Jun 05, 2023
The skeletal muscles, which our body utilizes to move, become weak due to the neuromuscular condition known as myasthenia gravis. Myasthenia Gravis develops when there is a breakdown in nerve-muscle connection. Myasthenia gravis is the most prevalent primary condition of neuromuscular transmission, according to the Myasthenia Gravis Foundation of America.
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It is a type of two hypersensitivity reactions. It's an autoimmune disorder which will be having a waxing and waning course. It will have exacerbations especially in pregnancy and infection and it could be worsening to a level that the person might require ventilatory support. That's called a Myasthenic crisis. It is also mentioned as type V hypersensitivity reaction, in some books. In myasthenia gravis the basic problem is the receptors for acetylcholine are the ones which are affected, It's a supposed junctional defect. Acetylcholine will act on its receptor having a total of five subunits:
Alpha subunit is of concern because when it is activated, the sodium influx would be occurring subsequently causing a depolarization. There will be firing of the neuromuscular endplate, which allows the muscles to contract. The anti AchR antibody includes the following functions:
The common parameters is that due to all these effects, the efficiency of neuromuscular transmission is affected significantly and it reduces the ability of the muscle to perform.
The above image shows a Repetitive Nerve Stimulation test in which you stimulate a nerve at a lower frequency than at a high frequency. When you stimulate the muscles as they keep on performing, their performance reduces. Usually the performance reduction is less than 10%. A substantial reduction in the performance of the muscle is seen. This is because the nerve is being continuously stimulated. The reason for this is that the acetylcholine is not being able to activate its receptors properly due to various reasons. The technical term is Decremental Response.
Clinical studies have shown that 75% of patients of Myasthenia Gravis are having a thymus abnormality (65% are having a thymic hyperplasia and 10% are having a thymoma). Thymoma is a benign tumor,which can spread locally and it can press on the recurrent laryngeal nerve.
The thymus is having the cells that are called myoid cells as antigens. On the surface of these myoid cells, there is an alloantigen. This is the antigen against which antibodies are formed and the chemical structure of this antigen resembles the acetylcholine receptor. When target receptors are affected, then the functioning of muscles will be affected. Antibodies present are T cell dependent and IgG class which can cross the placenta. If a mother or a young lady has autoimmune disease, she can transfer this antibody to her baby, and congenital myasthenia gravis or neonatal Myasthenia Gravis will be a presentation in this case.
It has a figure of 200 cases for every 100,000 people in Western populations. It is common in young women or in men after 50 to 60 years of age. The disease can be showing an exacerbation it will be having a waxing and a waning course. The exacerbations can be triggered by infection, or by pregnancy. The young female might be fighting for her life at the time of pregnancy when she goes into a myasthenic crisis. During which, there will be a diaphragmatic paralysis developing in a patient.
This picture shows a young lady who's suffering from Myasthenia gravis. She has involuntarily elevated her eyelids to keep her eyes open when she was asked for medical photography. Initially, most patients having Myasthenia Gravis don't realize that they're having ptosis. Persons having ptosis use the forehead muscles to elevate the upper eyelids.
The cornea and the upper two millimeters on the cornea is always covered by the upper eyelid. In patients of Myasthenia Gravis when they wake up in the morning they will not have any ptosis but suppose the patient is watching television news or they are fiddling around with a smartphone, then there will definitely be stress on the eye muscles and that will trigger a ptosis. And when we examine the patient, we will notice that this Ptosis is never symmetrical. It will always be the asymmetrical ptosis developing in a patient.
If this patient has not watched television, then the patient will say that in the morning they are feeling fine but by evening the patient is not sleepy, but still her colleagues are asking her why she looks so sleepy. And if this person is working on a computer in the office, she will have to involuntarily use her forehead muscles to elevate her eyelids to type on the computer. As there is asymmetrical ptosis that explains why there will be a double vision developing in the patient. So in these patients we will request this person to simply do an upward gaze for as little as 30 seconds and there will be a development of symptoms of ptosis and diplopia in the patient. Some patients might be having only the extra ocular muscle weakness as a presentation for the whole of their life . If the symptoms of extra ocular muscle weakness persist for more than three years then the term that is used to describe is called ocular myasthenia gravis. In this case, we should do a CT or an MRI to rule out any CNS cause that can also contribute to ptosis. Here, the problem is not any mass effect of any tumor or aneurysm going in the brain but it is a neuromuscular function at the junction not occurring properly. Now, we have asked this lady to smile which in this case, would be a snarling appearance coming up. So patients of Myasthenia Gravis are set to have Snarling faces which is a feature of myasthenia gravis. They may not be visible initially.
