Parkinson's Disease : Pathophysiology, Diagnosis and Mx

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Parkinson's Disease : Pathophysiology, Diagnosis and Mx

2 Aug, 2 PM

[Music] to everyone uh welcome you and we have dr vinit vanga with us he will be talking about parkinson's disease uh we discussed part one a few days back you can go and catch up on that uh in the replay section and today we will be discussing part two welcomes and thanks a lot for your time over to you thank you thanks first of all i like you i like to thank uh the netflix for having me on this academic discussion and without any delay we'll uh right away begin with our session for today which is parkinson's disease part two so we discussed about parkinson's disease pathophysiology diagnosis and a bit of management what we are going to discuss is discuss about the parkinson's disease management in details so we know the natural history of parkinson's disease is that initially the patient responds very well to treatment which we call it as a honeymoon period subsequently patient starts having motor complications then subsequently there are certain symptoms which are resistance to levodopa uh and other medicines which is a resistance symptom period and subsequently the patients start having cognitive decline what is the therapeutic principle there are therapeutic principle is two priority is to use drugs which have established protective uh mechanism and neuroprotection encourage patients to remain active and mobile also preserve uh independence of mobility and individualization of therapy so you take principles that guide the treatment however to stages of parkinson's disease so uh there are mainly early at moderate and advanced stage or end stage so early disease in which there are very mild symptoms and there are no limitations to activities if it starts remaining activities it further progresses in moderate disease uh the response to uh the dopaminergic therapy actually start to going down but there are no motor complications and disease or advanced uh complications so if you uh discuss uh if you see uh the dopamine precursor levodopa is the main stay of treatment but we can also use uh dopamine inhibitors along with it to reduce its metabolism we can use dopamine agonist we can use catechol or methyltransmits inhibitor which also blocks the heart half-life of levodopa the dopamine we can also use certain drugs which can help in dopamine release such as amentidine and then there are mao inhibitors a and b as well as dopamine synthesis so we have dopaminergic drugs which are two types either levodopa which is a precursor of uh syndopa synthesis and the second is uh dopamine agonist which act on receptor directly then maopi inhibitor and cmt animators both act in a way to increase dopamine availability and amentidine obviously is as this dopamine secretion so this chart actually will tell you in brief uh if you want to like just go through one slide telling you everything this can tell you about the initial doses how to begin it up how to ramp it up and what are the main side effects we'll discuss these ones uh one by one so dopamine precursor levodopa is usually combined with carbo dopa to decrease its metabolism and increase its level uh dopamine about a four full reduction of dopamine doses can be uh achieved if you combine carbidopa which is a decarboxylase inhibitor so this is how it works comt in emitter and [Music] and this can be divided into either relative aggregate derivatives or non-angular derivatives previously the aggregate derivatives were most commonly used like bromocriptin carboxyline but they have a lot of side effects non-aggregate derivatives primipegs or droprinine or epomorphine hypomorphine in fact is the new sensation in parkinson's disease because of a misguiding video by one of the prominent hospitals in india but uh non-aggregate derivatives are premi pixel drop renin or lepromorphine uh the adverse effect of these are drowsiness leap attacks orthostatic hypotension uh confusion is one of the major problems with these along with sedation apomorphine uh has an emesis producing propensity this the patient should be treated with anti-nauseating medicines such as doom peridone or methyl benzomide uh so agar derivatives are very prone to cause red inflamed skin and pergolite and these are causing problems so what is the uh what is the treatment dogma is to start with a very very low force and then gradually wrap it up don't start with the high to those so the patient has a high side effects grammy paxol is to be started at 0.125 milligram at bedtime for first three days and then uh subsequently you can increase 0.125 milligram per day weekly the maximum dose is around 40 milligram draining can also be started at 0.25 milligram three times daily so these are the receptors on which these act so we have to start with a very low nose and use the lowest side effects the patients can be switched to one drug to another based on their equivalent doses such as premi pixel can be switched to raw cranial or others and that the the doses in which it should be started the maintenance stores and the maximum dose is very clearly written in this slide so i have i have particularly used these slides for uh students and whosoever are attending so that they need there are certain slides they can just use for a ready referral system so what is the lowest possible dose when to start so equivalent doses how do we divide so premier pixel one is to five is premier pixel versus propane load so mainly these two will be used so aventadine now coming on to amended in how does it acts it's blocks the glutamate receptors it