Neuromuscular Disease Part 1 - Cartwright Flashcards
Any disease or condition that affects the peripheral nervous system is called a ___ ___ disease
- Anterior horn cell (_____opathy, ___ neuron disease)
- Dorsal root ganglia (____opathy)
- Nerve root (____opathy)
- Nerve plexus (brachial, lumbosacral) –> ___opathy
- Entire nerve (____opathy)
- Neuromuscular junction
- Muscle
Any disease or condition that affects the peripheral nervous system is called a neuromuscular disease
- Anterior horn cell (neuronopathy, motor neuron disease)
- Dorsal root ganglia (neuronopathy)
- Nerve root (radiculopathy)
- Nerve plexus (brachial, lumbosacral) –> plexopathy
- Entire nerve (polyneuropathy)
- Neuromuscular junction
- Muscle
Amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), poliomyelitis are all example of what kind of diease?
motor neuron disease –> neuronapathies
ALS – average age on onset is ____.
It has an unknown cause, ____ and _____ motor neurons die.
Examination is unique because there are ___ AND ___ motor neuron signs.
It causes extremity weakness and affects cranial nerves, no ____ involvement.
___ (____ inhibitor) is only treatment and slows disease by 3 months. Patients die from respiratory failure in 4 years from disease onset.
ALS – average age on onset is 65 years old.
It has an unknown cause where CNS and PNS motor neurons die.
Examination is unique because there are UMN AND LMN motor neuron signs.
It causes extremity weakness and affects cranial nerves, no SENSORY involvement.
Rilazole (glutamate inhibitor) is only treatment and slows disease by 3 months. Patients die from respiratory failure in 4 years from disease onset.
SMA – is autosomal ______ (_____ motor neuron 1 gene mutation) disease.
Type I (__-___) is most severe and affects infants. Give’s “floppy-baby” like symptoms.
Type II, III - childhood onset, but patients can live up to 30 years old with weakness.
Type IV is the most ___. In type IV, ___ ___ cells die off for unknown reasons. Type IV SMA is a common cause of a __tonic infant. There is no treatment. With most severe forms, children die before age 1.
Explain this “new treatment” for SMA.
However, there is a new treatment: Exon skipping therapy called _____. It is approved for SMA 1, 2, 3, 4. It is given every four months. You need a lumbar puncture to inject it into ___ cells.
SMA – is autosomal recessive (Survival motor neuron 1 gene mutation) disease.
Type I (Werdnig-Hoffman) is most severe and affects infants. Give’s “floppy-baby” like symptoms.
Type II, III - childhood onset, but patients can live up to 30 years old with weakness.
Type IV is the most mild. In type IV, Anterior horn cells die off for unknown reasons. Type IV SMA is a common cause of a hypotonic infant. There is no treatment. With most severe forms, children die before age 1.
However, there is a new treatment: Exon skipping therapy called spinraza. It is approved for SMA 1, 2, 3, 4. It is given every four months. You need a lumbar puncture to inject it into thecal cells.
Polio is a ___opathy. It is a disease of the ___ horn cells.
It is a __ __ infection that kills off ___ horn cells. This causes focal ___ motor neuron dysfunction (weakness and atrophy). Often times, it causes ___ weakness and it is asymmetric.
It is a very ___ disease. Older patients may still have affects from a childhood infection (____ leg).
Polio is a neuronopathy. It is a disease of the anterior horn cells.
It is a respiratory viral infection that kills off anterior horn cells. This causes focal lower motor neuron dysfunction (weakness and atrophy). Often times, it causes leg weakness and it is asymmetric.
It is a very rare disease. Older patients may still have affects from a childhood infection (atrophic leg).
How do you tell the difference between ALS and SMA?
In ALS, if you tapped on a tendon, the patients would be hyperreflexic because their upper motor neurons are affected (LS part of ALS…lateral corticospinal). In SMA, they have the amytrophic part, so they are very weak but they don’t have hyperreflexia.
ALS stands for what?
