Transcription
Okay, in our video series of Neurology lectures, in this video we are going to talk about Guillain-Barré syndrome. We are going to discuss the presentation and management of Guillain-Barré in detail.
A person got an infection—an upper respiratory infection or maybe a GI infection. Maybe the patient got diarrhea. The patient got full recovery from that infection; then the patient was totally okay, totally fine, fully recovered from the infection. But after two weeks, that patient got paralysis of the lower legs. That patient cannot feel the lower legs; the lower legs cannot move. Now the patient is paralyzed. That is a classical presentation of Guillain-Barré syndrome.
Basically, what happens is that the patient gets an infection, and antibodies are formed against the virus, the bacteria, and those antibodies kill the virus, kill the infection, and the patient gets full recovery. But those antibodies now damage the neurons of the body. Those antibodies injure the myelin sheath; they damage the myelin sheaths that are present over the neurons, therefore resulting in neuronal injury. The neuronal injury results in motor weakness, sensory disturbance, resulting in paralysis. That is called as Guillain-Barré syndrome. There is polyneuropathy—nerve damage. It is symmetric; it is present on both sides. It's not like Parkinson's or any other disease in which there is asymmetric presentation. In Guillain-Barré syndrome, there is symmetric loss of function, and it is usually in the ascending manner. It first involves the feet. If there is loss of ankle reflexes, there is weakness in the leg, and it starts ascending upward. It can involve the limbs, and at the end, the most dreadful complication of Guillain-Barré syndrome is the paralysis of the diaphragm, resulting in respiratory arrest, that results in death of these patients. There is flaccid paralysis due to damage of the motor neurons, and it results because there are cross-reactive antibodies. The antibodies that are formed against the infection are now damaging the own neurons. That is the syndrome.
The pathogens that are considered to be associated with Guillain-Barré syndrome: the most important one is Campylobacter. In exams, most commonly you will be asked about Campylobacter. For academic purposes, remember Campylobacter causes diarrhea; it causes bloody diarrhea. There will be a scenario that a patient, a young patient, got an episode of diarrhea, and after two weeks, after three weeks, that patient got paralysis of the lower legs—loss of motor function of the lower legs. That is the syndrome. The most common viral cause: Cytomegalovirus, and these days Coronavirus cases have been associated with Guillain-Barré syndrome. For real life, any type of infection can result in Guillain-Barré syndrome.
This is a picture showing a neuron. These are the dendrites; this is the cell body; this is the axon, and that axon is myelinated with myelin sheath. It is covered by myelin sheath, and myelin sheath increases the conduction of nerve impulses. The target of these antibodies is the myelin sheath. The antibody-mediated destruction, demyelination of axon takes place. That myelin sheath is damaged by these antibodies, and when the myelin sheath is absent, the conduction is slowed down; the conduction is absent; therefore, there is loss of motor function, and there is also sensory symptoms associated with Guillain-Barré syndrome. And remember one important point: that there is segmental demyelination of neurons. Segmental demyelination means that a certain segment of the spinal cord gets damaged. It can be either cervical; it can be lumbar; it can be sacral; it can be any segment of neurons. It is important to remember the segmental demyelination because when we will discuss the atypical subtypes of Guillain-Barré, in those subtypes certain segments of the spinal cord will be damaged, and those certain segments will produce certain specific symptoms. So, segmental demyelination takes place.
