Dysinnervation abnormalities

Denervation and dysinnervation abnormalities are usually neurogenous (but, atypically, sometimes can be myogenous see Chapter 1). Conceptually, denervation is a complete loss of neural influence on the muscle fiber (which initially can be reversible by... 

These are postulated as adversely influencing mainly the type-2 fibers (or sub-preferentially the type-2B fibers). Hypothetically, "pan-denervations" are due to (a) abnormality of both type-2 and type-1 LMNs or of their intimately related, respectively type-2 and type-1 Schwann cells (which are nurturing the LMNs and being nurtured by them). This results in lack of trophic influence on "all" the muscle fibers, either (i) fully (in pan-denervations) or (ii) partially deficient - quantitatively or qualitatively - (in pan-dysinnervations), to which the type-2 muscle fibers (or sub-preferentially type-2B fibers) are more susceptible or (b) hypothetically, relatively selective abnormality at the level of the presumed type-2 LMNs, or of their closely associated Schwann cells that we designate as "type-2 (or type-2B) Schwann... 

Type-2 muscle fiber atrophy can be cansed by varions abnormalities, snch as cachexia, hypoactivity (disnse), glncocorticoid excess, hyperparathyroidism, a manifestation of recent pan-deinnervation [51, 52] or pan-dysinnervation, or npper-motor-nenron abnormality (for extensive discnssion, see Chapter 1). 

Comment A common association of type-2 fiber atrophy (discussed in Chapter 1) is an aspect of a lower-motor-neuron abnormality resulting in functional "dysinnervation," as may be part of the pathogenic mechanism in this patient. Note that routine diagnostic EMG cannot quantify the size of the type-2 muscle-fiber fast-twitch units because they are activated only by vigorous contraction, whereas slow-twitch type-1 motor-units are activated by... 

In our cultured muscle fibers of h-IBM due to a GNB mutation, the presumably genetically determined increase of A 3PP/A 3 preceded other IBM-type abnormalities [221], including (a) their inability to become properly innervated by normal fetal spinal cord neurons, and (b) having morphologically abnormal NMJs [221]. We therefore postulated that spontaneous A 3PP/A 3 overexpression in s-IBM patient muscle may be responsible for a "myogenous dysinnervation" [221] and for the observed NMJ structural abnormalities [220] (see above), and, by analogy, the same A 3PP/AP-based mechanism may be occurring in h-IBM. 

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