Neuromuscular Disease

Question 1

PNS

Somatic components

Aff/eff limbs

Answer 1

Aff
DRG 
Peripheral sensory receptors
Peripheral nerve
Dorsal roots

Eff
Lower motor neuron
Skeletal muscle fibers:
extrafusal fibers
intrafusal fibers (muscle spindle)
Peripheral nerve
Ventral roots

Question 2

PNS

Visceral components

Answer 2

Autonomic:

SS ganglia and nerves
PS ganglia and nerves
Eneteric plexus

Question 3

Muscle groups

Units defined by CT

list

Answer 3

Epimysium = muscle

Perimysium = fascicle

Endomysium = myocytes

Question 4

Skeletal muscle

Important cytoplasmic structures

Answer 4

myofibril: chains of contractile proteins arranged in sarcomeres
sarcomere: unit of contractile protein (Z band to Z band)

T tubule: calcium channeling system

sarcolemma: external cell membrane containing specialized proteins

Question 5

NMJ

def

Answer 5

innervation point of muscle cell

Question 6

Comparison of muscle fiber types in normal muscle

Type 1 vs type 2

Chicken meat/function

Answer 6

Type 1
Chicken meat: Red (more myoglobin)
Function: Sustained work (non-fatigable)

Type 2
Chicken meat: White (more glycogen)
Function: Sporadic work (fatigable)

Question 7

Comparison of muscle fiber types in normal muscle

Type 1 vs type 2

Physiologic response/size/metabolism

Answer 7

Type 1
Physiologic response: Slow twitch
Size: Smaller
Metabolism: Oxidative

Type 2
Physiologic response: Fast twitch
Size: Larger
Metabolism: Mixed (2A), glycolytic (2B)

Question 8

Comparison of muscle fiber types in normal muscle

Type 1 vs type 2

Mitochondria/glycogen content/lipid content/capillary density/ ATPase stain (pH 9.4)

Answer 8

Type 1
Mitochondria: Many
Glycogen content: Low
Lipid content: High
Capillary density: High
ATPase stain (pH 9.4): Light

Type 2
Mitochondria: Few
Glycogen content: High
Lipid content: Low
Capillary density: Low
ATPase stain (pH 9.4): dark

Question 9

Muscle

Dependence on innervation

Answer 9

muscle is dependent on its innervation for voluntary contraction and maintenance of myocyte size, fiber type, & function (trophic effect of nerve cell)

Question 10

Motor unit

Consists of…

Answer 10

motor unit consists of the AHC and all muscle cells innervated by it: size varies based on degree of control necessary for muscle

Question 11

Muscle

Fiber type/metabolism det’d by…

Answer 11

fiber type/metabolism is determined by the AHC: all muscle cells innervated by the same AHC have the same fiber type

Question 12

Muscle spindle

Def/fun

Answer 12

muscle spindle: an encapsulated group of specialized muscle fibers (intrafusal fibers) with sensory and motor innervation: involved in primary myotatic reflex arc(“stretch reflex”) and maintenance of muscle tone

Question 13

Muscle

Adaptation of muscle to training/work

Answer 13

strength training: fiber hypertrophy, primarily type 2

aerobic training: increased oxidative capacity of muscle

disuse leads to relative atrophy of type 2 fibers

Question 14

LMN vs UMN

Answer 14

1. lower motor neuron (AHC) or its axon: damage leads to flaccid (hypotonic) muscle paralysis followed by atrophy
2. upper motor neuron (Betz cells in primary motor cortex and axons in corticospinal tract): damage leads to paralysis of voluntary movement; muscle is initially flaccid, then becomes spastic (hypertonic) due to imbalance of central reflexes; eventual muscle atrophy is due to disuse.

Question 15

Peripheral nerve

Consists of…

Answer 15

peripheral nerve consists of bundles of myelinated and unmyelinated axons, collections of ganglion cells, and axon terminals and receptors, with their associated cells and connective tissues.

