L12 Neuromuscular Disorders

Question 1

What is a motor unit?

Answer 1

a single alpha motoneuron and all the muscle fibers innervated by that alpha motoneuron

Question 2

What are four important things to know about motor unit recruitment?

Answer 2

Muscles used for more precise motor movements, in general, have larger numbers of smaller motor units that muscles used for larger motor movements

Within any given muscle, there is a range of motor unit sizes

The smaller motor units innervating a particular muscle are preferentially activated for small motor movements

For larger motor movements, both small and larger motor units are activated

Question 3

What are the three types of skeletal muscle?

How are they differentiated?

Answer 3

Composed of fibers that differ in function and enzymatic composition:

Type 1: slow twitch, oxidative

Type 2A: fast twitch, oxidative/glycolytic

Type 2B: fast twitch, glycolytic

Histochemical techniques are used to differentiate the 3 types

Differentiation into one of 3 types depends in part on history of activation, small motor units that are more persistently activated fibers tend to be Type 1. Larger motor units tend to be Type 2A or B

All fibers belonging to a given motor unit have the same history of activation, all fibers belonging to a given motor unit are of the same fiber type

Question 4

How does the size of alpha motorneurons affect the mechanism of motor unit recruitment?

Answer 4

alpha motor neurons that have serveral branches to innervate several muscle fibers (larger motor units) also have larger cell bodies than smaller alpha motorneurons that have fewer branches and innervate fewer muscle fibers (small motor units)

Question 5

What happens when we decide to perform a voluntary movement?

Answer 5

Motor control centers in the brain send down impulses that lead to the release of an excitatory neurotrasmitter (producing a depolarization) onto each of the alpha motorneurons innervating a given skeletal muscle

The amount of neurotransmitter released is directly related to the magnitude of force we wish to generate during hte motor movement

Question 6

What determines whether the alpha motor neuron will fire an action potential?

Answer 6

The transmitter is released onto the dendrites of the alpha motorneuron, and the action potential is initiated only at teh axon hillock of the alpha motorneuron, the degree of depolarization produced by a neurotransmitter and the extent to which that depolarization is conducted to the axon hillock determines whether or not the alpha motorneuron will fire an action potential

Question 7

How does the size of alpha motoneuron cell bodies affect the action potential?

Answer 7

Large cell bodies provide a large area of membrane that must be charged before the depolarizing synaptic current at the dendrites can reach the axon hillock

As a result, a rather large proportion of the depolarizing capacitative current generated by depolarization at the dendrites is used up in charging the cell body and is not available for depolarizing the axon hillock

The axon hillock of smaller cell bodies will always receive a larger proportion of the current that is produced by dendrtitic depolarization and are more likley to fire an action potential when small amounts of neurotransmitter are released at the dendrites (smaller motor movements)

Question 8

What is the primary classification step in differentiating disorders of peripheral nerve and muscle?

Answer 8

Neurogenic: originate as a fundamental disorder of the nerve

Myogenic: originate as fundamental disorder of the muscle

Question 9

What are the two subclassificatoins of neurogenic disorders?

Answer 9

Motor neuron diseases and Peripheral neuropathies

Question 10

What are motor neuron diseases?

Answer 10

Subclassification of neurogenic disorders which originate from a fundamental dysfunction of the entire cell body of a neuron and which may result in cell death

These are further subclassified into:

upper motoneuron diseases associated with the dysfunction or degeneration of those motor neurons in the brain responsible for activating alpha motoneurons

lower motoneuron diseases which are characterized by the dysfunction and/or degeneration of alpha motoneurons

Question 11

What motor neuron disease is classified as both an upper and lower motor neuron disease?

Answer 11

Amyotrophic lateral sclerosis or Lou Gehrig’s disease

Question 12

What is a peripheral neuropathy?

Answer 12

A subclassification of neurogenic disorders that originate from a fundamental dysfunction of the axon and can be further distinguished into:

axonal neuropathies: produced by difficulties in sustaining the metabolic activities of the axon and which may result in axonal degeneration or death by a dying back phenomenon

demyelinating neuropathies: characterized by the loss or improper growth or maintainence of the myelin sheath and which result in conduction abnormalities

Question 13

How does muscle weakness help differentiate between myopathies and neuropathies?

Answer 13

Distal limb weakness: neuropathy

Proximal limb weakness: myopathy

Question 14

What are muscle fasciculations?

Answer 14

Twitches produced by spontaneous activation of individual motor units

Mechanism involves the spontaneous appearance of an action potential at a super excitable nerve terminal and the subsequent conduction of an action potential back down the axon and into the nerve termal branches of the alpha motoneuron

Result is a nearly simultaneous twitch of all the fibers in a given motor unit

Characteristic of organophosphate poisoning and lower motor unit disorders

Question 15

What are muscle fibrillations?

Answer 15

Twitches produced by activation of individual muscle fibers

Mechanism invovles appearance of an action potential at a muscle fiber that is produced by some superexcitability of the muscle fiber membrane

This may occur when a single impulse arriving at the nerve terminal produces a single EPP that because of muscle fiber hyperexcitability produces multiple aciton potentials and consequent multiple twitches or a partially fused tetanic contraction

Question 16

What is a disease characterized by muscle fiber hyperexcitability?