Now coming to the presentation of Guillain-Barré syndrome: the classical presentation would be that the patient got an infection two weeks, three weeks back—maybe an upper respiratory infection, maybe a GI infection—and now, uh, slowly and gradually patients start to feel weakness in the lower legs. The patient starts to feel paresthesia—abnormal sensations in the leg—and slowly and gradually there was weakness, and one day he woke up in the morning and he could not move his legs. Symptoms start as paresthesia, affecting the distal extremities, back and limb pain—the lower limb pain. It is an ascending paralysis; it's a flaccid paralysis, and there is stocking-glove distribution—symmetric distribution. Now, in atypical types, maybe you might not find this type of ascending paralysis in which there will be a different type, but we will come to that later. For now, just remember that there is the classical presentation that it would have an ascending paralysis—Landry paralysis. Respiratory failure. Landry was the person who described the phenomena of Guillain-Barré syndrome. The most dreadful and the most important complication that a doctor has to consider is the respiratory failure. These patients are at high risk of developing respiratory or diaphragmatic paralysis, resulting in respiratory failure and death of the patient. Therefore, you would see that these Guillain-Barré syndrome patients are mostly present in ICUs because these patients need ventilatory support. Ultimately, these patients develop respiratory failure if they are not managed properly. So, respiratory failure is the most dreadful complication. Reflexes—the reflexes are reduced or absent, and it starts from the legs—from the ankle, then knee reflexes, and then it progresses to the upper limbs. Autonomic dysfunction is a very important part of Guillain-Barré syndrome. What you would see is that the autonomic nervous system would be damaged by these antibodies, and it would present as that sometimes the patient's blood pressure will be shooting upwards, and sometimes you would see that the patient is getting hypotensive; gradually he's getting, he's losing blood pressure; the blood pressure is going down; the patient is showing arrhythmias on ECG. This is because that the patient's autonomic nervous system is disturbed; it's confused, and sometimes it is hypotensive; the patient is hypotensive; sometimes it's hypertensive. Basically, what happens is that initially patients get neurogenic shutdown—neurogenic failure. The neurogenic failure results in hypotension, loss of heart rate—bradycardia, hypotension—and then the body realizes that the body is losing blood pressure, losing heart rate, and it activates the reflex mechanisms. Those reflex mechanisms increase the blood pressure and increase the heart rate, and they now overshoot and they also result in arrhythmias. So what you would see is that you would see arrhythmias, blood pressure dysregulation—sometime hypertensive, sometimes hypotensive. Voiding dysfunction. Cranial nerve involvement is seen as soon as the paralysis moves upward. Bilateral facial palsy is seen in Guillain-Barré syndrome in the progressive cases, and there are atypical Guillain-Barrés as well. In atypical Guillain-Barré syndrome, there are different syndromes in which only these cranial nerves are involved. We'll discuss them later. Glossopharyngeal nerve—abnormal gag reflexes. Patients won't be able to speak; these patients won't be able to talk; they won't be able to swallow food. So, vagus nerve damage can also be seen.
Now coming to the subtypes: this ascending paralysis—not all patients of Guillain-Barré syndrome always have this ascending paralysis and the classical presentation. For exams, it's good to remember the classical ascending paralysis, but in real life there will be many patients who will be labeled as Guillain-Barré syndrome, but they will not be having this classical ascending paralysis presentation. In the subtypes are the variants. The Miller Fisher syndrome is an important one to remember. In Miller Fisher syndrome, there will be cranial nerve involvement. It is a rare form, but you should remember that there is not an ascending paralysis; it is not present in this type of condition. In this type, what you would see is that you would see cranial nerve involvement. In cranial nerves, there will be ophthalmoplegia; the cranial nerve three, cranial nerve four—these nerves will be damaged. There will be ataxia; there will be areflexia. So this is a classical triad of Miller Fisher syndrome, and you won't be able to see this classical presentation of ascending paralysis in these patients. Another subtype or variant to remember is multifocal motor neuropathy. Multifocal motor neuropathy—it basically affects the motor neurons, and it spares the sensory ones. The sensory ones are spared, and it has asymmetric paralysis. It means that one side of the body will be affected; the other side won't be affected. As we said in Guillain-Barré, there is usually in the classical Guillain-Barré, there is symmetric involvement—symmetric ascending involvement. In multifocal motor neuropathy, maybe the one side is affected—one hand is affected—and the motor—there is motor loss; there is no sensory loss. In the classical Guillain-Barré, we said there will be also sensory damage to the patient, but in multifocal motor neuropathy only motor damage is there, and it is asymmetric, and it usually starts from the upper distal limb. So that is multifocal motor neuropathy. Another subtype or variant is acute motor axonal neuropathy. It affects the motor neurons, and it spares the sensory fibers, just like the previous one. It has areflexia without sensory loss.
