Neuromuscular Disease Flashcards Preview

Neuropathology > Neuromuscular Disease > Flashcards

Flashcards in Neuromuscular Disease Deck (46):
1

PNS

Somatic components

Aff/eff limbs

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

2

PNS

Visceral components

Autonomic:

SS ganglia and nerves
PS ganglia and nerves
Eneteric plexus

3

Muscle groups

Units defined by CT

list

Epimysium = muscle

Perimysium = fascicle

Endomysium = myocytes

4

Skeletal muscle

Important cytoplasmic structures

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

5

NMJ

def

innervation point of muscle cell

6

Comparison of muscle fiber types in normal muscle

Type 1 vs type 2

Chicken meat/function


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

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

7

Comparison of muscle fiber types in normal muscle

Type 1 vs type 2

Physiologic response/size/metabolism


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

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

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)


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

9

Muscle

Dependence on innervation

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

10

Motor unit

Consists of…

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

11

Muscle

Fiber type/metabolism det’d by…

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

12

Muscle spindle

Def/fun

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

13

Muscle

Adaptation of muscle to training/work

strength training: fiber hypertrophy, primarily type 2

aerobic training: increased oxidative capacity of muscle

disuse leads to relative atrophy of type 2 fibers

14

LMN vs UMN

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.

15

Peripheral nerve

Consists of…

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.

16

Peripheral nerve

Grouped by CT

Epineurium = whole nerve

Perineurium = nerve fascicle

Endoneurium = nerve fibers

17

Peripheral nerve

Important structural features

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

18

Nerve fiber

Classification by axon size

Class/size/conduction velocity/function

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

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

19

Neurogenic atrophy

def

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

20

Neurogenic atrophy

Clinical manifestations/pathology

clinical manifestations: weakness, paralysis, atrophy

pathology: denervation of myocyte leads to atroph

21

Fiber type grouping/group atrophy of muscle

def

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

22

Examples of neurogenic muscle disease
3

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

23

Myopathies

Dysimmune/infectious myopathies

Def/examples

Damage to muscle fibers assoc with inflammation:

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

24

Myopathies

Muscular dystrophies

Definitions and examples

Inherited defects in muscle membrane/ECM components

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

25

Myopathies

Ion channel/ion transport defects

Definitions and examples

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

26

Congenital myopathies

Definitions and examples

rare inherited defects in muscle now classified according to class of molecular defect:

myofibrillar proteins: e.g., nemaline myopathy others

27

Hereditary metabolic myopathies

Definitions and examples

inherited defects in energy or intermediary metabolism:

glycogen storage disease (myopathic types)
mitochondrial myopathies
fatty acid (“lipid-storage”) diseases

28

Drug/toxic myopathies

Definitions/examples

muscle fiber damage due to effects of drug, toxin, hormone, etc.

statin myopathies
steroid myopathy…

29

Clinical features associated with myopathies

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

30

Myopathies

dx

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.

31

Myofiber necrosis

Results in…

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

32

Myofiber Regeneration

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

33

Histopathologic changes char of myopathies

list
(6)

Myofiber necrosis
Myofiber regeneration
Inflammation
Fibrosis
Structural abnormalities
Physiologic abnormalities

34

Histopathologic changes char of myopathies

fibrosis

fibrosis (fibrous scarring) of endomysium

35

Histopathologic changes char of myopathies

Structural abnormalities in myofibers

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

36

Physiologic abnormalities

selective atrophy of a fiber type

abnormal proportions of fiber types

37

Polymyositis/dermatomyositis

Mechanism

Immune-mediated:

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

38

Steroid myopathy

Forms/mech

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.

39

Muscular dystrophies

def

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

40

Wallerian degeneration

chars

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

41

Regeneration of peripheral nerves

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)

42

Segmental demyelination

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")

43

Clinical manifestations of PN

How are PN classified

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.

44

Sx of peripheral neuropathies

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

45

Patterns of involvement in peripheral neuropathies

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

46

Distinction between axonal and demyelinating neuropathies

How is it made

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