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Question 1

What NM diseases are caused by damage to theanterior horn cells or motor neurons?

Answer 1

so called motor neuron diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis (this also affect the upper motor neurons).In these conditions, the motor axonsand the muscle fibers innervated by them are also secondarily affected.

Question 2

What are peripheral neuropathies?

Answer 2

these involve not only motor axons, but also other various types of nerve fibers such as those that carry pain and proprioceptive sensations, and autonomic fibers, so peripheralneuropathies also cause sensory or autonomic problems.

Question 3

What is a commondisease of the neuromuscular junction?

Answer 3

also called disorders of neuromuscular transmission such as myasthenia gravis.

Question 4

The most common symptom of neuromuscular disease is ____

Answer 4

weakness

Question 5

What is Gower’s Sign?

Answer 5

In myopathic disease, weakness primarily affects the proximal muscles. Such patients have difficulty arising from the floor because of hip muscle weakness or raising the arms above their head.In this, because of hip muscle weakness, the patient needs to use his hands to raise from the floor shown in figure 1 and then ”climb over his legs” in figures 2, 3, and 4 (Gower’s sign) to achieve the standing position in figures 5 and 6.

Question 6

What does this image show?

Answer 6

Patients with myopathies also have proximal muscle atrophy and weakness, as is shown in the next patient with shoulder atrophy at arrow 1 and “winging” of the scapula at arrow 2. Winging of the scapula occurs because the weak muscles cannot fix the scapula to the rib cage.

Question 7

What is a characteristicfindingpoly-peripheral neuopathies?

Answer 7

Distal Leg Wasting. These patients typically also have decreased sensation and depressed reflexes

Question 8

Patients with _____________do not have sensory deficits as those disorders affect only the motor axons.

Answer 8

motor neuron diseases

Question 9

What is amononeuropathy?

Answer 9

Neuropathies thataffect individual nerves

Question 10

What is characteristic of a myasthenia gravis (MG) patient following sustained upward gaze?

Answer 10

Ptosis. This is characteristic of myasthenia gravis, a disease of neuromuscular transmission in which muscle fatigue is a hallmark.

Question 11

What would a symmetric pattern of muscle weakness, with fasciculations, decreased muscle stretch relfexes, and no sensory loss suggest?

Answer 11

Motor neuron Disease?

Question 12

What is one motor neuron disease that doesnt present normally?

Answer 12

ALS- still see fasciculations andno sensory loss BUT weakness patterns are asymmetric and muscle stretch reflexes are increased

Question 13

What categories of NMD would present more commonly with distal patterns of weakness over proximal?

Answer 13

Polyneuropathies

Question 14

How do Polyneuropathies present?

Answer 14

distal pattern of weakness, with decreased or absent muscle stretch reflexes, sensory loss and fascicualtions sometimes

Question 15

What are some common characteristics of diseases of neuromuscular junction and myopathies?

Answer 15

both predominantly involve proximal over distal patterns of weakness, and you do NOT see fasciculations or sensory loss

Question 16

What diseases of the neuromuscular junction present with normal muscle stretch reflexes?

Answer 16

POST-synaptic disorders such as myasthenia gravis

Question 17

What diseases of the neuromuscular junction present with decreased muscle stretch reflexes?

Answer 17

Lambert-Eaton myastenic syndrome and botulism

Question 18

Are muscle stretch reflexes present in myopathies?

Answer 18

Normal Initially, may be decreased in later stages (ankle reflexes often preserved until late)

Question 19

What aremotor unit action potentials (MUAPs).

Answer 19

When the motor neuron depolarizes, it causes the muscle fibers of that motor unit to also depolarize and their individual action potentials summate (A+B+C+D) forming the potentials

Question 20

What is electromyography?

Answer 20

A diagnostic toolwhich detects MUAPsclose to a needle electrode inserted in the muscle and connected to an oscilloscope. Analysis of the characteristics of the motor unit action potentials, their size, and numbers is a very important diagnostic tool in neuromuscular disease.

Question 21

What is this?