Now coming to the diagnosis: in the diagnosis, the best initial test, the first test that you need to do is take the CSF and examine it. What you would see in CSF is that in CSF there will be normal cell count; there will be normal glucose levels; there will be normal color; everything will be normal. The single thing that will be elevated will be the proteins. The only finding would be elevated proteins. That is called as albuminocytologic dissociation. The albumin, the protein is high, but cytology—the cells—they are normal. Normally, what you would see is in infections: in infections, what happens is that the cells go up; the proteins also go up. But since it is an autoimmune disease, there are antibodies present in the CSF. It's not an infection; it's basically the antibodies that have entered the CSF, and antibodies are proteins, so the antibodies are there in the CSF; therefore, proteins are high, and the cells are normal. That is called as albuminocytologic dissociation—increased protein levels in CSF, normal WBC count. High CSF cell counts indicate GBS is unlikely. If the proteins are high and cells are high, it means that it's most likely an infection that is causing it because cells are high; the WBCs are really high if there is infection. But since in there is no infection, it is just the autoimmune antibodies that are damaging the neurons. So if the CSF contains cells, it points away from Guillain-Barré; it's most likely infection. Because in Guillain-Barré the proteins will be high; the antibodies will be present, but the cells will be normal. After you have done CSF levels and you have found that there are elevated proteins with normal cell count, the next thing that you would do to confirm the diagnosis would be nerve conduction studies. In nerve conduction studies, you give certain electric signals, and you see the conduction through the nerves. Since these patients are having damage to the myelin sheath, the conduction will be abnormal; the conduction will be absent; there will be decreased conduction due to demyelination. That will confirm the diagnosis of Guillain-Barré syndrome. Another test that you can perform is electromyography. In electromyography, what you do is that you basically give signals to the muscles. The neurons give signals to the muscle; you give signals to the neuron, and you see whether those neurons are conducting the signals to the muscles. When the neuron gets, gives signal to the muscle, muscle contracts. So you give the signal to the neuron, and you see whether that signal is transferred from neuron to the muscle, and when there is demyelination, there will be reduction in the transmission or absent transmission. Electromyography. An important test that you can do is ECG. In ECG, as I said, there is a high risk that these patients can develop arrhythmias. These patients are sometimes tachycardic, sometime bradycardic. And another thing, as I said, that there is autonomic dysfunction in these patients. Normally, when we breathe, is that you can feel that whenever you inspire, during inspiration there is increase in the heart rate; it's normal physiologic phenomena. And when you expire, there is decrease in the heart rate; it's normal; it's physiologic. But since, and it is controlled by autonomic nervous system, but since autonomic nervous system is damaged in these patients, in these Guillain-Barré patients, when these patients will breathe, inspire, the heart rate would not increase. That is called as impaired heart frequency variation during breathing.
Now coming to the treatment of Guillain-Barré syndrome: when you understand the pathology, the treatment gets so easier. The most important thing, as I said, is respiratory failure. Now we have to handle the respiratory failure; we have to again and again examine the patient; we have to keep an eye on the respiratory status of that patient—that that patient does not develop any respiratory failure. Impending respiratory failure is an indication that that patient needs an ICU care. Now, as I said that mostly these Guillain-Barré patients are present in ICU; these patients need ICU care. Now, what are the indications? What are the points when you need to send the patient to ICU? If there is impending respiratory failure; if the patient gets short of breath while speaking; if there is use of accessory muscles; if you ask the patient to count up to 50 and that patient can hardly count up till 15; that patient can count less than 15 in a single breath—like this: one, two, three, four, five, six, seven, eight, nine, ten, eleven. Now this patient cannot even count up till fifteen. A normal person can count up to 40-50 in a single breath, but these Guillain-Barré patients will be having respiratory failure, and they will, they won't be able to count up to 15. This is an indication that a patient needs an ICU care. Increase respiratory rate with the tachycardia; abnormal ABGs showing respiratory acidosis with hypercapnia—increase CO2 retention; severe weakness; autonomic instability—sometimes the blood pressure is overshooting; sometimes it's very low; cardiac arrhythmias. These are the indications that that patient should be in ICU. What are the indications of intubation? There are points when they're the respiratory failure is taking over, and you need to give or you need to intubate—the automation; you need to pass the tube and ventilate that patient. If you want to understand ventilator, I have talked about it in detail in my video on ventilator mechanics—the very basics of ventilator mechanics. You