has anti-musculin effects and it blocks the dopamine reuptake so increases the dopamine availability to the brain so uh it's a very quick concept of actions one of the most important drugs to treat dyskinesia especially if it is this correct dyskinesias the side effects are limited reticularis encode edema hallucinations confusion so all of these are there and on also anti-musculinic side effects so you should be very are these uh [Music] side effects if you are giving patient uh it can be given a very early as in monotherapy but usually uh right now nowadays the top is to use a dopamine agonist especially if it is early onset parkinson's and those patients who have parkinson's below 60 below 50 and then gradually added up so amended in usually most of the neurologists use it as a reserve truck for a later stage of parkinson's and advanced perkins especially to treat dyskinesias and off period comt inhibitors there are two types enter upon toll coupon they are not to be used as monotherapy and used to be to be used only with levodopa because they increase the levodopa availability they've been found to increase the on time by one hour and they have the side effect profile in the form of better toxicity and diarrhea especially with the tall capone it also reduces enter common produces yellow discoloration of urine so what has to be done is uh and take up one has a relatively shorter duration of action and its 200 milligram tablets need to be given simultaneously with carbidopa levodopa so this will increase the overall dopamine availability if you give it because it will prevent the metabolism coming on to mao inhibitors there are two more b and a and b both so b are the most commonly used celery gelatine glazing and saphenomide sophenamide is one of the most important molecules being used nowadays previously resilient and saline they also have been found to have neuroprotective mechanism these can be used very early in the treatment course this is very important as to be noticed that the these can be used as an monotherapy especially in early parkinson's disease patients and suffena white can be used in an add-on to increase the on-time effects and they can not be taken with levodopa so that's something that is to be taken into consideration because they can cause cheese reaction so a tall cup on enter coupon has to be taken with levodopa while among animators are not to be taken with levodopa's [Music] now how to approach the dopaminergic side effects of these medicines so if your patient has nausea additional carbidopa may be addicted to relieve nausea orthostasis this can develop later in the course of disease the patient can have confusion and hallucinations they usually develop later so you have to see uh the disc how to how do you withdraw the drugs for example a patient presents to you with the confusion and hallucinations and he is already on treatment for parkinson's disease so how would you go about so first drug to be stopped is anticholinergic subsequently stopped amentidine then mao inhibitors then dopamine agonist then comp inhibitors and finally levodopa it's very important to go this way only the patient on uh especially on dopamine agonists can heavily impulse control disorders so they can be uh the impulse control disorders can be found in patients on lego dopa as well but the most common with dopamine agonists so you have to be cautious with the the treatment now dopamine risk regulation syndrome is the compulsive so patient may come to you in the operating system the patient is keep on taking syndopa continuously without uh without stopping it so this is a problem the patient's relative will come to you because the patient wants to be on certain dopamine dysregulation syndrome and patient has been compulsively impulsively taking dopamine so it basically involves mainly the male patients especially those with early onset parkinson's disease and uh despite increasingly severe drug related dyskinesia it's in cyclical mood disorder so uh it's very important that you have to diagnose this dopamine dysregulation syndrome impulse control disorders they have to be first diagnosed and then treat it and they are not only related to syndopa side effects they can be part of the disease process because as a dopa has a mood elevating property so it's in cyclical mood disorder funding gambling uh collection of things and those things can be very well found in these patients so dds is not very well studied with regards to management but what you do is limit the dopaminergic dose especially dopamine agonist and gives apomorphine which is a very good drug in these patients so what what usually happens is 75 percent patients usually start having complications of five five years of liver dopa therapy younger patients are more predisposed to have this side effect where the older patients are less controlled but you see 25 patients have good response 43 percent have trouble some fluctuations 20 percent has doubled some dyskinesia 8 have loss of efficacy so how do you go about it so early stay if the patients are mild symptoms and there are no threat to patient activities start with dopamine again especially if the patient has presented to you very early if the patient is more than 65 70 then it's always also good to start with lego dopa very low dose and then also at neuro protective engineering such as celadely resilience afenamide they are mao inhibitors so data top study was one which uh had an uh celebilline used uh which reduced the updrs worsening as well as prolonged symptomatic effect so there have been many studies and i'm not going to go into detail of these because they are not they're