Answer 16

Myotonia

The hyperexcitability may be produced either by a decrease in the conductance to Cl- and/or a deficit in Na+ channel inactivation

Question 17

What are spinal reflexes?

What is the stretch reflex?

Answer 17

Spinal reflexes involve feedback pathways between sensory elements that monitor the length or tension of skeletal muscle and the alpha motoneurons that control the contraction of these skeletal muscles

In the stretch reflex, specialized sense organs monitor external length of the muscle and are activated when the muscle is lengthened beyond a specific value (set point)

Activation of these sense organs produces one or more action potentials which are then conducted back into the spinal cord and into nerve terminals which release an excitatory neurotransmitter onto the alpha motoneurons which in turn produce muscle contraction and external muscle shortening

Question 18

What is the knee jerk or patellar tendon reflex?

Answer 18

A physical examination which assesses the stretch reflex

normal contractile responses= normoreflexive

vigorous or sustained contractions= hyperreflextive

small or delayed contractions=hyporeflexive

Question 19

What kinds of disorders are hyperreflexia and hyporeflexia associated with?

Answer 19

Hyperreflexia: landmark indication of an upper motor neuron deficit that could be produced by an actual upper motor neuron disease or by any damage to the descending control pathways that conduct impulses to the alpha motoneurons

Hyporeflexia: characteristic of a variety of abnormalities as diverse as spinal shock (shutdown of reflexes following spinal cord injury) and myopathies (deficits in contractile response)

Question 20

What is the distinction between muscle atrophy and muscle necrosis?

Answer 20

They are both characterized by decreases in the external size of skeletal muscles and in obvious muscle weakness

However, the histological appearance of these two symptoms are different

In cross section, atrophic muscle is characterized by several abnormally small diameter muscle fibers that may or may not be surrounded by normal or extremely large fibers

Question 21

What is muscle atrophy and indicator of?

Answer 21

A disruption in the neurotropic influence of a nerve on muscle that is mediated by nerve induced changes in muscle activity and by a decrease in the release of neurotropic substances into the region surrounding individual muscle fibers (basal lamina)

Characterized by limitations in neurotropic influences due to axonal neuropathies affecting alpha motoneurons or to lower motor neuron diseases

Also results from inactivity without defects in nerve function

Question 22

How is muscle necrosis characterized?

Answer 22

By very small, non-functional, necrotic fibers, large hypercontracted fibers, macrophage infiltration, and infiltration with fat and connective tissue

Landmark indicator of myopathies such as Duchenne and related muscular dystrophies

Question 23

What is a histological indicator of neuropathies characterized by periods of denervation?

What is fiber type grouping?

Answer 23

In normally innervated muscle, the muscle fibers innervated by a given alpha motoneruron are interspersed throughout the muscle. Histochemically, this produces a patchwork pattern of different classes of muscle fiber types (I, IIA, IIB)

Degeneration of the synaptic terminals of some motor units is compensated by increased nerve terminal sprouting of relatively healthy motor units and the formation of new gap junctions between the healthier motor units and the original endplate regions vacated by the degenerating terminals

As a result, the few healthier motor units dominate the innervation of large sectors of muscle and produce large sections characterized by a single histochemical fiber type (fiber type grouping)

This is a strong indicator of a neuropathy characterized by periods of denervation

Question 24

How is the needle electromyogram (EMG) operated?

Answer 24

By placed a recording needle electrode in a skeletal muscle and either asking the patient to produce a strong or weak contraction of muscle or directly stimulating the nerve innervating that muscle at relatively high or low voltages

Question 25

What is the purpose of the electromyogram (EMG)?

Answer 25

The recording of the electrode is used to detect the activation of individual motor units during these contractions

The activation of small motor unites produces small compound action potentials that are produced by summing those action potentials induced in each of the muscle fibers innervated by that motor unit

Larger motor units produce larger action potentials because more muscle fibers are activated by the larger motor units

Question 26

How can EMG help differentiate between neuropathis and myopathies?

Answer 26

EMGs with abnormally large motor units (judged by the motor unit compound action potential) are characteristic of neuropathies with denervation

EMGs with abnormally small motor units are characteristic of myopathies with necrotic muscle fibers

Question 27

How do blood tests indicate myopathies?

Answer 27

Increased presence of skeletal muscle cytoplasmic enzymes such as skeletal muscle specific creatine kinase is evidence for a myopathy such as Duchenne an other muscular dystrophies

Question 28

What do peripheral nerve conduction velocity measurements tell us?

Answer 28

Conduction velocity is largely unaffected in axonal neuropathies and motor neuron diseases

Widespread, abnormal reductions in the conduction velocity of myelinated classes of axons that are not limited to areas of obvious physical nerve damage or compression are indicative of demyelinating neuropathies

Other aspects of peripheral nerve recordings are also highly characteristic of demyelinating diseases