Neuromuscular Disease Flashcards
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
PNS
Visceral components
Autonomic:
SS ganglia and nerves
PS ganglia and nerves
Eneteric plexus
Muscle groups
Units defined by CT
list
Epimysium = muscle
Perimysium = fascicle
Endomysium = myocytes
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
NMJ
def
innervation point of muscle cell
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)
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)
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
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)
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
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
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
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
LMN vs UMN
- lower motor neuron (AHC) or its axon: damage leads to flaccid (hypotonic) muscle paralysis followed by atrophy
- 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.
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.
Peripheral nerve
Grouped by CT
Epineurium = whole nerve
Perineurium = nerve fascicle
Endoneurium = nerve fibers
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
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
Neurogenic atrophy
def
Neurogenic atrophy of skeletal muscle: skeletal muscle dysfunction due to abnormalities in its innervation
Neurogenic atrophy
Clinical manifestations/pathology
clinical manifestations: weakness, paralysis, atrophy
pathology: denervation of myocyte leads to atroph
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
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
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
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
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)
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
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
Drug/toxic myopathies
Definitions/examples
muscle fiber damage due to effects of drug, toxin, hormone, etc.
statin myopathies
steroid myopathy…
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
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.
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
Myofiber Regeneration
myofiber regeneration (“basophilic fibers”) from proliferation and differentiation of stem cells (satellite cells) in muscle, follows necrosis
Histopathologic changes char of myopathies
list
6
Myofiber necrosis Myofiber regeneration Inflammation Fibrosis Structural abnormalities Physiologic abnormalities
Histopathologic changes char of myopathies
fibrosis
fibrosis (fibrous scarring) of endomysium
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
Physiologic abnormalities
selective atrophy of a fiber type
abnormal proportions of fiber types
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
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.
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
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
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)
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”)
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.
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
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
Distinction between axonal and demyelinating neuropathies
How is it made
Distinction between axonal and demyelinating neuropathies can often be made with electrodiagnostic studies.
