Bertorini - Non-Inflammatory Myopathies Flashcards
1
Q
What is a motor unit?
A
- A motor neuron
- Its axon
- Muscle fibers innervated by them
2
Q
What is Gower’s sign?
A
- Most comm symptom of NM disease is weakness
1. Myopathic disease: weakness primarily affects the proximal muscles - Pts have trouble getting up from the floor due to hip muscle weakness and/or weakness raising the arms above their head
1. Bc of hip muscle weakness, pt needs to use hands to raise from floor and then ”climb over his legs” in figures 2, 3, and 4 (Gower’s sign) to achieve the standing position
3
Q
What do you see here? What are these signs of?
A
- Patients w/myopathies have proximal muscle atrophy and weakness
1. Shoulder atrophy at arrow 1
2. “Winging” of the scapula at arrow 2 -> weak muscles cannot fix the scapula to the rib cage
4
Q
What is going on here?
A
- Distal leg wasting in peripheral neuropathy
- In polyneuropathies, there is distal muscle weakness and wasting (blue arrow)
- These patients typically also have decreased sensation and depressed reflexes
- Patients with motor neuron diseases (like ALS) do not have sensory deficits as those disorders affect only the motor axons
5
Q
What do you see here?
A
-
Peroneal neuropathy: left foot
1. Some neuropathies affect individual nerves and these are called mononeuropathies - Damage to the peroneal nerve on the left
- Patient was asked to dorsiflex toes of both feet -> note the inability to dorsiflex the toes of the left foot from weakness of the tibialis anterior muscle
6
Q
What is this?
A
- Myasthenia gravis: ptosis after sustained upward gaze
- Before (top) and after (bottom) period of sustained upward gaze
1. Pt develops roopy eyelids or ptosis (arrows) after sustained upward gaze -> characteristic of myasthenia gravis
2. MG: disease of neuromuscular transmission in which muscle fatigue is a hallmark
7
Q
What are the pattern of weakness and muscle stretch reflexes in motor neuron disease? Are there fasciculations or sensory loss?
A
- Pattern of weakness: Variable, symmetric in most; often asymmetric in ALS
- Muscle stretch reflexes: Variable, decreased in most; INC in ALS
- Fasciculations: Yes
- Sensory loss: No
8
Q
What are the pattern of weakness and muscle stretch reflexes in polyneuropathy? Are there fasciculations or sensory loss?
A
- Pattern of weakness: Distal > proximal
- Muscle stretch reflexes: Decreased or absent
- Fasciculations: Sometimes
- Sensory loss: Usually present
9
Q
What are the pattern of weakness and muscle stretch reflexes in diseases of NM junction? Are there fasciculations or sensory loss?
A
- Pattern of weakness: Proximal > distal, fluctuates; often involves extra-ocular muscles
- Muscle stretch reflexes: Normal in post-synaptic disorders (MG); decreased in Lambert-Eaton and botulism
- Fasciculations: No
- Sensory loss: No
10
Q
What are the pattern of weakness and muscle stretch reflexes in myopathy? Are there fasciculations or sensory loss?
A
- Pattern of weakness: Proximal > distal (in most)
- Muscle stretch reflexes: Normal initially, but may be decreased in later stages -> ankle reflexes often preserved until late
- Fasciculations: No
- Sensory loss: No
11
Q
What does this show?
A
- Normal muscle histology: normal, polygonal shape of muscle fibers and dark staining nuclei
12
Q
What is electromyography?
A
-
Electromyography: detects potentials close to a needle electrode inserted in muscle, and connected to oscilloscope
1. Analysis of characteristics of motor unit action potentials, their size, and #’s is a very important dx tool in NM disease
2. Right image: as pt contracts muscle, two MUAP’s recorded; w/INC effort, many motor units recorded, depending on level of effort -
Left image: two motor neurons and muscle fibers innervated by each motor neuron (either type I or II) -> these form the motor unit
1. When motor neuron depolarizes, it causes muscle fibers of motor unit to depolarize, and their action potentials summate, forming motor unit action potentials (MUAP’s)
13
Q
Describe normal muscle fiber-type distribution.
A
- As motor neurons innervate either type I or type II muscle fibers, they are intermixed w/ fibers from o/motor neurons in almost “checkerboard” pattern
- Image on the front is a normal muscle biopsy stained w/alkaline ATPase (T1: pale; T2: dark)
- In humans, the checkerboard pattern is seen in most muscles, with some having more of one fiber type depending on the muscle function
- Remember: a motor neuron and the fibers it innervates (motor unit) belong to only one type, and the physiological and histo characteristics are determined by motor neuron and its firing pattern
14
Q
What does this image show?
A
- When a muscle loses innervation via some injury, e.g., trauma to its axon, peripheral neuropathy or damage to the motor neuron, the muscle fibers become atrophic and angulated
- Atrophic fibers stain dark with most histochemical stains, particularly non-specific esterase, as in this slide
15
Q
What does this image show?
