Non-Inflammatory Myopathies - General Information Flashcards
Differentiate a motor neuron disease from a peripheral neuropathy.
Motor Neuron Disease affect cells of the anterior horn (motor neurons) and motor axons and the muscle fibers innervated by them are also affected.
• eg Spinal muscular atrophy, amyotrophic lateral sclerosis
Peripheral neruopathies affect all kinds of neurons (motor, proprioceptive, autonomic, sensory fibers) - so you get both sensory and autonomic problems
Differentiate disorders of neuromusclar transmission from myopathies.
Disorders of Neuromuscular transmission occur as a result of pathology at the neuromusclar junction
Myopaties are due to a primary problem in the muscle
What is the most common symptom of neuromusclar disease?
• what is Gower’s Sign?
• what about winging?
Weakness is the most common symptom, specifically is CENTRAL muscular weakness
*Note the Gower’s sign is due to central musclar weakness in the hips where patients are unable to rise off of the floor*
What has caused this appearance?
Muscle atrophy due to polyneuropathy is shown here
What is happeing here as this lady has maintained a upward gaze?
• what disease is this characterisitc of?
Characteristic of Myasthenia Gravis - she has severe ptosis as here acetylcholine is unable to outcompete antibodies for Nm receptors
Comment on the following aspects of Motor neuron Disease:
• Pattern of Weakness
• Fasciculations
• Muscle Stretch Reflexes
• Sensory Loss
In motor neuron disease the pattern of weakness is variable and often asymmetric in ALS. Muscle fasiculations are seen commonly but reflexes are variable and are most often decreased, but are increased in ALS. There is no sensory loss in this disease.
Comment on the following aspects of Polyneuropathy:
• Pattern of Weakness
• Fasciculations
• Muscle Stretch Reflexes
• Sensory Loss
In polyneuropathy distal weakness is more diminshed than proximal weakness. Fasciculations are seen sometimes and muscle reflexes are decreased or completely absent. Sensory loss is usually present in these diseases.
Comment on the following aspects of Neuromuscular Junction Diseases:
• Pattern of Weakness
• Fasciculations
• Muscle Stretch Reflexes
• Sensory Loss
In NMJ diseases, proximal weakness is often worse than distal weakness and no fasciculations are seen. In postsynaptic disorders like myasthenia gravis reflexes are normal. However, in Lambert Eaton and Botulism they are decreased. No sensory loss is associated with diseases of the NMJ.
Comment on the following aspects of Myopathies:
• Pattern of Weakness
• Fasciculations
• Muscle Stretch Reflexes
• Sensory Loss
In myopathies proximal weakness is typically greater than distal weakness with NO fasiculations. Muscle stretch reflexes will be normal intitially but may become diminished later on. No sensory loss as one might expect.
What are MUAPs and what is their use?
MUAPs - Motor Unit Action Potentials => summation of action potentials transmitted to all the fibers in a motor unit by a single neuron
The size and numbers of MUAPs is very important in neuromuscular disease
Note: shown here is an ATPase stain on muscle. You can see a checkerboard pattern of Type I (light) and II (dark) muscle fibers. While these fibers a intermingled in most tissues a single motor unit is responsible for firing only one fiber type.
What is shown here?
• is it physiologic or pathologic?
• How do you know?
This is muscle that has been injured. Notice the fibers stain dark with most stains and are atrophic and angulated.
**Compare to viable muscle shown below**
What is shown here?
• Normal or Abnormal?
• What causes this?
• What would action potentials look like if detected by an electrode?
Shown here is reorganization of muscle tissue into blocks following reinnervation of muscle tissue. The resultant actions potentials to this tissue will be larger and less frequent than action potential sent to checkerboard tissue.
**Diagram below shows how the innervation has changed**
What is shown here?
• what do dead fibers show up as on EMG?
This just shows atrophic musclar fibers (triangles) that are atrophic due to damage to the motor neuron itself or its axon. These dead fibers produce FIBRILLATIONS on EMG. Once the fibers are reinnervated and revitalized, the action potential becomes much larger.
What is shown here?
• what happens to the number and size of action potentials?
• What other abnormalities are seen in the AP?
Myopathy is shown. Here there will be a normal NUMBER of action potentials occuring on EMG because the number of MOTOR UNITS IS NORMAL. However, fibers within those units are defective so you will is **SIZE REDUCTION in action potentials.
APs are POLYPHASIC**
due to Asynchronous fiber firing
What is the first lab you should get on the serum of someone with a suscpected myopathy?
Creatine Kinase is very often people with myopathies due to muscle cell necrosis and release of contents into the serum
This shows how we measure conduction velocity and the reduction in conduction velocity and action potential amplitude with demyelination of neurons.
What is proximal and distal latency?
• how do we measure this?
Measure how long it takes an electrical impulse to travel down a nerve using two electrodes set at two different locations along the same nerve. We can then look at the difference in travel times down the neuron from proximal and distal locations.