not of too much of use clinically so if the patient presents with the mild disease early use dopamine agonist mao inhibitor and if the if the patient is quite old like 70 is type then you can use levodopa treatment of mild disease then when the signs and symptoms start to become interfere with your quality of life then uh you should start using either lego dopa or you should use levodopa sparing indians liverpool's pairing is dopamine agonist or mao inhibitors so uh as such uh there are two school of thoughts one school of thought says that we should preserve liver dopa for a later dose because liver dopa can cause dyskinesia especially after some use of action but it has been another school of thought is that especially if you you're if you don't use levodopa very early even if you use late levodopa tends to have less effect and the dyskinesias come even earlier so and it is also proven that levodopa is the most epic asia stuck so there's no point so the another school of thoughts is that there's no point preserving the levodopa for a lot of dose because the patient cannot enjoy his life and it leads to poor quality of life dopamine agonists are the second most powerful and less likely to induce dyskinesias but there are no evidence of neuroprotection monotherapy is effective only in 30 percent of patients and delayed onset of motor complications by delaying levodopa introduction but they have a limitation in the form of side effects such as hallucinations and sedation hemantidine is one of the the other derivatives are bromocriptine carbohydrate so they have certain side effects but non-arabics are good uh amentadine has indirect dopaminergic action as it as i told you it uh increases the dopamine release from storage side and some anticoal energy property uh delayed onset of benefit and short lift benefit is uh the thing and at the adverse effects we have already discussed the usual dose is 100 milligram pid to qid levodopa is the most effective uh drug till date uh and it has been associated with improved quality of life and the patients tend to do much good but the problem is dyskinesias the current approach or that this approach differs with the neurologist and amongst physicians so in general how do i practice is the patient is uh less than 60 i start with dopamine again take it to a dose the maximum tolerated dose where the patient doesn't have symptom try to make uh do make it the only therapy like on the single drug for at least till the time the patient tolerates it usually around one to two years the patients stop having a patient starts having problems with dopamine agonists they don't do well and start having symptoms so we begin with levodopa laters those patients who present with to me later for example 65 70s then uh i usually start with levodopa and then case of dyskinesis fluctuations change the dose of levodopa carbidopa combination and then add these medicines so the moderate disease obviously you need liver dopa start with lowest possible dose so those fluctuations can be there only two thirds of plain liver dopa dose is absorbed that's very important we can use enter coupon to work upon to uh treat these complications such as wearing off effects and all these so when do we start levodopa carburetor process they are under available in 100 125 and 250 25 this is liver dopa carbidopa combination so either cinder populars or like thai domain or there are many other brands which come so hundred hundred twenty hundred ten hundred twenty five and then two hundred fifty so uh seventy five milligram per day of carbidopa should be given to these patients so that increases the levodopa availability so it's always better uh one should start with at least 125 milligram when the drug is introduced and increase 125 milligram per day per week until three times daily dosing achieved in ophthalmic so not every symptom of parkinson's disease but what are the more troublesome symptoms are motor symptoms motor symptoms respond to liver dopa amazingly then tremors can be a bit more resistant you can use anti-cholinergics but they have had their own side effects and anti-core energy can lead to dementia in these patients so that's a problem but it's important that you start levodopa at a good dose before saying that the patient is not responding take it to the highest possible dose we can we usually take the patient to eight hundred two thousand milligram of levodopa before saying that it is not effective but it can be taken up to two thousand milligram usually indian patients don't tolerate this much of lego dopa only around thousand milligrams of liver dopa the patient starts showing side effects so there is they are also available in sustained release formulation and sustainability formation tend to have a more consistent drug availability but at the same point of time they have certain side effects now coming to advanced pork instances so there are certain uh symptoms of parkinson's disease such as falls postural instability freezing uh all these start happening and then they're certain of some of these are because of syndopa resistance and some of these are because of uh other things other than sindhupa so uh they are not responsive to levodopa fluctuations can be wearing off when the the divo dopa gradually when and then starts going down very fast before you start taking the next row so it's like a peak in transit like this so if you want to stop this from going down you give lever doppler here so what you need to do is increase the frequency of levodopa then there is your showing suddenly the patient has effect suddenly the patient goes down there can be dyskinesias which can be peaked