Disorders of Neuromuscular Function - Muscle & Nerve Disease Flashcards
describe how an upper motor neuron triggers muscle activity?
Motor system starts with nucleus of upper motor neurons in frontal cortex - motor cortex of frontal lobe -precentral gyrus, those neurons send their acons down through the white matter tracts amd they synapse with anterior horn cells
anterior horn cells can be in the brain stem if they’re part of a cranial nerve that has motor function such as the facial nerve,
or they can be in the spinal cord where they’ll supply nerves to the arms, legs and trunk.
So those anterior horn cells then send their lower motor neurone axons down through the
peripheral nerves and they will end at a synaptic cleft and synapse onto the muscle.
And at that cleft, they release acetylcholine,
the acetylcholine crosses over and binds to acetylcholine receptors on the muscle, and that triggers muscle activity.
what contracts to shorten muscle?
myosin fibrils down here - makes up the bulk of the contractile mechanism.
But if you just shorten those myosin fibrils and they are not attached to the cell membrane,
you won’t actually shorten the whole cell and shorten the muscle. So there needs to be a whole system of proteins,
structural proteins shown here, which bind that myosin to the cell membrane so that when the myosin contracts,
it pulls the muscle membrane with it and shortens the whole muscle membrane.
And those are what we call the structural components.
And then on top of that, you need a mechanism by which the nerve stimulus can initiate all of this process And that’s done through what we call excitation-contraction coupling.
And to do that, you have ion channels. And when the nerve signals to the muscle,
it opens or closes ion channels and therefore you get a release into the cell or out of the cell of various electrolytes,
including sodium, potassium, calcium and chlorine down specific channels.
And that sets off the contractile mechanism. And to do all of that, you need energy.
And the energy in muscle cells primarily comes from the breakdown of glycogen and fatty acids, which generate ATP, which drives this whole process.
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And that’s all done particularly by mmitochondria
what are symptoms of muscle disease?
Weakness of skeletal muscle
Respiratory and swallowing muscles important
Cardiac symptoms (cardiomyopathy, arrhythmias)
Cramps/muscle pain, stiffness
Myoglobinuria (muscle breakdown product in urine)
what are symptoms of muscle disease in babies?
floppy, poor suck / feeding / failure to thrive
do you get sensory signs in muscle disease?
no purely motor features
what investigations do you do for muscle disease?
History and examination
Bloods esp creatine kinase (CK)
Electromyography (EMG)
Muscle biopsy
Structure, biochemistry, inflammation
Genetic testing
what are congenital / genetic causes of muscle disease?
Contractile: congenital myopathies
Structural: muscular dystrophies
Coupling: channelopathies
Energy: metabolic myopathies
what are aquired causes of muscle disease?
Electrolyte disturbance (esp K+)
Endocrine (thyroid, adrenal, vitamin D)
Autoimmune inflammatory muscle disease
Iatrogenic: medication (steroids / statins)
what is inflammatory muscle disease?
group of rare diseases that involve chronic (long-standing) muscle inflammation, muscle weakness, and in some cases, muscle pain
autoimmune
affects any age
what is Polymyositis?
Polymyositis is a disease that causes muscles to become irritated and inflamed. The muscles eventually start to break down and become weak.
what is dermatomyositis?
Dermatomyositis is a rare disease that causes muscle inflammation and skin rash. It’s one of a group of muscle diseases that cause muscle inflammation and swelling. It’s different from other muscle diseases because it also causes skin problems.
what are symptoms of inflammatory muscle disease?
Acute or subacute, painful, weak muscles
Characteristic rash of DM
what are investigation findings for inflammatory muscle disease?
High CK, autoantibodies, tumour screen (esp DM)
EMG & biopsy
what is treatment for inflammatory muscle disease?
immunosuppression
what is the role of cholinesterase in neuromuscular junction?
breaks down acetylcholine - you have that enzyme in the synaptic cleft is you don’t want acetylcholine just accumulating
what is myasthenia gravis?