This is based on the fact that when this person is eating non veg food, it is taking longer for the patient to finish the meal . So, pharyngeal muscles, tongue muscles, cannot function normally. So the ability to eat fast and the ability to swallow food fast will not be present in these patients. Chewing muscle is a more prominent muscle weakness which is exaggerated on eating non vegetarian foods especially meat or mutton etc..
If we talk continuously we still have the same voice, pitch. But in these patients because of the weakness of the pharynx, muscles of the throat, there can be development of nasal twang. Especially the weakness of the soft palate.
There can be nasal regurgitation of fluids. When the person drinks water, coke, it might come out of the nose.
Here the aspiration risk will be so high that we will have to admit the patient to the Intensive Care Unit and manage the patient conservatively.
With Dysphagia, it might seem that the esophagus is involved. But esophagus is smooth muscle and this is a disease of the skeletal muscle. Because the tongue cannot perform like a normal person, we are using the word oropharyngeal dysphagia.
In some patients, even muscles related to vocal cords will be affected. There are two reasons why the person is not able to speak properly. One is the Nasal Twang of the voice and The second is dysarthria related to muscles with the vocal cord. We can go on speaking hours without any change in the pitch and quality of the voice. But in these patients, the unclear speech will start developing after continuous speaking for two to three minutes.
The deep tendon reflexes in these patients are preserved. The muscle weakness is prominent in these patients; it increases with activity of the same muscle. There is a diurnal variation of features in these patients. But in spite of all this motor weakness, the reflexes in these patients are preserved unlike Lambert Eaton syndrome. The DTR would be normal in these patients. Sensory function is not affected in these patients so sensation in the throat is preserved. There's no problem with the gag reflex per se.
In this condition there is arm and leg weakness in Myasthenia Gravis. If we ask this person to spread out arms and keep arms abductors up, then we will notice that even shoulder muscle fatigue will start developing and they will be drooping in the arms of the patient. So, muscles of the hip joint muscles of the shoulder joint can be involved but as a late manifestation in the disease. In Lambert Eaton syndrome, the primary complaint will be proximal muscle weakness. So, suppose there is a female, she has long hair. She says when she comb her hair, she feels as if the comb has become heavy. So when she used to do this brushing activity or combing the hair activity that deltoid weakness used to manifest in the person.
This molecule is a short acting anti anticholinesterase agent. If you will give this injection intravenously the onset of action will be after 30 seconds and the maximum duration of this drug is five minutes. We do not push 10 milligrams right away because it can trigger a cholinergic crisis. So first we will give two milligrams which will inhibit the degradation of acetylcholine.
As we are inhibiting the degradation of acetylcholine, it will be able to act on the receptor for longer duration. Most of the time when you give two milligram of edrophonium, there will be a marked improvement in the patient.If there is no improvement, then we can give the remaining eight milligram of edrophonium to the patient and wait for a clinical response. We will look at the ptosis component or we can ask the patient to separate the arms before and after the performance of the test and see how long he can hold the arms in abduction position. So, we have three things :
It is on the backseat or it is not given in the front primarily because of hyper Salivation, hyper lacrimation. There is frequent urination, diarrhea, gastrointestinal complaints, and miosis in patients. During the performance of this test, if we are having a volunteer crisis, Atropine has to be given to the patient.
(Ice Pack test- alternative of Tensilon Test)
There is a man having asymmetrical Ptosis. Now we have taken some ice , rolled it in a glove or maybe a commercialized pack which comes with vaccines, etc. And we put it on the patient and we notice that after applying the ice pack for 3-5 minutes, the Ptosis of the patient has substantially reduced.
The application of ice is contributing to reduction in the symptoms. Acetylcholinesterase is very sensitive to temperature. If we decrease the temperature, then the activity of acetylcholinesterase enzymes tends to reduce. So there is decrease in turnover of receptors and acetylcholinesterase is lesser, acetylcholine will not be broken down and therefore there will be a better action available. The test of the ice pack has a sensitivity equal to that of the tensilon test.
Neonatal Myasthenia Gravis means that the mother of this child was having Myasthenia Gravis and at the time of delivery and before delivery, she has transferred the antibodies to a child.
When it comes to a male patient the association is with aggressive lung cancer that is small cell cancer of the lung. So this can be a paraneoplastic manifestation related to lung cancer. In this, the problem is that the production of acetylcholine is lesser. This is a pre synaptic disease whereas Myasthenia Gravis is a postsynaptic, post junctional disease where the receptors of acetylcholine are defective. This is a presynaptic disease in which the release of acetylcholine is compromised.