dyskinesia diphasic or on and sensory behavior autonomic symptoms so what is the pathogenesis of fluctuations that they are altered dopaminergic mechanisms uh post synaptic level their bearing of initially reflex depleting dopaminergic storage and results in downstream deceptive dysregulation so how do we treat it uh the wearing off is treated by a small because of the small dopamine storage capacity so what we do is if there is mild bearing of we add mao inhibitor and and then bridgely increase it we also can use a sustained release formulation we can as cmt and limit as amended in and increase the dose or decrease the interval and also can use liquid formulation often on phenomena if the patient has sudden of the best duct to be used is hypomorphine uh and the random offs are less prediction and usually the patients have a predicted organelle for example the patient will tell you that he takes the syndrome at 7am he is he feels better by 7 30 and by 9 or 10 he starts the effect going down so these are predictable then there are certain uh offs which are not predictable the patient suddenly has effect and suddenly is go down and then suddenly he becomes again normal which is a problem so ah subcutaneous hypomorphine a new dose of liver dopa increasing frequency decreasing the dose all of these can be then you can look for you should look for the drugs which are and which are acting against levodopa uh so delayed on can be there especially the effect after 30 minutes mechanism is inadequate peak plasma level they can be super off in which the desensitization of receptor takes place the you have to give syndropa uh within our gap with meals so don't never give it so if the patient is taking with means the patient can have delayed gastric emptying and delayed response and high protein meals tend to compete with the levodopa uh so it is to be avoided so high protein diet is to be avoided in these patients uh freezing can be on freezing can be of freezing uh hypomorphine and amentadine are one of the most commonly used drugs for freezing uh the known major risk factors for peak dose dyskinesias are the more the severe the disease the more the duration of the disease the more other response of petros dyskinesia such as the levodopa dose is increasing of the patient and duration of levodopa therapy so how do we treat it reducing a liver dopa a low dose result in dyskinesias amentidine can be used but usually uh the high dose of levodopa results in dyskinesia so you have to reduce the dose increase the frequency overall maintenance therapeutic level dextromethorpene close up can also be used for treating dyskinesis dyskinesias are of two type deficiency weakness you increase the lows and the maximum dose the patient starts having disclaimers down is obvious when the patient becomes suddenly off when the logo doper goes down and bike is he has side effects in both the levels so we have to use how do we treat it uh it can be due to differential sensitivity of type 2 dopamine receptors and one of the most important thing is to use dopamine agonist yoyoing is the patient fluctuates they have been unpredictable of so once and the patient starts having this so what you do is you have to give very small dose with increased frequency in a dissolve so dissolve the liquid open lemon water and give it their lego dopa pumps as well uh finally if these patients don't respond to anything deep brain stimulation is one of the most effective method in these patients but there are certain contraindications such as behavioral symptoms dementia patients not responding to syndrome actually are not the candidates for deep brain stimulation but those patients who respond well to syndrome don't have uh dementia or behavioral symptoms and less of non-levodopa non-motor symptoms these patients are best candidates for deep brain stimulation and these these kinesias off and on can all be treated with deep brain stimulation there are many sites i'm not going to go into detail of it uh then there are non-dopamine energy occasions for motor symptoms such as anticholinergics anti-histaminics muscle relaxants antioxidants mitochondrial enhancers neurotropins so all of these can be used and i'll i'll finish my presentation here and if there are any questions i am here to answer thank you thank you sir thank you so much for the session and we'll quickly move on to the questions so the first question is uh i think it's a question more related to part one uh dr uday kulkarni wanted to ask what are the earliest clinical signs of parkinson's disease so earlier clinical science as i said uh bradykinesia slowness in general and trendlessness especially at rest which is a coarse tremor low frequency tremor at rest stiffness slowness so these are the most common and earliest symptoms so the patient will tell you about uh that he has not been he is not as fast as he used to his hands have started trembling sometimes the patient comes with shoulder stiffness stiffness of one side of the body will say like my shoulder is becoming stiff i am having constipation so early uh pre-motor symptoms of parkinson's has to be looked so these are shoulder stiffness constipation depression anastnia so these are pre-motor symptoms so even before the motor symptoms start growing these are the pre-motor symptoms so you have to be cautious about elderly patients coming to you with these components we very early very easily label these patients to have depression or some other thing before we label them to have depression you should also consider whether an evidence of parkinson's associated or not okay thank you next question by dr ambaram is tremors in one or two