So it’s another autoimmune condition. And this antibody would block the acetylcholine receptor and therefore stop the
acetylcholine from activating the receptor and generating muscle contraction.
what is clinical presentation of myasthenia gravis?
fatigue
Ocular: eyelids (ptosis)
muscles of eye movement (diplopia)
Generalised: limbs
bulbar (chew, swallow, talk) breathing
what investigations are done for myasthenia gravis?
ACh receptor or anti-MuSK antibodies
Neurophysiology
CT chest (thymoma)
what is treatment for symptomatic myasthenia gravis?
cholinesterase inhibitors
what are disease modifying treatments for myasthenia gravis?
immunoglobulin /
plasma exchange
steroids
steroids sparing immunosuppression
thymectomy
what does the peripheral nerve consist of?
Axons
Sensory: small fibres (pain + temperature)
large fibres (joint position sense + vibration)
Motor
Autonomic
Nerve sheath (myelin)
what are causes of peripheral nerve disease?
Root disease
Commonly degenerative disc disease
Lesion of individual peripheral nerve
Compressive / entrapment neuropathy
Vasculitic (mononeuritis multiplex)
Generalised peripheral neuropathy
Motor / sensory / both
+/- autonomic features
what are causes of Generalised peripheral neuropathy?
Hereditary
Metabolic: diabetes, alcohol, renal failure, vitamin deficiency
Toxic: drugs
Infectious: Lyme, HIV, (leprosy)
Malignancy: paraneoplastic
Inflammatory (autoimmune), usually demyelinating:
Acute = Guillain Barre syndrome (post-infectious)
Chronic = chronic inflammatory demyelinating polyneuropathy
what are symptoms of peripheral nerve disease?
Sensory:
Loss of sensation, abnormal sensation, pain
Motor:
Muscle thinning, weakness
Autonomic
Skin changes, blood pressure, bowel, bladder
what are signs of peripheral nerve disease?
Sensory
Motor
lower motor neuron
Distribution
Root (myotome / dermatome)
Single nerve
Generalised nerve: distal first
what are investigations for peripheral nerve disease?
Blood tests
Nerve Conduction Studies / electromyography
Lumbar puncture (CSF analysis)
Nerve biopsy (nb sensory nerve)
Genetic analysis
what is the treatment for peripheral nerve disease?
Treat the cause eg stop drug, surgery, immunoglobulin
what is anterior horn cell disease?
let’s move on to anterior horn cell disease. So, most problems that affect the anterior horn cells also actually affect the upper motor neuron.
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So you have involvement both the upper motor neuron and the anterior horn cell and lower motor neuron.
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There are rare conditions that just caused a generation of the anterior horn cell, and those are conditions called spinal muscular atrophies.
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And they’re pretty rare, tend to present in childhood. Usually genetic.
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But for our purposes, we are going to look at the most common condition that affects the anterior horn cell.
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And that’s one that also affects the upper motor neuron. And that’s motor neuron disease.
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And it’s perhaps a little surprising that over the years, quite a few famous celebrities have had motor neuron disease.
what is motor neuron disease
Usually limb → bulbar → respiratory
combination of upper and lower motor neuron signs
LMN = muscle fasciculations, wasting, weakness
UMN = spasticity, brisk reflexes, extensor plantars
No sensory involvement
10%+ have cognitive decline
what is the prognosis for motor neuron disease?
Median 3-5 years from symptom onset, 2-3 years from diagnosis
50% die within 14 months of diagnosis
how is motor neuron disease diagnosed?
Clinical : unique combination UMN + LMN signs, no sensory signs
Electromyography
(Genetics)
how is motor neurons disease treated?
Supportive: Physio, OT, SALT, PEG feed, non-invasive ventilation, care
Riluzole (glutamate antagonist)
Anticipatory / palliative care