Question 16

Peripheral nerve

Grouped by CT

Answer 16

Epineurium = whole nerve

Perineurium = nerve fascicle

Endoneurium = nerve fibers

Question 17

Peripheral nerve

Important structural features

Answer 17

axon (axoplasm)

Schwann cell

myelin sheath: internode: myelin unit defined between two nodes of Ranvier node of Ranvier: axon segment between adjacent myelin sheaths

terminal/receptor: neuromuscular junction, sensory receptor

Question 18

Nerve fiber

Classification by axon size

Class/size/conduction velocity/function

α-fibers
Aα fibers
γ-fibers
Aβ, Aδ
C fibers

Answer 18

Class
Size
Conduction velocity
Function

α-fibers
Myelinated larger (13-20u)
70-120 m/s
Extrafusal muscle fibers

Aα fibers
Myelinated larger (13-20u)
70-120 m/s
Vibration, position, light touch

γ-fibers
Smaller (2-8u)
5-30 m/s
Intrafusal muscle fibers

Aβ, Aδ
Smaller (2-12u)
5-70 m/s
Sharp pain, temperature, pressure

C fibers
Unmyelinated small (0.2-1.5u)
0.5-2 m/s
Pain, automatic

Question 19

Neurogenic atrophy

def

Answer 19

Neurogenic atrophy of skeletal muscle: skeletal muscle dysfunction due to abnormalities in its innervation

Question 20

Neurogenic atrophy

Clinical manifestations/pathology

Answer 20

clinical manifestations: weakness, paralysis, atrophy

pathology: denervation of myocyte leads to atroph

Question 21

Fiber type grouping/group atrophy of muscle

def

Answer 21

ability of adjacent nerve terminals to sprout and renervate denervated myocytes leads to alteration in normal pattern of fiber typing: fiber type grouping

progression of denervating process leads to group atrophy or atrophy of whole fascicle or muscle

Question 22

Examples of neurogenic muscle disease

3

Answer 22

trauma to peripheral nerves or roots containing motor fibers

anterior horn cell (AHC) diseases
poliomyelitis (viral infection destroying AHC) amyotrophic lateral sclerosis (neurodegenerative disease)
hereditary spinal muscular atrophies (SMA)

peripheral neuropathies affecting motor nerves

Question 23

Myopathies

Dysimmune/infectious myopathies

Def/examples

Answer 23

Damage to muscle fibers assoc with inflammation:

Immune mediated diseases: polymyositis, dermatomyositis
Inclusion body myositis
Specific infections (trichinosis, viruses, bacteria)
Vasculitides

Question 24

Myopathies

Muscular dystrophies

Definitions and examples

Answer 24

Inherited defects in muscle membrane/ECM components

resulting in progressive muscle fiber damage:
dystrophinopathies (Duchenne/Becker muscular dystrophy) many others

Question 25

Myopathies Ion channel/ion transport defects Definitions and examples

Answer 25

malfunction of excitation/contraction coupling, usually due to rare genetic molecular defects, often produce myotonia (failure of relaxation of muscle following voluntary contraction)

Question 26

Congenital myopathies Definitions and examples

Answer 26

rare inherited defects in muscle now classified according to class of molecular defect: myofibrillar proteins: e.g., nemaline myopathy others

Question 27

Hereditary metabolic myopathies Definitions and examples

Answer 27

inherited defects in energy or intermediary metabolism: ``` glycogen storage disease (myopathic types) mitochondrial myopathies fatty acid (“lipid-storage”) diseases ```

Question 28

Drug/toxic myopathies Definitions/examples

Answer 28

muscle fiber damage due to effects of drug, toxin, hormone, etc. statin myopathies steroid myopathy…

Question 29

Clinical features associated with myopathies

Answer 29

``` Reflect muscle damage and dysfunction: symmetrical weakness, often proximal > distal muscles fatigability exercise intolerance muscle pain abnormal muscle tone cramps myoglobinuria elevated CK hyperkalemia ```

Question 30

Myopathies dx

Answer 30

Myopathies are usually characterized by structural abnormalities in muscle fibers that can be seen under the microscope. Many are now also diagnosed by genetic or molecular testing.

Question 31

Myofiber necrosis Results in…

Answer 31

results in release of creatine phosphokinase (CK), myoglobin, potassium. rhabdomyolysis: syndrome of acute massive muscle fiber necrosis, often characterized by prominent myoglobinuria, can lead to renal failure

Question 32

Myofiber Regeneration

Answer 32

myofiber regeneration (“basophilic fibers”) from proliferation and differentiation of stem cells (satellite cells) in muscle, follows necrosis

Question 33

Histopathologic changes char of myopathies | list 6

Answer 33