Amyotrophic Lateral Sclerosis
Amyotrophic - anterior horn cell disease (hypotonia)
Lateral Sclerosis - problem with lateral corticospinal tract (hyperreflexia)
Radiculopathy:
Most often from ____ causes (____ disc, ___ spurs) and affects ___ and ____ or ___ discs.
These are treated ____ (discectomy, laminectomy)
Polyradiculopathy:
Damage of multiple nerve roots. This can be from mechanical causes, bad arthritis or pathology in the ___ fluid (infection or cancer)
Radiculopathy:
Most often from mechanical causes (herniated disc, bone spurs) and affects C7, L5 or S1 discs.
These are treated surgically (discectomy, laminectomy)
Polyradiculopathy:
Damage of multiple nerve roots. This can be from mechanical causes, bad arthritis or pathology in the spinal fluid (caused by viral infection or cancer)
Plexopathies are diseases/conditions of the:
- ____ plexus
- ____ plexus
Disease of ___ plexus occurs from:
- ____ trauma – ___/___ and upper trunk
- Motor cycle accident – ___/___ and lower trunk
Brachial and lumbosacral plexopathy both can be caused by ____, ___ and ___-___, and ___.
Plexopathies are diseases/conditions of the:
- Brachial plexus
- Lumbosacral plexus
Disease of brachial plexus occurs from:
- Birth trauma – C5/C6 and upper trunk
- Motor cycle accident – C8/T1 and lower trunk
Brachial and lumbosacral plexopathy both can also be caused by metstasis, infection and post-infection, and diabetes.
Polyneuropathy is a condition of the ___. The damage is distal and symmetric. You can break up polyneuropathy in two different groups:
- ___ (Charcot-Marie-Tooth disease)
- ___
Which one is more common?
You can further break them into two groups:
- ___
- __
Which one is more common?
If you want to find out if you have axonal damage or demylination damage, it is usually determined by ___ ___ studies and ____. It is rarely determined by ___. Axonal will show a lost ____. Demyelination will show a slower ___.
•Demyelinating polyneuropathy is rare – nerve biopsy of demyelinating polyneuropathy shows “__ __” because you myelinate, demyelinate, myelinate, demyelinate
Both types cause a “ ___-____” distribution of symptoms (numbness, tingling)
Polyneuropathy is a condition of the nerves. The damage is distal and symmetric. You can break up polyneuropathy in two different groups:
- Inherited (Charcot-Marie-Tooth disease)
- Acquired
Which one is more common? –> acquired
You can further break them into two groups:
- Axonal
- Demyelinating
Which one is more common? –> Axonal
If you want to find out if you have axonal damage or demylination damage, it is usually determined by nerve conduction studies and EMG. It is rarely determined by biopsy. Axonal neuropatyh will show a loss of amplitude. Demyelination will show a slower velocity.
•Demyelinating polyneuropathy is rare – nerve biopsy of demyelinating polyneuropathy shows “onion-bulb” because you myelinate, demyelinate, myelinate, demyelinate
Both types cause a “stocking-glove” distribution of symptoms (numbness, tingling)
What is going on here?
Demyelination in a polyneuropathy
Your patient comes with a foot with high arches and hammer toes. What is your diagnoses?
This is caused from long-standing neuropathy which causes high arches and hammer toes.
Usually, this is associated with Charcot-Marie Tooth (Inherited Polyneuropathy) because the patient has had it all their life.
Other characteristics of having this disease is having thin lower extremities (stork legs or inverted coke bottle legs). Some diabetics have this (diabetic neuropathy)
There are hundreds of causes of acquired polyneuropathy.
- Axonal (loss of ___ in EMG )
- Demyelinatnig (slow ____ in EMG, “onion-bulb”)
In acquired axonal PN, the most common and important (treatable) axonal PN are caused by:
- _____ – extremely common, 50% of all diabetics, increases risk of amputation, pain can be treated with __ ____
- _____ deficiency
- ___, ____, and ___ (chemotherapy)
Acquired demyelinating polyneuropathy is rare but important to know because it can be life-threatening and is treatable.