A
- 2 main axons that are damaged (arrows) -> axons sprouting from o/intact neurons take over and reinnervate previously denervated fibers, so more fibers of single neurons remain, forming groups of both fiber types seen histologically (attached image)
- This is fiber type grouping: action potentials generated by these will be larger, as more muscle fibers innervated by a single motor neuron will be detected by needle electrode in mm contractions using EMG recording; however, total # of action potentials will be DEC (fewer # of motor neurons)
- In peripheral nerve injury with denervation and reinnervation, there are fewer, but larger, motor unit action potentials on EMG
16
Q
What do you see here?
A
- Muscle biopsy stained with ATPase
- Normal “checkerboard” pattern appearance has been lost, and there is fiber-type grouping characteristic of chronic neurogenic diseases (peripheral neuropathy, motor neuron disease), from reinnervation
17
Q
What does this image illustrate?
A
- Motor neuron or axonal injury causes large and polyphasic motor action unit potentials
- Left: damage to motor neuron (1 thin arrow), or its axon (2 thin arrow), causes atrophic angular muscle fibers (those that produce fibrillations on EMG)
- With time shown by dark arrow progressing to right, axons from intact (dark) motor neuron innervate more muscle fibers (grouping); summation of individual muscle fiber potentials produces a larger MUAP on EMG upon muscle contractions
18
Q
What does this image show?
A
- Necrotic (pale-appearing) muscle fibers from an autoimmune myopathy
19
Q
What happens to MUAP’s in myopathies?
A
- Individual muscle fibers ill or non-functional, so when muscle contracts, the MUAP’s are smaller
- Could be “polyphasic” because of a asynchronous depolarization of individual fibers of the motor unit
- # motor units NOT decreased, unlike neurogenic disorders, bc # of motor neurons or axons normal -> it is the # of individual fibers of the motor unit that are nonfunctional or dead
- Even when muscle contraction is very weak, there is a normal number of motor unit action potentials (this might appear increased for a weak muscle)
20
Q
What is a common blood test abnormality seen in myopathies?
A
- Sick, necrotic mm fibers leak some sarcoplasmic components like creatine kinase enzymes (CK, CPK)
- Because enzymes elevated in serum, a common blood test abnormality seen in myopathies is an elevated serum CK
21
Q
What does this drawing show?
A
- Shows two normal motor neurons and axons , but sick muscle fibers -> only one fiber is healthy, so the motor unit action potential is small
- Also polyphasic because the damaged individual fibers fire asynchronously
22
Q
How do myopathies affect MUAP’s?
A
- During voluntary activity:
1. Motor unit potentials are small in size, and of short duration
2. To achieve the same strength of contraction during voluntary activity, more muscle fibers must contribute -> INC # MUAP’s as compared to strength of contraction
a. # of action potentials per contraction is NOT reduced
3. DEC # of muscle fibers per motor unit - Causes a different pattern of responses on EMG recordings than motor neuron or peripheral NN damage
23
Q
How do we measure the motor conduction velocity?
A
- Stimulation of ulnar N at wrist on left and elbow on right with recordings at the adductor digiti quinti m
- Compound muscle action potential (summation of all motor units generated by max NN stimulation) in middle image; can also observe the latencies and measure the amplitudes
1. Conduction velocities calculated by dividing distance b/t two stimulation electrodes by the difference of their latencies = distance/(latency 1 – latency 2) - Bottom image: very slow, prolonged latency and small compound muscle action potential in a demyelinating neuropathy
24
Q
How do we measure the conduction velocity of the peroneal nerve?
A
- Nerve stimulated at ankle while recording muscle action potential over the extensor digitorum brevis
1. Time it takes action potential to travel from stimulus to response sight is the distal latency - Then proximal latency measured by stimulating N at the knee
- CV (m/s) = distance (cm)/ latency difference (ms)
31
Q
What are congenital myopathies?
A
- Manifest at birth, and are hereditary
- Appear as floppy infants (weakness, hypotonia) at birth (see attached image)
- Examples: central core disease, myotubular myopathy, “nemaline” or “rod” myopathy, and congenital muscular dystrophy
35
Q
What do you see here? Yellow arrow?
A
- 3-y/o child w/Duchenne’s -> winging of scapulae, lordosis, and large calf muscles
- Muscle biopsy on the right (H&E stain): bluish fibers w/prominent nuclei -> they are regenerating fibers; also prominent connective tissue b/t fibers
1. Yellow arrow: necrotic fiber undergoing phagocytosis
36
Q
What is the difference b/t the left and right images?
A
- Normal muscle fibers on the left
- Atrophic muscle fibers with lack of dystrophin on the right
- Immunoperoxidase stain for dystrophin –> notice normal staining in mm membrane in a control (left), and a very abnormal muscle without dystrophin from a child with Duchenne’s dystrophy (right)
38
Q
What is exon skipping?
A
- Restores the reading frame, producing a message that although smaller, makes sense, so this could be a smaller yet functional protein
- Novel treatment of several inherited diseases like Duchenne’s dystrophy
- Attached image shows mm biopsy of animal model of Duchenne’s -> lack of staining in top mm biopsy, & restoration after injection of a morpholino, an anti-sense oligonucleotide that restores reading frame
- This therapy is now being tested in human muscle, restoring dystrophin in Duchenne’s children
39
Q
What is going on here?
