Parkinson's Disease (Shaking Palsy) - Clinical Presentation and Pathophysiology

hello in this video we're going to talk about Parkinson's disease um which is a neurodegenerative disease about 0.3% of the population over the age of 40 um has this um disease it's about 7.5 million people worldwide so let's look at the firstly signs and symptoms of Parkinson's and here I'm drawing a patient um who shows who presents with tremors shaking and he presents like this due to a condition called Parkinson's disease that affects the brain the Cardinal features of Parkinson's disease there four these include Tremors rigidity Brady kinesia postural instability there are other features which

affect the cranial facial areas which include hypomimia which is basically decrease in facial expression dysphasia hypophonia reduction in uh basically the tone of the voice volume Vis uh other features include visual problems such as blurred vision and eyelid opening aaia um other features also include gate you can have shuffling festations and freezing so all these signs and symptoms are a result of um uh problems that occur within the brain particularly in an area of the brain known as the basil ganglia so let's just quickly revise some important anatomical structures of the brain so here we

have the phonic which is an important part of the lyic system we have the hippocampus which is for memory the amydala for emotions but we will mainly concentrate on this yellow uh structure here which is known as the basil ganglia or the basil nucleus medially to the basil ganglia is the thalamus which essentially is a connection between the cortex and the brain stem spinal cord so again Parkinson's disease is a result of problems that occur within the basil ganglia or the basil nucleus because this area is responsible for um muscle tone as well as the

ease of um movement so to it helps in a smooth movement and learned movement patterns so let's just take a cross-section chronal section of the brain here and look at the basil gangle in a bit more details and it's comp components so here we looking at a section of the brain here in green is the thalamus just to orientate where we are all these structures in yellow here they are part of the basil ganglia so basil ganglia is made up of the C nucleus C pamin pamin the Globus paladis of which we have an external

and internal part we also is made up of the nucleus accumbens which I have not drawn here um and we have also have the subthalamic subthalamic nucleus and the substantia which is consists of two parts and just to complete this image we all we have the amig um the amydala here as well as the hippocampus so we will mainly Focus again on the basil ganglia which is disrupted in Parkinson's disease so what does the basil ganglia do so let's just have a quick General overview of what it does so here again we have the brain

and this yellow structure is a basil ganglia essentially what happens is um the cortex when it wants to in when it when it wants to initiate a movement it will send signals first to the basil ganglia and the basil ganglia will send signals back to the CeX particularly the Moto cortex and then when the signals are sent back to the Moto cortex the M cortex can then you know initiate these signals uh send the signals down the spinal cord um and then you know out through the ventral Horn of the spinal cord to that skeletal

muscle to you know initiate a smooth controlled movement okay now let's uh look at that in a bit more detail so again the cerebral cortex um is it wants to initiate a voluntary movement it will it will first send signals to the Bas Bas ganglia and the basil ganglia will help in the subconscious control of sub skeletal muscle tone as well as the coordination of learned movement patterns this information will then be sent back to the cereal cortex through a loop it will be sent to the thalamus first and then the thalamus will send this

info to the cerebral cortex the cerebral cortex will then um send the movement signals the smooth controlled movement signals down the spinal cord to the skeletal muscle and thus we have a normal movement pattern two important parts in this diagram the input from the cerebral cortex to the basil ganglia and the output from the basil ganglia to the thalamus back to the cortex in Parkinson's disease the output number two there's a problem in the output and thus we do not have a normal controlled movement pattern it is not smooth so now let us go back

to the big diagram and learn about the interconnection that occur within the basil ganglia and how and the disruption that occurs and how this results in Parkinson's disease so in this diagram um we're going to look at all the components of the basil ganglia so to start the kodate nucleus and kodate pamin is also known as the kodate striatum so here the rectangular structure I'm drawing is the cordate striatum this is the cortex and all these other structures here are part of the basal ganglia we have the substantial nigras compacta the Globus palus internal the

substantial Nigro pars reticula the Globus paladis external the subthalamic nucleus and the thalamus now I'm going to start drawing the interconnections that occur within this region but firstly I I want to I want you to uh learn three main points the input from the cortex to the basil ganglia is uh to the striatum to the cordate striatum first so the input is is to the cordate strium the output from the basil ganglia occurs in the Globus paladis interna that's point two so the Globus palus interna is the output from the baso ganglia to the thalamus