Acquired demyelinating PN comes in two flavors:
- Acute – Guillain-Barre syndrome (also called acute inflammatory demyelinating polyneuropathy (AIDP)). This is caused by a ___ or ____ infection, can cause complete ___, and ___flexia, treated with____ or ____ (not ____!)
- Chronic – ______ (presents over months..not as severe)
There are hundreds of causes of acquired polyneuropathy.
- Axonal (loss of amplitude in EMG )
- Demyelinatnig (slow velocity in EMG, “onion-bulb”)
In acquired axonal PN, the most common and important (treatable) axonal PN are caused by:
- Diabetes – extremely common, 50% of all diabetics, increases risk of amputation, pain can be treated with tricyclic anti-depressants.
- B12 deficiency
- Toxins, alcohol and drugs (chemotherapy)
Acquired demyelinating polyneuropathy is rare but important to know because it can be life-threatening and is treatable.
Acquired demyelinating PN comes in two flavors:
- Acute – Guillain-Barre syndrome (also called acute inflammatory demyelinating polyneuropathy (AIDP). This is caused by a GI or respiratory infection, can cause complete paralysis, and areflexia, treated with IVIG or plasmapharesis (not steroids!)
- Chronic – CPID
How do you diagnose Guillain-Barre or AIDP?
Clinical Diagnoses: spinal tap in ER. If a person has AIDP, they will have high protein and normal cell count in their CSF (cytoalbuminologic dissociation).
If you get meningitis or encephalitis and you do a lumbar puncture, you will see high content of white cells as well as protein protein. In AIDP, protein goes up, but cells count is zero.
___ diseases disrupt the connection between the motor neuron and the muscle, within the neuromuscular junction, causes _____ weakness in the ___ and ____, without any ____ involvement
The most common disease in this category is ___ ___. __-___myasthenic syndrome and ____ are two other conditions that affect the neuromuscular junction. Both are __-___ diseases
NMJ diseases disrupt the connection between the motor neuron and the muscle, within the neuromuscular junction, causes alternating weakness in the face and extremeties, without any sensory involvement
The most common disease in this category is Myestinia Gravis. Lambert-Eaton Myasthenia syndrome and botulism are two other conditions that affect the neuromuscular junction. Both are pre-synaptic diseases
The motor unit: a ___ neuron and all the __ __ it innervates
The motor unit: a motor neuron and all the muscle fibers it innervates
- Electrical impulse (action potential) propagates to the pre-synaptic terminal
- Voltage-gated calcium channels are triggered to open up, allowing an influx of calcium into the pre-synaptic terminal
- Calcium interacts with vesicles filled with acetylcholine and they fuse with the pre-synaptic terminal via SNARE proteins, releasing acetylcholine into the cleft through exocytosis
- Acetylcholine binds to post-synaptic receptors on the muscle, causing a sodium influx into the muscle and a potassium efflux out of muscle
- These nicotinic acetylcholine receptors are also called ligand-gated sodium channels
- This results in an action potential in the muscle, which propagates along the sarcolemma
- Acetylcholine diffuses out of the cleft and some is broken down by acetylcholinesterase into acetate and choline
- Choline is taken back up by the pre-synaptic terminal and joins with acetyl-CoA to form more acetylcholine
- Electrical impulse (action potential) propagates to the pre-synaptic terminal
- Voltage-gated calcium channels are triggered to open up, allowing an influx of calcium into the pre-synaptic terminal
- Calcium interacts with vesicles filled with acetylcholine and they fuse with the pre-synaptic terminal via SNARE proteins, releasing acetylcholine into the cleft through exocytosis
- Acetylcholine binds to post-synaptic receptors on the muscle, causing a sodium influx into the muscle and a potassium efflux out of muscle
- These nicotinic acetylcholine receptors are also called ligand-gated sodium channels
- This results in an action potential in the muscle, which propagates along the sarcolemma
- Acetylcholine diffuses out of the cleft and some is broken down by acetylcholinesterase into acetate and choline
- Choline is taken back up by the pre-synaptic terminal and joins with acetyl-CoA to form more acetylcholine
Drug Action in NMJ:
Botulinum toxin:
•Most ___ neurotoxin
___ chains, heavy and light
- ___ chain binds to pre-synaptic terminal and is ____
- The ____ chain cleaves _____ proteins (___ 25 protein, specifically)
- This prevents _____-filled vesicles from fusing and prevents ___ and release of acetylcholine
Drug Action of Botulinum toxin in NMJ:
•Most potent neurotoxin
•Two chains, heavy and light
- Heavy chain binds to pre-synaptic terminal and is internalized
- The light chain cleaves SNARE proteins (SNAP 25 protein, specifically)
- This prevents acetylcholine-filled vesicles from fusing and prevents exocytosis and release of acetylcholine
https://www.youtube.com/watch?v=NZZ9fI3U4k0
(Autoimmune) myasthenia gravis is a disease of the ___:
- Bimodal distribution – affects young ____, older ____.