A
- Pt w/Becker’s muscular dystrophy
1. Older than the children with Duchenne’s dystrophy (milder disease)
2. Note lordosis and the calf hypertrophy - Right: muscle biopsy of Becker’s patient stained for dystrophin
1. Several mm fibers still have the protein, i.e., not an absence as in Duchenne’s dystrophy
40
Q
What are myotonic dystrophies?
A
- Auto dom diseases characterized by weakness and myotonia -> can involve multiple organs
-
Anticipation w/INC repeat expansions, more severe phenotypes in younger generations
- Features: percussion and grip myotonia, facial, neck, and distal weakness, cataracts, balding, diabetes, central sleep apnea, megaesophagus and megacolon, heart conduction defects, mental retardation in newborns of myotonic mothers (congenital myotonic dystrophy) - Note elongated faces in attached image
- Genetic defect: increased CGT repeats of DNA on chromosome 19, which encodes a protein kinase - Proximal myotonic dystrophy is similar, but has proximal weakness & a different genotype (change in chromosome 3)
43
Q
What is McArdle’s disease?
A
- Muscle pains during exercise caused by muscle phosphorylase deficiency from which glycogen can not break down during exercise to produce ATP, lactate and pyruvate necessary for oxidative metabolism
- Measurement of serum lactate shows lack of normal increase, particularly during ischemic exercise when glycogenolysis is normally utilized as an energy source
44
Q
What is going on in these three images?
A
- Normal phosphorylase on left
- Phosphorylase deficiency: biopsy of pt w/McArdle’s -> blood vessels, but not muscle stain +, unlike normal muscle on the left
- Glycogen accumulation: PAS stain showing glycogen accumulation in border (subsarcolemmal area) of the fibers
47
Q
What are the events of NM transmission?
A
- a) Ach vesicles in N terminal
- b) Nerve action potential
- c) Voltage-gated Ca channels that open after the arrival of the nerve action potential
- d) Opening of Ca channel initiates complex mech of Ach release at NM junction
- e) Ach molecules attach to their receptor in the muscle area of the junction, triggering opening of its ionic channel; produces end plate potential (EPP).
- f) If EPP is of sufficient magnitude, causes opening of muscle sodium channels, which initiates a muscle action potential that propagates and then triggers the mechanism of muscle contraction
1. Spontaneous release of acetylcholine that does not trigger a muscle action potential is called a miniature end plate potential (MEPP) - Ach removed from synaptic cleft via hydrolysis by cholinesterase to choline and acetate and passive diffusion of the neurotransmitter from the area; choline is then transported actively to the nerve terminal for resynthesis of acetylcholine
48
Q
What is myasthenia gravis?
A
- Acquired, autoimmune disease characterized by fluctuating muscle weakness -> cause by Ab’s that bind and destroy muscle Ach receptors
1. Pts devo muscle fatigue that causes muscles to become weaker during exercise, repetitive activity (typically weaker at end of day)
2. Pts freq have droopy eyelids (ptosis) that INC w/sustained upward gaze; may also have double vision, proximal limb weakness, and may devo difficulty swallowing and breathing - Pts usually respond to AchE drugs, thymectomy, and immunotherapy
- Attached figure shows how the antibodies block the attachment of acetylcholine to its receptors
49
Q
What do you see here?
A
- Myasthenic pt with increased ptosis after sustained upward gaze (bottom)
-
50
Q
What do these images show?
A
- Before upward gaze
- INC ptosis w/sustained upward gaze
- Ptosis reversal post-endrophonium test
- Edrophonium (Tensilon) is a short acting AchE drug that produces a rapid improvement of myasthenic weakness
51
Q
What does this figure show?
A
- Features of compound mm action potential during slow (left) and fast (right) stimulation rates
- Bottom: recordings in a normal individual; potentials do NOT change in amplitude or shape at slow and fast stimulations
- Middle: recordings from pts w/botulism or EL (presynaptic) -> potentials are small, and may get smaller w/slow stimulation rates, but there is a large increment in their amplitude in fast stimulations
-
Top: MG -> amplitude of AP’s get smaller at slow stimulation rates, and during fast stimulations for a while, then there may be a small increment and a late reduction in amplitude; any increments are mild and not as larges as in presynaptic disorders
1. In MG, the test could be repeated after exercise making decremental response more pronounced
53
Q
What is Lambert-Eaton syndrome?
A
- CXR: lung tumor seen in most, but not all patients
- Ab’s block release of Ach by blocking presynaptic voltage-gated Ca channels; impair release of Ach
- Pts have difficulty climbing stairs and DEC salivary production (Ab’s affect not only NM transmission (nicotinic), but also the autonomic ganglia synaptic (muscarinic) receptors)
1. In contrast, MG Ab’s only affect neuromuscular transmission (nicotinic) - Characteristic depressed reflexes (bottom right image) -> muscle stretch reflex may actually improve during few repetitive taps