Answer 21

Normal muscle histology (trichrome stain)

Question 22

What is this showing?

Answer 22

Normal muscle biopsy stained with alkaline ATPase.Note that the type I muscle fibers stain pale while the type II fibers are dark. Fibers of either type are innervated by one type of motor neuron (motor unit). Here, fibers of various motor neurons, either type I or II, are intermixed in an almost checkerboard pattern.

Question 23

T or F.A motor neuron and the fibers that it innervates belong to only one type

Answer 23

T,and the physiological and histological characteristics are determined by the motor neuron and its firing pattern. In humans the checkerboard pattern is seen in most muscles, with some having more of one fiber type depending on the muscle function.

Question 24

Whathappens when a muscle loses it’s innervation through some injury, for example by trauma to its axon,a peripheral neuropathy or damage to the motor neuron?

Answer 24

the muscle fibers become atrophic and angulated.slide: esterase stain

Question 25

What is fiber type grouping?

Answer 25

When axons are damaged there is sprouting of axons from the other intact neurons that take over and reinnervate previously denervated fibers, thus more fibers of single neurons remain, forming groups of both fiber types seen histologically. 

Question 26

How does an EMG change in peripheral nerve injury with fiber type grouping?

Answer 26

The action potentials generated by these will be larger, as more muscle fibers innervated by a single motor neuron will be detected by the needle electrode during muscle contractions using EMG recording. However, the total number of action potentials will be decreased (fewer number of motor neurons). Thus, in peripheral nerve injury with denervation and reinnervation there are fewer, but larger, motor unit action potentials on EMG. 

Question 27

T or F. In myopathies, the muscle fibers are not atrophic and angular. 

Answer 27

T. In this case, they are necrotic (appearing pale here) from an autoimmune myopathy.  In other myopathies, there could be structural abnormalities.

Question 28

Where is the defect in myopathies?

Answer 28

the individual muscle fibers are ill or nonfunctional (thus when a muscle contracts the motor unit action potentials are smaller)

Question 29

T or F. In myopathies, the number of motor units is not decreased, unlike neurogenic disorders

Answer 29

T., because the number of motor neurons or axons are normal.  (It is the number of individual fibers of the motor unit that are nonfunctional or dead). Even when the muscle contraction is very weak, there is a normal number of motor unit action potentials (this might appear increased for a weak muscle). 

Question 30

What are some serum markers of myopathies?

Answer 30

The sick, necrotic muscle fibers leak some of the sarcoplasmic components such as enzymes like creatine kinase (CK or CPK).  Because of this, the enzymes are elevated in serum. 

Question 31

EMG changes in myopathies?

Answer 31

The motor unit action potential is small.This is also polyphasic because the damaged individual fibers fire asynchronously.

Question 32

Motor Conduction Velocity

Answer 32

stimulation of the ulnar nerve at the wrist on left and the elbow on the right with recordings at the adductor digiti quinti muscle.  In the middle, notice the compound muscle action potential (summation of all motor units generated by a maximal nerve stimulation).  One can also observe the latencies and measure the amplitudes.Conduction velocities are calculated by dividing the distance between the two stimulation electrodes by the difference of their latencies = distance/latency 1 – latency, 2 = CV (conduction velocity).In the bottom, notice the very slow prolonged latency and small compound muscle action potential in a demyelinating neuropathy.

Question 33

Serum muscle enzymes are elevated in what kinds of NMD?

Answer 33

mildly in anterior horn disease and elevated in myopaties

Question 34

Nerve conduction studies are only abnormal in what type of NMD?

Answer 34

peripheral neuropathy results in slow conduction

Question 35

How is an EMG changed in anterior horn disease or peripheral neuropathy? 

Answer 35

Decreased number of motor units, evidence of denervation & some reinnervation (large motor units)

Question 36

How does an EMG change in myopathy?

Answer 36

Normal number of motor  units, of short duration & low amplitude & frequently polyphasic

Question 37

Repetitive Nerve stumulation test is abnormal in what type of NMD?