can check out the link in the description below. The indications of intubation include: if the respiratory rate is greater than 30—normal respiratory rate is between 15 to 16. If the patient is dropping oxygen saturation—that patient is not maintaining oxygen despite giving oxygen through oxygen mask; if the patient is having acute hypercapnia—CO2 retention; bulbar dysfunction with swallowing impairment—as I said that these patients can develop cranial nerve involvement, and these patients will be unable to swallow. In some cases where there is cranial nerve involvement, now this this patient can't talk; this patient can't swallow; this patient needs incubation because this patient can't protect their airway because the important point is that if the patient has bulbar dysfunction, that patient has absent gag reflex; this patient cannot protect the airway; that patient will have a weak cough reflex; there will be secretion accumulating in the airway, and thereafter some time that patient will develop severe respiratory distress. Inability to clear the secretions—we cough reflex, we gag reflex. Now, since the patient is paralyzed, this patient will be having stasis of blood, and whenever there is stasis of blood in the legs, there is increased chances of DVT. You know, normally when we sleep, we always keep moving our legs; after sometimes you always feel the need to change the posture. It's a natural mechanism; it's a natural mechanism to prevent deep vein thrombosis. You keep changing your position; you keep moving just to make sure that there is no stasis because whenever there is stasis, when some when when the person stays in the same position for a long time, there is increased chances of hypercoagulability—stasis of blood resulting in hypercoagulability and clot formation, and that results in the formation of DVT. You use low molecular weight heparin—prophylactic doses; intermittent pneumatic compressions that cause compression of the legs and keep compressing the legs so that the blood keeps flowing and there is no stasis. Compressive stockings so that there is no edema due to stasis. Pain control—usually these patients also have injury to the sensory nerves, and those sensory nerve damage causes abnormal sensations—paresthesias, pain. If the pain is neuropathic, use gabapentin; carbamazepine; simple analgesics and NSAIDs can be used for pain; opiates can also be used if the pain is severe.
Now coming to the main therapy—the main treatment of Guillain-Barré syndrome—that is the immunomodulatory therapy. Immunomodulatory—you modulate the immune system; you manipulate the immune system. Basically, it's an autoimmune condition; the immune system is damaging the body. What you do is that you control the immune system; you control the immune system and slow down the disease progression. So it's important that you give this treatment earlier, as soon as possible, because if the immune system is already damaged the neurons, you cannot reverse the damage. What you can do is that you can slow down the process; you can control the process by controlling the immune system. So IVIG—IV immunoglobulins. IV immunoglobulins are basically immunoglobulins—antibodies that bind these antibodies and clear them away from the blood. So we are, there is antibody that is damaging the neurons; we are giving antibodies—IV immunoglobulin from outside—and those IV immunoglobulins bind these and neutralize these antibodies and clear away these antibodies. So IV immunoglobulin works in such a way. Another thing is plasma exchange. In plasma exchange, what you do is that you take plasma out from a person, and you filter the antibodies out, and then you give the plasma back to the patient. That is called as plasma exchange. Plasma exchange needs a bigger setup, and it is associated with more complications. So most commonly IVIG is more easier, although it's costly, but it is more easier to give, and it is preferred over plasma exchange. But remember, remember if someone asks you which one is more effective, remember both of them are equally effective; both of them have equal efficacy. You have to give it within four weeks of onset of symptoms. If the patient is having severe symptoms, then immunomodulatory therapy is given. Remember, not every patient is eligible for immunomodulatory therapy. If the patient has a very mild case of Guillain-Barré and that patient is already recovering from it, so that patient might not benefit from immunomodulatory therapy. But in a patient that is getting worse, you need to give immunomodulatory therapy as soon as possible. If the patient is unable to walk 10 meters independently, or if the patient is having rapid deterioration—in the morning the patient was fine, but now the patient has loss of grip; that patient cannot even grip; you give the patient a paper, and that patient cannot hold that paper; now anti-gravity strength—that patient cannot lift the arm; now that patient cannot even walk up till 10 steps; now so that patient will need immunomodulatory therapy. Stable patients with isolated ophthalmoplegia, areflexia, ataxia of Miller Fisher syndrome—remember if the patient is having Miller Fisher syndrome and that patient is not having any other deficit like respiratory failure or any other limb weakness; it's just these cranial nerve involvement, ataxia, areflexia, and ophthalmoplegia—that patient also does not need immunotherapy. Immunotherapy in such cases is given if there is involvement of respiratory system or if there is involvement of limbs with severe weakness.
