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Histological studies in botulism are primarily researched based and are not a routinely used clinical tool Structural changes produced by BTX are similar to those that result from nerve sectioning and denervation These include bouton loss, a decreased number of retracted dendritic pro les, astrocytic proliferation, and sprouting of motor nerve endings from the original terminal arborizations433,434 Motor nerve growth-simulating factor(s) released by denervated muscle may promote this sprouting435,436 The new NMJs that are formed may be near or at some distance from the original NMJ New NMJ formation enlarges the end-plate region and may result in multiple end plates on individual muscle bers from the same or different motor units The ultrastructural changes of nerve terminals are limited to the distribution of vesicles that have a log-jam appearance, suggesting impaired vesicle fusion with the presynaptic membrane437 Neurogenic muscle atrophy has also been noted in humans with inadvertent 438 and wound botulism234

Suspecting, diagnosing, and managing patients with DNMT are greatly enhanced by knowledge of both the anatomy and the physiology of normal and abnormal NMJs This unique component of the neuromuscular system represents the interface between the terminal twigs of motor nerves and the muscle bers that they innervate in mammalian skeletal muscle The NMJ serves to transduce and amplify the peripheral nerve s relatively small electrical current into a chemical signal This chemical or neurotransmitter, in turn, creates a current of suf cient intensity and proper location such that it initiates a propagating action potential in the substantially larger muscle ber Alterations in the structure and consequently the function of the various subcomponents of the NMJs are the basis of the disorders described in this chapter Regardless of the species or muscle chosen, NMJs can be subdivided into three major components: (1) the presynaptic region (2) the synaptic space or cleft, and (3) the postsynaptic region (Fig 23 6)439 DNMT arise from abnormalities in each of these locations Presynaptic DNMT may result from the reduced release of normal quanta due to impaired calcium entry into the presynaptic nerve terminal, defective synthesis or packaging of ACh into synaptic vesicles, or the diminished probability of ACh release Synaptic DNMT relate primarily to reduced or dysfunctional AChE This may occur pharmacologically or due to a genetic alteration in AChE in at least one form of congenital myasthenia Weakness in these disorders may be promoted by either continuous

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Throughout the rest of this manual, when a lab involves changing settings located in the Control Panel or the Device Manager, the directions will assume you know how to get that far, and the steps will begin with the Control Panel or Device Manager already open Refer back to this exercise if you need a refresher on opening the Control Panel

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In familial limb-girdle myasthenia, muscle biopsies may reveal tubular aggregates along with nonspeci c myopathic changes126

Muscle biopsies are not routinely performed on patients with suspected LEMS When performed, nonspeci c type II ber atrophy is an uncommon and isolated light microscopic nding196 On quantitative electron microscopic analysis, nerve terminals appear normal in both their size and the number of synaptic vesicles they contain419,428 Similarly, the postsynaptic membrane is intact but with an increase in the postsynaptic fold area and number of secondary synaptic clefts, presumably as a compensatory mechanism in response to reduced quantal release The total number and activation properties of the AChRs appear normal Freeze-fracture analysis of the presynaptic membrane demonstrates a marked decrease in the number of intramembranous proteinaceous particles, which are assumed to be P/Q voltage-gated calcium channels These presumptive channels are disorganized and aggregated in clumps165 167,429,430 432

a) To open the Control Panel, select Start | Settings | Control Panel This path applies to all versions of Windows, including Windows XP in the Classic Start menu mode The Control Panel dialog box opens, as shown in Figure 13-15 b) Start with the System applet The System applet is the gateway to many important tools and utilities you will use as a PC technician You ll explore some of these utilities in other labs throughout the manual; for now, just take a high-level view of the following:

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