Answer 37

Neuromuscular transduction defects- CMAPs at low rate of stimulation, ,decrease in amplitude, increment at fast rates in presynaptic disorders

Question 38

Classic findings of myopathy?

Answer 38

•Proximal (and usually symmetric) weakness• Normal sensation and reflexes• Elevated muscle enzyme in serum (CK or CPK)•Small (brief) motor unit potentials on EMG, with normal or “increased” recruitment on maximal effort or polyphasic •Abnormal muscle biopsy, depending on the type of myopathy (i.e., inflammation, glycogen storage)

Question 39

T or F. In myopathies, Motor Unit Action Potentials are not decreased in number

Answer 39

T. thus when the muscle contracts, even if weak, many motor units are recruited.  Remember that the reason that the numbers of Motor Units are not reduced (unlike in neuropathies) is because the number of motor neurons and their axons are not reduced, yet they are small because there is a lesser number of functional muscle fibers per unit. 

Question 40

What are the congenital myopathies?

Answer 40

These appear as floppy infants (weakness, hypotonia) at birth; e.g. central core disease,myotubular myopathy,“nemaline” or “rod” myopathy andcongenital muscular dystrophy shown. A Floppy Infant With Infantile Acid Maltase Deficiency

Question 41

What are the muscular dystrophies? When do these initially present?

Answer 41

These are hereditary and progressive conditions and start during childhood or later and eventually cause weakness and atrophy e.g., Duchenne’s, Becker’s,limb girdle, fascioscapulohumeral and oculopharyngeal dystrophies

Question 42

What are the myotonic dystrophies?

Answer 42

Myotonic dystrophies are also hereditary and progressive, but in addition to weakness they also have difficulty relaxing their muscles associated with abnormal electrical activity of muscle.  This difficulty with relaxing the contracted muscle is called myotonia.

Question 43

What is Duchenne's Muscular dystrophy?

Answer 43

An X-linked recessive lethal childhood disorder caused by a gene mutation resulting in lack of the protein, dystrophin

Question 44

How does Duchenne's Muscular dystrophy present?

Answer 44

There is progressive muscle weakness that progresses to necrosis and atrophy of muscle  as well as heart abnroamlities, low IQ, and pseudohypertrophy

Question 45

What is this muscle biopsy showing?

Answer 45

Muscle biopsy of a child with Duchenne’s dystrophy. Note the bluish fibers with a prominent nuclei - they are regenerating fibers. Also there is prominent connective tissue between fibers and one necrotic fiber undergoing phagocytosis (yellow arrow).

Question 46

What is this?

Answer 46

Immunoperoxidase stain for dystrophin – notice the normal staining in the muscle membrane in a control (left), and a very abnormal muscle without dystrophin from a child with Duchenne’s dystrophy (right)

Question 47

How does a lack of dystropin affect muscle?

Answer 47

the absence of dystrophin causes a membrane defect that causes intracellular Ca2+ to rise, Ca2+ activation of neutral proteases that digest troponin and Z-bands and overall degradation of strucural proteins leading to MUSCLE ATROPHY 

Question 48

What is a novel treatment for Duchenne's dystrophy?

Answer 48

Exon skipping to restore the reading frame producing a message that although smaller, makes sense, so this could be a smaller yet functional protein. 

Question 49

How can exon restoring be performed?

Answer 49

injection of a morpholino, which is an antisense oligonucleotide that restores the reading frame (in clinical trials now)

Question 50

What is Becker's Muscular Dystrophy?

Answer 50

milder case similar to Duchenne's Image: Note the lordosis and the calf hypertrophy. 

Question 51

What is this?

Answer 51

muscle biopsy of a Becker’s patient stained for dystrophin.  Notice that several muscle fibers still have the protein, i.e., not an absence as in Duchenne’s dystrophy.

Question 52

What is the MOI of myotonic dystrophies?

Answer 52

AD

Question 53

Myotonic dystrophy

Answer 53

Photograph of a mildly affected female with myotonic dystrophy and her two children who much more affected - note the elongated faces. As in most autosomal dominant diseases there is anticipation with increased repeat expansions and more severe phenotypes in younger generations.