Now how do you give IV immunoglobulin? IV immunoglobulin is basically given IV—IV infusion. But before giving this, what you do is that you give 500 mL of normal saline because they can, these IV immunoglobulins can cause acute kidney injury and hypotension. So we prophylactically give 500 mL of normal saline. We give acetaminophen because they cause pain and fever, and they can sometimes cause an allergic reaction. So we prophylactically give diphenhydramine—25 mg 30 minutes before the infusion. IVIG is given at the rate of 0.4 gram per kg per day for 5 days. Infusion is started at 0.3 to 0.5 ml per kg per hour and as slowly and gradually increase the speed up to 6 to 8 ml per kg per hour, as if the patient is having no reaction, no problem, no adverse effects, so you can increase the rate. Adverse effects include hypotension, nausea, headache, acute kidney injury, transfusion reactions. So for that purposes we have already given prophylactic medication. Plasma exchange—plasma exchange needs a bigger setup in which you take the plasma out, you filter that antibodies, and you give it back to the patient. Four to six treatment sessions are done over eight to ten days, and they are given within the four weeks. Within four weeks is important. Adverse effects include hypotension, sepsis, transfusion reactions. An important thing to remember is in many autoimmune diseases what we do is that we give steroids to the patient; those steroids suppress the immune system. But remember, in Guillain-Barré syndrome steroids are useless; steroids are useless. You do not give steroids in Guillain-Barré syndrome.
Now coming to the prognosis of Guillain-Barré syndrome: remember, Guillain-Barré is a dreadful condition; it scares the hell out of the patient and the attendant. Just imagine that you are lying in the bed, and tomorrow morning you wake up and you are paralyzed. It's a very dreadful condition. Many of such conditions that take you till—is you. And then the good thing about these conditions like tetanus, Guillain-Barré syndrome, that there is a good recovery in this patient. The prognosis is good. Neuroleptic malignant syndrome—these are the conditions that that scare the hell out of the patient; this they are very painful for the attendants as well. But the good thing about Guillain-Barré syndrome is that it has a good problem. So 70 percent of the patients have good prognosis. The disease progression peaks in two to four weeks, but after that there is a good recovery in Guillain-Barré. Symptoms recede in the reverse manner. Now the last thing to occur will go away first. Now if the patient had cranial nerve involvement and absent gag reflex, now in recovery phase the gag reflex will recover first, and the limbs will recover the last. So recovery is in the reverse manner. Three to seven percent of the patient die due to respiratory failure.
Now another important point that I want to mention here is another condition called as transverse myelitis. I'll make a separate video of transverse myelitis as well. In transverse myelitis, basically the patient gets a respiratory infection, and after that respiratory infection the patient has paralysis. In transverse myelitis, bowel and bladder incontinence is almost always there. Syndrome—bowel and bladder may be involved, but it is not always involved. In transverse myelitis, there is a sensory level—a sensory level. The patient can point out to him to you that, "Doctor, below this I cannot move my body; below this point I have severe pain in my body." In transverse myelitis there is severe pain in these patients—stabbing pain, as someone has taken blades and they are cutting their skin. So if we are burning pain, and they would tell you that below this point there is a sensory level; below this point I have this problem. In Guillain-Barré syndrome, there is no prominent sensory level below which the problem is going in the, there is a progressive loss of function. So there is a difference between transverse myelitis and Guillain-Barré syndrome.
Before going into summary, if you liked my video, please click on the Subscribe button. After an, after an infection, patients gets nerve damage. Pathogens involved; damage the symptoms—ascending paralysis; the reflexes are lost; autonomic dysfunction; cranial nerve involvement; the subtypes; the diagnosis with CSF as initial test; nerve conduction study; electromyography—an important test to confirm the diagnosis; indications of ICU; indications of intubation; DVT prophylaxis; axis and pain control; immunomodulatory therapy—IVIG is more commonly used; plasma exchange needs a bigger setup; more side effects, but they have equal efficacy—both IVIG and plasma exchange; steroids are not used; it has a good prognosis. If you liked my video, please click on the Subscribe button and check out my other videos on neurology lectures. The link of those videos is given in the description below. Thank you very much.