fingers in only one hand uh so that is the only complaint which drop to start yes so which drug would you advise for that so if the patient has only tremors the first thing that you need to ask the patient is whether these tremors are troublesome or not if the patient doesn't have any problem with tumors don't treat it if the patient has trouble the first thing that the things that you can use is you can use sindopa lodos you can also use a dry hex infinitive anticholinergic you can use chronic form you can use propranolol so these four drugs can be used okay great dr gotami has a question if you could highlight some effective non-formal pharmacologic ways to manage pv and when would pharmacologic therapy be ideally recommended to be initiated so the ideal so the patient actually asks answers this question for you you ask the patient you look at the patient whether he is dependent for activities of daily living or not how troublesome are the symptoms if the symptoms are troublesome and it is leading to problems with daily life of the patient then you should go ahead and start the therapy if the patients doesn't have symptoms that much symptoms which are troublesome are causing problems with activity [Music] then you can so it has to be discussion with the patient when the first time question comes to you tell about this this is how i'm gonna treat it you are at present if you don't have any troublesome symptoms we can wait for a while and then subsequently start so now coming on to non-pharmacological uh gait training exercises uh being active and agile using a lot of head and back is very important in parkinson's disease so all of these are non-pharmacological uh ways of treating okay uday when do you advise gastrostomy gastrostomy is reserved for patients of very very advanced parkinson's disease those who are not able to don't have to reflect them like uh cutting out choking regurgitation so these patients some very advanced stage need [Music] otherwise next question is by dr prajwal bhansal do the parkinson's medicine remain for whole life or is there any cure that after this you won't have to take the medicines so with time it's gonna go down this has to go down because it's a degenerative disorder it is related so uh if you start if so the question is very simple if the dopamine levels in the brain and the body are going to go down the medicines have to be there in fact the dose has to be increased with time you cannot stop right okay next question we have two doctors asking the same question are there any laboratory investigations or tests to diagnose parkinson so there are certain tests for example fluorodopa products can can be done product pet ct can be done to see a dopamine uptake in the brain and whether it's asymmetrical uptake those were the questions for today so i would like to thank you on behalf of netflix thank you so much thank you for joining us and thank you to our audience as well there's one more question yes if a younger person is present so yeah so the younger patients you have to be a bit more careful before labeling it to be idiopathic parkinson you should look about genetic parkinson's other treatable form of parkinson's such as wilson's disease genetic parkinson's so all of these have to be considered before labeling it to be idiopathic parkinson's so yes you should focus on differential diagnosis but eventually you have like differential diagnosis can last for a day for a week eventually you have to reach a provisional and a definite diagnosis so once you diagnose that this is the cause of this tremor so this parkinsonian symptoms in these patients you have to treat that for example if it is wilson's you treat persons if it is genetic parkinson's obviously you treat it so depending upon what is the pause you treated right oh great sir thank you so much sir you will we have some positive comments back to kashina very informative excellent session thank you so much so thank you for joining us just try to keep it a bit simple though we have tried to cover the advanced parkinson's disease and these dyskinesias part but why i have not discussed certain things is because i don't want the audience to get confused so there are certain things that that cannot be that should be avoided but what i want to disc wanted to discuss was and tell you in brief about how to manage early parkinson's and now how to manage advanced parkinson's because they're both different yes yes uh so we have one more question uh dr navanee kumar is asking 60 year old patient having persistent involuntary movement in right hand with other symptoms of pd so what would you suggest the treatment so a 60 year old somebody with involuntary movements with other symptoms should be started on [Music] okay yes dr prajwal says we'll be waiting for your next lecture sure i'm also i'll also be waiting to you again [Music] take care everyone


Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly, with men being more affected. There is currently no cure for the disease, and there are no laboratory tests, biomarkers, or imaging studies to confirm Parkinson's disease. As a result, it is important for clinicians to analyze patients' motor features effectively and efficiently to diagnose cases of Parkinson's disease. Further to that, with the increasing prevalence of PD in the world, and its difficult to diagnose and cure features, it is critical to understand its pathophysiology, diagnosis, and Mx with Expert Dr. Vinit Banga (Senior Consultant, Neurology & Neurovascular Intervention). This is part -2 and you can catch up on part 1 by going to the replay section.


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