (Alzheimer neuro brillary changes or tangles ) These strands are composed of a hyperphosphorylated form of the microtubular protein tau and appear as pairs of helical laments when studied ultrastructurally (2) Spherical deposits of amorphous material scattered throughout the cerebral cortex and most easily seen with periodic acid Schiff (PAS) and silver-staining methods; the core of the aggregates is the protein amyloid, surrounded by degenerating nerve terminals (senile or neuritic plaques) Amyloid is also scattered throughout the cerebral cortex in a nascent diffuse form, without organization or core formation and appreciated mainly by immunohistochemical methods, as well as in the walls of small blood.

Imaging techniques computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound enable one to measure

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The fundamental laws of physics. mechanics,electricity, and thermodynamicsare usually' basedon empirical observationsthat explain variations in physical properties and statesof i' systems.Rather than describing the stateof physical systemsdirectly, the laws are usually_ .r" *F '* , couched in terms of spatial and temporal changes. These laws define mechallt** .oj ., momentum, differenliol change.When combined with continuity laws for enorgy,mass,or resultsin matheequations of result.Subsequent integration thesedifferential equations " in termsof energy, the matical functionsthat describe spatialand temporalstateof a syslem -, '" As mass,or velocity variations. in Fig. FT6,1, the integrationcan be implementedanalyti* l,, cally with calculus or numericalli with the computer jumper problem introThe free-fallingbungee of of ducedin Chap. I is an example the derivation a ditferential equationfrom a fundamentallaw. Recall that Newton's second law was used to develop an ODE describingthe rate of changeof velocity of a'" jumper: falling bungee du c,t t

ered to be stunned by moderate ischemia and subject to salvage if blood ow is restored in a certain period of time. As with all infarction, the duration of ischemia plays a role. Olsen and colleagues have been able to demonstrate hypoperfused penumbral zones but, interestingly, found that regions just adjacent to them are hyperperfused. Furthermore, these investigators and others have shown that elevating the systemic blood pressure or improving the rheologic ow properties of blood in small vessels by hemodilution improves ow in the penumbra; however, attempts to use these techniques in clinical work have met with mixed success. The phenomenon of cerebrovascular autoregulation is appropriately introduced here. Over a range of mean blood pressures of approximately 50 to 150 mm Hg, the small pial vessels are able to dilate and to constrict in order to maintain CBF in a relatively narrow range. This accommodation eventually fails at the extremes of blood pressure, after which CBF follows systemic pressure passively, either falling precipitously or rising to levels that damage small vessel walls. The conditions in which the limits of autoregulation are exceeded are at the extremes of hypertensive encephalopathy at one end and circulatory failure at the other, both of which are discussed in later sections of the chapter.

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