Let us assume that this is where the acetylcholine will be released and we have the receptors available.There is production of antibodies when muscle is stimulated. The antibodies which are present here, they go and attack the neuromuscular junction, but they do not attack the receptors. Now the antibodies will act on the pre junctional site and reduce the acetylcholine release because of which we are calling it a pre junctional defect. Therefore, due to less stimulation, the contraction of muscles and this condition will also be relatively less.
You can imagine this to be normal amplitude or contraction for any one. So, nerve stimulation versus Lambert Eaton where the contraction is really poor. Because this contraction is poor, we will ask the patient to do some stretching exercises, such as move your arms or do some squats if you can. When the person exercises what happens is that the central drive in the body will increase with increased acetylcholine release at the neuromuscular junction. So if we test the person post exercise, we will notice that the amplitude or contraction will be relatively better. It is not normal but we can notice there is a substantial increase in the amplitude of contraction.This is what is called an incremental response.
The name of the antibodies involved here is antibody P/Q antibody and this is acting voltage sensitive calcium channels which help in release of acetylcholine at the neuromuscular junction.
If this is the representation of the terminal end of any nerve, we have calcium channels which are present at the top; these are the receptors for acetylcholine. The calcium channels are the one through which quanta of acetylcholine (That is why when the calcium channels will open, then acetylcholine release will be occurring.) So these are the molecules of acetylcholine, they are lesser in patients of Lambert Eaton syndrome, and the receptors are performing fine. If we upgrade the amount of acetylcholine at the NMJ, then the performance of these patients will increase whereas in Lambert Eaton in comparison to Myasthenia gravis will have blocked receptors.
The drug of choice for this condition would be 3,4 diaminopyridine. This will increase the amount of acetylcholine at the neuromuscular junction. This drug basically acts on potassium channels. Along with this we can add pyridostigmine. The advantage of Pyridostigmine treatment will be that it will inhibit the degradation of the release acetylcholine.
The symptoms that are described by a neurasthenia patient might be the same as that of myasthenia gravis. So, it will be easy for fatigue to occur in a patient. But there is no organic cause in this case. Symptoms will be identical to Myasthenia fatigue. But there is no organic basis in this case and the testing of the patient will be normal. And the history of this patient will keep on changing like sometimes a patient will say he is weak in the morning or afternoon or evening. And we will find discrepancies every time. Like there is a plain lazy person. He or she is having symptoms that might look like Myasthenia gravis, but then there is no organic basis beyond development of the disease.
Here, there was a home delivery and the grandmother had given honey to the baby.
This would be a disaster because if the quality of the honey is bad, honey was given and the spores of botulinum toxin will germinate in the GI tract and will produce the toxin. Therefore, the patient will develop paralysis that will be a descending paralysis. Most patients of Botulism would be newborn babies who would be having bulbar palsy. The bulbar Palsy would explain the aspiration of milk, inability to feed or nasal regurgitation of fields in this child and they can also be diaphragmatic paralysis which can be life threatening. The main treatment for botulism would be to give antitoxin for this patient. This is an unfortunate complication and lots of time even without a diagnosis the child might actually die.This is also a pre junctional defect or a pre synaptic defect, so the amount of acetylcholine the toxin acts on the neuromuscular junction, and it reduces the amount of acetylcholine release at the neuromuscular junction. ;So, the common thing between Lambert Eaton syndrome or botulism is only the decrease of acetylcholine release, but the age of presentation and the Allied features are grossly different.
MG vs LEMS
|Myasthenia Gravis||Lambert Eaton Myasthenic Syndrome|
|Mainly Associated with Thymus Abnormalities||Associated with small cell lung cancer, especially with male patients|
|Acetylcholine release is completely normal. Problem is with the receptor known as Post Junctional Defect.||Acetylcholine release is less. Receptors are however normal.|
|Multiple antibodies but main are: AchR antibody Anti Musk Anti LRP4||Antibody: Anti P /Q (calcium channels)|
|Might be having Ptosis, extra ocular Muscle weakness, Diplopia, Chewing muscle weakness||Might be having Ptosis, extra ocular Muscle weakness, Diplopia, Chewing muscle weakness|
|It begins by saying a female but she will straightaway start from ptosis diplopia he will not talk about proximal muscle weakness.||Features Shoulder Girdle weakness, Proximal Muscle weakness|
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