Question 54

What are inflammatory myopathies?

Answer 54

These are acquired diseases mostly autoimmune (polymyositis, dermatomyositis, inclusion body myositis, sarcoidosis) or caused by infections (trichinosis).

Question 55

What are metabolic myopathies?

Answer 55

The metabolic myopathies are caused by enzyme deficiencies that blocks the metabolic pathways, depriving muscle cells of energy for muscle contraction and relaxation and to maintain their membrane integrity.

Question 56

How do metabolic myopathies present?

Answer 56

Some manifest by weakness, but the majority by episodes of muscle pain and breakdown (rhabdomyolysis) and excretion of muscle proteins in the urine (myoglobinuria) when the energy demands increase such as during exercise.

Question 57

What is McArdle’s disease?

Answer 57

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 the lack of normal increase, particularly during ischemic exercise when glycogenolysis is normally utilized as an energy source.

Question 58

What is this?

Answer 58

Biopsy of a patient with McArdle’s disease in center, showing lack of phosphorylase staining (blood vessels but not muscle stain positive, compared with the normal muscle on the left)

Question 59

How do endocrine myopathies present?

Answer 59

Endocrine disorders can cause proximal muscle weakness and their muscle biopsies show non-specific findings and only selective type II muscle fiber atrophy. 

Question 60

What are the causes fo endocrine myopathies?

Answer 60

Cushing's disease and hypothyroidism Hyperparathyroidism might present with severe weakness resembling amyotrophic lateral sclerosis. Hypothyroidism patients present with muscle spasms but not weakness, and could have a very high serum creatine kinase levels, so this should be suspected in obese patients with hyperlipidemia and high serum creatine kinase.

Question 61

Some selective things that cna cause toxic myopathies?

Answer 61

-ethanol-anesthetics like lidocaine-Cholesterol-lowering agents like statins-glucocorticoids

Question 62

What are the disorders of neuromuscular transmission?

Answer 62

Such disorders include acquired diseases like Myasthenia Gravis, disorders caused by toxins such as Botulism, or hereditary diseases such as Congenital Myasthenic Syndromes.

Question 63

How does neuromusuclar transmission occur?

Answer 63

a)The acetylcholine vesicles in the nerve terminal.b)The nerve action potential.c)  The voltage gated calcium channels that open after the arrival of the nerve action potential initiateing acetylcholine release at the neuromuscular junction.e)  The acetylcholine molecules attach to their receptor in the muscle area of the junction, which then triggers the opening of its ionic channel. This produces an end plate potential (EPP).f)   If the EPP is of sufficient magnitude, it causes the opening of the muscle sodium channels. This, in turn, initiates a muscle action potential that propagates and then triggers the mechanism of muscle contraction.  

Question 64

What is a MEPP?

Answer 64

 Spontaneous release of acetylcholine that does not trigger a muscle action potential is called a miniature end plate potential (MEPP).

Question 65

What happens to used Ach?

Answer 65

Acetylcholine is removed  from the synaptic cleft from 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.

Question 66

How can you test the function of the neuromuscular junction, and to diagnose diseases of neuromuscular transmission? 

Answer 66

Nerves are stimulated with a series of stimuli.In normal muscle the compound muscle action potential does not change in amplitude during these several stimuli. In neuromuscular transmission disorders such as myasthenia gravis, the amplitude becomes smaller during slow, repetitive stimulation. In presynaptic disorders the compound action potential becomes larger during fast stimulation rates

Question 67

What is Myasthenia Gravis?

Answer 67

An acquired disease caused by impaired neuromuscular transmission due to blockade of acetylcholine receptors by auto-antibodies characterized by fluctuating muscle weakness that worsens with muscle activity and at the end of the day when patients typically are weaker than in the morning. 

Question 68

Presentation of MG? Classic signs?

Answer 68

Patients frequently have droopy eyelids (ptosis) which increases with sustained upward gaze.  They may also have double vision and proximal limb weakness and may develop difficulty swallowing and breathing.

Question 69

Treatment of MG?