``` Myofiber necrosis Myofiber regeneration Inflammation Fibrosis Structural abnormalities Physiologic abnormalities ```

Question 34

Histopathologic changes char of myopathies fibrosis

Answer 34

fibrosis (fibrous scarring) of endomysium

Question 35

Histopathologic changes char of myopathies Structural abnormalities in myofibers

Answer 35

storage material (e.g., glycogen, lipid). increased mitochondria: "ragged red fibers" abnormalities in structure of sarcomeres, abnormal cytoplasmic inclusions, etc., (often characteristic for particular congenital, toxic, or drug-induced myopathies) Histopathologic changes char of myopathies

Question 36

Physiologic abnormalities

Answer 36

selective atrophy of a fiber type abnormal proportions of fiber types

Question 37

Polymyositis/dermatomyositis Mechanism

Answer 37

Immune-mediated: PM: autoinvasive CD8+ T cells attack muscle cells directly DM: antibody- or immune complex-mediated microangiopathy with secondary muscle damage

Question 38

Steroid myopathy Forms/mech

Answer 38

forms: iatrogenic; endocrinopathy (Cushing’s disease) mechanism: steroids probably impair of muscle protein/ carbohydrate metabolism due to insulin resistance and protein catabolism and cause selective atrophy of type 2 fibers.

Question 39

Muscular dystrophies def

Answer 39

Definition: heterogeneous group of inherited progressive degenerative myopathies associated with muscle fiber loss and replacement by connective tissue (endomysial fibrosis) * dystrophinopathies (Duchenne-Becker): are the most common

Question 40

Wallerian degeneration chars

Answer 40

Degeneration of axon distal to site of damage/transection * Myelin sheath disintegrates secondarily to axon loss * NOTE: transection of axon proximally may lead to death of nerve cell * Cord of residual Schwann cells (band of Bungner) persists at site of lost axon for a time after degeneration of the axon and can facilitate regrowth of axon

Question 41

Regeneration of peripheral nerves

Answer 41

Regrowth of axons along cords of residual Schwann cells: growth rate <2mm/day. * May be effective in restoring much of nerve function if connections are re-established * Aberrant regeneration may form a disorganized tumor-like mass of nerve fibers, Schwann cells and scar tissue (traumatic neuroma) Distal axonal degeneration (“dying back neuropathy”) Slow loss of axons over time, usually involving longest axons and beginning distally * Distal end of axon may appear swollen (a form of neuroaxonal dystrophy)

Question 42

Segmental demyelination

Answer 42

Damage or loss of myelin internodes along length of axon/nerve * Schwann cells may remyelinate the axon, but remyelinated segments may not conduct as efficiently as normal segments * Progressive episodes of demyelination and remyelination produce onion bulb formations (concentric proliferation of Schwann cells and collagen around nerve fiber) leading to enlargement of nerve fascicle ("hypertrophic neuropathy")

Question 43

Clinical manifestations of PN How are PN classified

Answer 43

Neuropathies are classified by the type of nerve involved (motor, sensory, autonomic), the anatomic pattern of involvement, the clinical time course (acute, subacute, chronic), and whether the pathologic process appears to involve primarily the axon or the myelin sheath.

Question 44

Sx of peripheral neuropathies

Answer 44

a. loss of function: weakness, sensory loss, hyporeflexia/areflexia, impaired autonomic function, etc. b. exaggerated/distorted function: pain, dysesthesias (abnormal sensations) c. musculoskeletal deformities (kyphoscoliosis, pes cavus, etc.), especially when the PN is present during development

Question 45

Patterns of involvement in peripheral neuropathies

Answer 45

a. mononeuropathy: involvement of one nerve b. mononeuropathy multiplex: involvement of several separate nerves, usually asymmetric and involving different areas of body c. polyneuropathy: symmetric involvement of multiple nerves usually in particular regions: e.g., “stocking-glove pattern” in distal neuropathy

Question 46

Distinction between axonal and demyelinating neuropathies How is it made

Answer 46

Distinction between axonal and demyelinating neuropathies can often be made with electrodiagnostic studies.