- Classic ___ disease, can cross ____
- Production of a ____-synaptic _____ receptor ___
- Long-term the post-synaptic membrane becomes _____ (less ____)
- This causes fewer available ____ receptors so there is less ability to cause __ __.
(Autoimmune) myasthenia gravis treatments (4):
- ____ – works quickly, can cause cramps and upset stomach (like a band-aid)
- ____ – for myasthenic crisis (if you can’t swallow, or breath on your own, use these)
- ____ – long course of action (take out someone’s thymus gland. This procedure is reserved for those with severe disease).
- ____ ____ – mainstay of treatment (oral, immune supressing pill). Usually give _____ first, other options include ___ and ___.
(Autoimmune) myasthenia gravis is a disease of the NMJ.
- Bimodal distribution – affects young women, older men.
- Classic autoimmune disease, can cross placenta
- Production of a post-synaptic acetylcholine receptor antibody
- Long-term the post-synaptic membrane becomes smoother (less complex)
- This causes fewer available acetylcholine receptors so there is less ability to cause muscle contraction.
(Autoimmune) myasthenia gravis treatments (4):
- Acetylcholinesterase inhibitors (pyrostigmine) – works quickly, can cause cramps and upset stomach
- IVIG or PLEx – for myasthenic crisis
- Thymectomy – long course of action, reserved for those with severe disease
- Immune suppressants – mainstay of treatment, usually prednisone first, other options include azathioprine, mycophenolate
__-___ Myasthenic Syndrome is a disease of the __:
- It is usually ___ (this means you have a small cell lung cancer that is producing voltage-gated calcium channel antibodies. These anti-bodies bind to the calcium channels of the ___-___ neuron somewhere else.)
- Can be autoimmune
- Weakness may improve with ____
- Typically have dry ___ (why?) and ___ (why?) at patella
Sometimes a patient can come in with LEMS that could be caused by a small cell lung cancer. The cancer produces antibodies against the pre-synaptic voltage-gated calcium channels. This is called paraneoplastic. So, the patient might not know they have cancer, and it is your job to investigate!
•Patient will also have a suppressed and modulated ___ ___.
Lambert-Eaton Myasthenic Syndrome is a disease of the NMJ:
- It is usually paraneoplastic (this means you have a small cell lung cancer that is producing voltage-gated calcium channel antibodies. These anti-bodies bind to the calcium channels of the pre-synaptic neuron somewhere else.)
- Can be autoimmune
- Weakness may improve with exercise
- Typically have dry mouth (why?) and areflexia (why?) at patella. The calcium channel antibodies prevent the release of acetylcholine from all types of neurons, including autonomic neurons. Acetylcholine receptor antibodies only block the receptors on muscles.
Sometimes a patient can come in with LEMS that could be caused by a small cell lung cancer. The cancer produces antibodies against the pre-synaptic voltage-gated calcium channels. This is called paraneoplastic. So, the patient might not know they have cancer, and it is your job to investigate!
•Patient will also have a suppressed and modulated immune system.