Answer 69

—-Anticholinesterase drugs such as pyridostigmine—-Corticosteroids (suppress Ab production)—-Immunosuppressants (suppress Ab production):   —azathioprine, cyclophosphamide, mycophenolate mofetil—-Thymectomy—-Plasma exchange (removed Abs)—-Immunoglobulin infusions (block Abs)

Question 70

This figure shows the features of the compound muscle action potential during slow (left) and fast (right) stimulation rates.  With fast stimulation rates the recording of the potentials is seen as straight vertical lines because of technical changes in the recordings.On the bottom recordings in a normal individual, the potentials do not change in amplitude or shape at slow and fast stimulations. In the middle are recordings from patients with botulism or Eaton Lambert Syndrome ( presynaptic); the potentials are small, and they may get smaller with slow stimulation rates, but there is a large increment in their amplitude during fast stimulations.  In Myasthenia gravis (top), the amplitude of the action potentials get smaller at slow stimulation rates, and also 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.  In myasthenia, the test could be repeated after exercise which makes the decremental response more pronounced.

Question 71

What is Eaton Lambert Syndrome?

Answer 71

Disease in which antibodies block the release of acetylcholine by blocking the presynaptic voltage gated calcium channels that impair the release of acetylcholine . 

Question 72

Symptoms of ELS (Botulinum)

Answer 72

-lung tumors common (not all)-proximal limb weakness0small and poorly reactive pupils from impaired sympathetics -difficulty with activity or difficulty rising from sitting position-decreased saliva production; metallic taste  

Question 73

Why do you see decreased saliva production in ELS?

Answer 73

Decreased salivation is explained because the antibodies affect not only the neuromuscular transmission (nicotinic), but also affect the autonomic ganglia synaptic (muscarinic) receptors.  In contrast, in Myasthenia Gravis the antibodies only affect neuromuscular transmission (nicotinic). 

Question 74

Signs of ELS?

Answer 74

Proximal limb weakness (legs > arms) Reduced muscle stretch reflexes Transient improvement in muscle power following exercise

Question 75

How is ELS treated?

Answer 75

REMOVAL OF ASSOCIATED NEOPLASM“SYMPTOMATIC “ BOOST OF NEUROMUSCULAR  TRANSMISSION Cholinesterase inhibitors (pyridostigmine)3,4- diaminopyridine (availability)IMMUNOSUPPRESSIVE THERAPY High-dose, long-term corticosteroids Azathioprine Plasmapheresis

Question 76

Ancillary tests:-muscle enzymes were normal-Maximum motor nerve conduction were 30m/sec in the ulnar nerve (normal greater than 50m/sec) and 27m/s in the peroneal nerve (normal greatre than 45 m/sec)-EMG disclosed fibrillations, large and long motor action potentials and recruitmentDX?

Answer 76

Step page gait= when walking patient has to raise the leg and has foot drop 

Question 77

Case 1 continued Fibrillations are signs of denervated muscle due to sensitized receptors to Ach

Answer 77

This is a peripheral neuopathy 

Question 78

Why is he having weakness noted in climbing stairs? 

Answer 78

serum CPK is 350 (elrvated)nerve conduction studies were normal and number of recruited studies were normal and the number of receruited motor units action potentials for the degree of effort were increased on EMG Muscle weakness of the pelvic girdle 

Question 79

In what disease category would 'ragged-red fibers be seen on a muscle biopsy?

Answer 79

mitochondrial disorders

Question 80

serum CK was 25000 IU/L (normal less than 200)Why is the urine dark?

Answer 80

the muscle fiber is damaged here and the dark urine is due to myoglobin in the urine 

Question 81

What will you in muscle biopsy in this patient?

Answer 81

muscle necrosis and phosphorylase deficiency

Question 82

Repetitive nerve stimulation test in myasthenia gravis 

Answer 82

Characteristic of a pre-synaptic disease 

Question 83

How does Botulinum present?

Answer 83

this needs to be in the DDx of ELS (pre-synaptic)patients get areflexia, large pupils, xerostomia