and then the thalamus will then send this information to the cortex back to the cortex in that Loop and this is three the cortex will then send this information to the skeletal muscle down the spinal cord to to you know to cause a smooth movement pattern coordinated movement pattern so those are the three main points the input to the basil ganglia the output from the basil ganglia and then the output from the from the cortex again to the muscle now within the basil ganglia there's a lot of interconnections happening between the glutaminergic neurons which are

the excited neurons as well as the gabanergic neurons which are your inhibitory neurons but the most important thing in uh in this diagram are is within the substantial nraas compacta because here we have dopaminergic neurons that arise and these dopaminergic neurons they release dopamine into the cordate striatum so dopamine can bind onto two types of receptor D1 dopamine 1 or dopamine 2 and depending on which receptor it binds to it it is either excitatory or inhibitory so if dopamine binds onto D1 receptor it is excitatory if so it will stimulate that neuron if dopamine binds

to dd2 receptors dopamine will inhibit that neuron so if we were to follow it step by step uh the dopamine nergic neurons releases do dopamine dopamine binds onto the D1 receptor which is excitatory so it will stimulate the gabanergic neuron here and it will directly inhibit this gab gabanergic neuron allowing the thalamus to send signals to the cortex so thus the cortex can um you know um send signals to the skeletal muscle for a controlled movement pattern so that is what occurs normally but unfortunately in pinson's disease there is there's not much dopamine the dopamine

nergic neurons die so in Parkinson's disease you have a reduced uh dopamine in the substantial and the pathogenesis probably involves apoptosis or necrosis of dopaminergic neurons and it is it is a result of the death of these neurons can be due to uh protein misfolding AG aggregation and toxicity it can be due to defective proteolysis it can be due to mitochondrial dysfunction or oxidative stress these are all theories regardless of the cause the result is that we have reduced dopamine in the in this area in the basil ganglia okay now let's go back to the

diagram and look at what happens if we have reduced dopamine if we have reduced dopamine dopamine does not bind onto the D2 receptor which normally inhibits this gabanergic neuron thus the gabanergic neuron here is now overactive and secretes Gaba which inhibits the second gabanergic neuron because this gabanergic neuron is now inhibited it cannot inhibit the glutaminergic neuron in the subthalamic nucleus and so the subthalamic nucleus glutaminergic neuron neuron will secrete glutamate which will stimulate this gabanergic neuron in the Globus palus interna similarly because we have no dopamine the dopamine does not bind onto the D1

receptor and so the gabanergic neuron that normally inhibits uh the globous paladis interna neuron is not stimulated and as a result we have a overactive um gabanergic neuron from the Globus palus interna to the thalamus so we have excessive inhibitory input to the thalamus Thalamus inhibition causes suppression um of the theal corticos spinal pathway and because of this um the signals that the basil ganglia should have sent back to the cortex doesn't doesn't really happen and so as a result when the when you want to initiate a movement it's not smooth coordinated controlled and and

thus you result in thus it results in the clinical manifestations of Parkinson's disease I hope that all made sense now let's look at the pathology of Parkinson's disease so let's zoom into the substantial area here which is which can be which is basically located on the midbrain here's a cross-section of the midbrain and let's compare pinson's disease um uh substanti nagra to the one of a normal patient what we see in Parkinson's disease is we see demyelination neuronal loss and gliosis within the substantial another pathological Hallmarks is uh the presence of Louis bodies within the

Soma of the neuron so here we have the S of the neuron and this blue structure here are Louis bodies and Louis IES are round eopc intracytoplasmic occlusions in the nucleus uh in the nuclei of the neuron um the Louis bodies are made up of mainly um Alpha sincan proteins ubiinsulin now let's talk about the risk factors as well as the protective factors of Parkinson's disease so the risk factors of Parkinson's disease um include um family risk factors there are genetic risk factors which include GBA cnca um lurk to park 2 and pink one as

well as there's shown that pesticides can cause Parkinson's disease protective factors include smoking coffee vigorous exercising as well as the use of non-steroidal anti-inflammatory Dr drugs so that concludes this video on Parkinson's disease we looked at the signs and symptoms we looked at the some neuro anatomy of the basil ganglia we looked at the function of the basil ganglia as well as what occurs in Parkinson's disease and then we looked at the the pathophys as well as the pathology and the risk factors and protective factors thank you for watching I hope you enjoy this video