(Distal really shouldn’t be that different than proximal if the axon is properly insulated)
What would you expect the findings to be with regard to the following with Motor Neuron/Anterior Horn Cell Disease?
• Serum Muscle Enzymes
• Nerve Conduction Studies
• Electromyography
• Repetitive Nerve Stimulation Test
• Muscle Biopsy
Serum enzyme levels in these people with motor neuron deficit will be normal or mildly elevated with normal conduction. There will be evidence of denervation (angular cells and atrophy) and reinnervation (fiber grouping). Usually repetitive nerve stimulation is normal (sometimes decreased)
What would you expect the findings to be with regard to the following with Peripheral Neuropathy?
• Serum Muscle Enzymes
• Nerve Conduction Studies
• Electromyography
• Repetitive Nerve Stimulation Test
• Muscle Biopsy
Typically CK levels in people with peripheraly neuropathy is normal, but Conduction Velocity will be LOW or compound motor APs or sensory nerve APs will be LOW. Motor units will be decreased in this disease with evidence of denervation (atrophy, angulation) and reinnervation (blocking). Repetitive stimulation will be normal.
What would you expect the findings to be with regard to the following with myopathy?
• Serum Muscle Enzymes
• Nerve Conduction Studies
• Electromyography
• Repetitive Nerve Stimulation Test
• Muscle Biopsy
With Myopathy CK levels will be ELEVATED and all nerve conduction studies and repetitive stimulation will be normal. There well be polyphasic stimulation on EMG with a normal NUMBER of potentials with a reduction in amplitude. Muscle biopsy will show necrosis or inflammation.
What would you expect the findings to be with regard to the following with neuromuscular transmission defects?
• Serum Muscle Enzymes
• Nerve Conduction Studies
• Electromyography
• Repetitive Nerve Stimulation Test
• Muscle Biopsy
In a transmission defect the CK levels in the serum will be NORMAL with NORMAL nerve conduction studies (no problems intrinsic to the neuron here). EMG will show normal or small motor units with variability of MUAPs (motor unit action potentials). With repetitive nerve stimulation there will be a decrease in the amplitude of CAMPs (compound muscle action potentials) with postsynaptic disorders and an increase with presynaptic disorders. Muscle biopsy will be normal or type II fiber atrophy.
What are the most typical finding in myopathies with regard to:
• Is weakness proximal or distal?
• Sensation?
• Reflexes?
• Muscle enzymes?
Weakness is typically proximal with sensation and reflexes both being in tact.
Notice the different proteins involved in muscle contraction
What key characteristics are seen in this child with DMD?
• what would you expect to see on biopsy?
DMD Child has WINGED scapulae and lordosis (signs of proximal weakness), Calf pseudohypertrophy (hallmark of DMD).
On muscle biospsy you expect necrotic and regenerating fibers to be present. There is also CT between fibers. The Bluish fibers with prominent nuclei are regenerating fibers. Fiber with yellow arrow is undergoing phagocytosis.
(Normal muscle shown on left for comparison)
What is being displayed here?
Dystrophin stain that stains strongly between NORMAL muscle cells, but is completely absent in DMD.
Why does muscle become atrophied in DMD?
Absence of dystrophin causes a secondary excessive entry of calcium into the cell which activates a neutral protease that digests troponin, Z-bands, and Structural proteins causing muscle atrophy.
Are lordosis and calf pseudohypertrophy features of Becker’s muscular dystrophy.
Yes, see patient below
Notice there is still presence of some dystrophin in Becker’s musclar dystrophy.
How are MYOTONIC dystrophies inherited?
• how does this disease manifest?
Autosomal Dominant
What effect is shown in the mother with myotonic dystrophy and her two sons?
ANTICIPATION - disease gets worse with successive generations
What causes McArdle disease?
• what crude test indicates the presence of this disease?
Defective phosphoylase needed to release Glucose 1-phosphate from glycogen
• If you cut of blood supply to a part of this person’s body and measure there lactate you’ll see that it doesn’t increase by much because they can’t lyse glycogen to make glucose that would be used for substrate level phosphorylation
Phosphorylase Staining in a patient with McArdle’s Disease
These patients will also have accumulation of Glycogen within cells because they break it down
What type of neuromuscular syndrome is being shown in the middle here?
This is a Myasthenic Syndrome like Botulism or Lambert Eaton Syndrome. On the left you can see slow muscle stimulation leads to decrements in the maginitude with each stimulation. However, during fast muscle stimulation the magnitude of each contraction actually builds. (this is a key finding)
Compare these findings to a non-pathologic neuromusclar junction
What is shown on the top row here?
• what could we do to make this patient’s syndrome more pronounced in this test?
Myasthenia Gravis (post-synaptic disorder) is shown on the top. You can see that the force of contraction decreases with each action potential in both fast and slow stimulation • This effect will be more pronounced if you test the patient after excercise.
***Note: you sometimes see a increment in fast potential stimulation, but this is mild compared to what is seen in the post-synaptic disorders***
What are some symptoms of Lambert-Eaton Syndrome?
What are some signs of Lambert-Eaton Syndrome?
