 Parkinsonism which is also known as a Paralysis Agitance is a disorder in which is Substantial Nigra Pars Compacta component of the basal ganglia. The neurons which are present here the Substantial Nigra Pars Compacta Dopaminergic neurons they get destroyed and with the destruction of these dopaminergic neurons what we get is a Hypokinetic disorder very important term hypokinetic disorder known as Parkinson's disease. So to understand that how this Parkinsonism is occurring and what are the physiological basis of signs and symptoms of Parkinson's disease we need to understand little bit basics about the basal ganglia circuit. So let us quickly see what is this basal ganglia circuit. So here this diagram is showing the cortex basal ganglia and thalamic cortex loop. So signals from cortex actually stimulate the stratum and from there you see there are two pathways known as the direct pathway, indirect pathway which are going towards the thalamus and then thalamus is having a excitatory connections with the cortex. So see the direct pathway what is happening that stratum is basically inhibiting the Globus Pallidus internal segment and Globus Pallidus internal is in turn inhibiting the thalamus. So basically there is inhibition of the inhibition. Okay Globus Pallidus internal is inhibiting the thalamus. So input from the stratum when it inhibits the Globus Pallidus internal it will not be able to inhibit the thalamus and hence thalamus will be able to send the excitatory signals towards the cortex. So due to this direct pathway signals to the cortex are facilitated. So we say the direct pathway actually facilitates movement. On the other hand if you see the indirect pathway there are three negatives here right. So in the direct pathway two negatives and two negatives make a positive. In the indirect pathway three negatives. So basically in this indirect pathway actually inhibits movement. Direct pathway facilitates movement. Indirect pathway ii inhibits the movement. Fine now you see the effect of the dopaminergic neurons which are coming from the substantia nigra pass compacta. Dopamine facilitates the direct pathway. Okay so dopamine further facilitates the movement which is being caused by the direct pathway and dopamine inhibits the indirect pathway. So by facilitating the direct pathway and inhibiting the indirect pathway we said the indirect pathway is for inhibiting movement. So dopamine is further inhibiting this indirect pathway. So this also will facilitate movement. In short we can say that the role of dopamine is to facilitate the movement by facilitating the direct pathway and inhibiting the indirect pathway. Fine now let us come to the Parkinsonism features. So what happens in Parkinsonism as we said before that these dopaminergic neurons are lost. So if this dopaminergic neurons are lost dopamine will not be able to facilitate the movement and if dopamine is not able to facilitate the movement then this input from thalamus to the cortex is going to reduce right. So the facilitatory signals to the cortex are going to reduce and this will lead to hypokinetic disorder or one of the features of Parkinsonism is a kinesia. So there will be inability to initiate movement. So with this let us see all the features of the Parkinsonism. So first feature as I said is a kinesia that is the inability to initiate movement or there is brady kinesia also that is extreme slowness of movement that is what happens that the person has inability to initiate the movement and it requires a lot of mental effort from the patient to that it concentrates a lot to initiate a movement and when he does initiate the movement is very slow so that is known as brady kinesia. Then there are other cardinal features of Parkinson's disease them being a cog wheel rigidity, cog wheel rigidity and there is resting tremor. So what are these resting tremors? So what are these basically resting tremor is tremor in the resting state that means when there is no movement going on in that case we see certain tremors and the characteristics of this tremors are that they obviously occur in resting state movement is not going on and they have a frequency of 8 hertz approximately 8 cycles per second and why do they occur? The exact reason is not much known but they say that it is due to increased oscillations in the basal ganglia circuit. So you see that it was a negative feedback circuit which was operating in the basic one you saw right. So there was cortex then to basal ganglia and basal ganglia was having inhibitory input to the thalamus and which was having an excitatory input to the cortex. So because of this negative feedback circuit when this is gone then there is increased oscillations in the circuit that leads to the resting tremors. Then what is this cog wheel rigidity? Cog wheel rigidity is that when we try to test the tone of the muscles you might be knowing that tone is tested by passive movement of the muscles. So when we try to test the tone by passive movement of the muscles the tone is interrupted in between like a cog wheel. So in between it gives way in jerks that is known as cog wheel rigidity and why is cog wheel rigidity occurring? This is because the differential effect of basal ganglia on the agonist muscle action and the antagonist muscle action. Actually you see the direct pathway and indirect pathway why do they exist? They exist because suppose the direct pathway will facilitate movement for the biceps contraction if we want to flex our muscles we want biceps to contract. So there will be biceps contraction. On the other hand similarly we want the inhibition of other muscles. So for that we want the antagonist to be inhibited. So this indirect pathway works there and causes the inhibition of the antagonist contraction. So that is how the basal ganglia is helpful in facilitating movement. So in basal ganglia disorder, Parkinsonism what happens that agonist is activated less okay and antagonist is inhibited less. Agonist is activated less and antagonist is inhibited less and that is the reason that we get cog wheel rigidity. Coming to other features the person has gate problem. What gate problems he has? He has something known as festinent gate. And he walks with shuffling steps. Why so? See what happens we are telling that he is having a problem in initiation of the movement. So because of that because of impaired initiation his trunk. So let us just line diagram will make of body. So suppose there is a leg and this is the trunk of the person right. Sorry for the bad drawing but like that. His trunk bends a little forward okay. Because of this center gravity you see bends little forward. So he tries to catch up the center of gravity because body has to balance isn't it. So he tries to catch up the center of gravity by moving his legs fast. So this type of posture while gate is known as festinent gate. And this fast movement of steps is known as shuffling steps. Then there are other features that all because of the hypokinetic disorder because of the echinacea there is masked facies. That is lack of any facial expression masked facies. There is a decreased arm swinging because he is not initiating any movements on his own right. So lack of fidgety action what we do like when we are sitting some of other movement we are continuously making. So there is lack of fidgety action as well right. Then one of the function of diesel ganglia is scaling. That means suppose if I am writing then how much the size of the letter should be right. So that is a scaling. Now in this Parkinsonism what happens that the writing becomes very small. So that is known as micrographia because the scaling function of the basal ganglia is affected. Now these are all motor disorders but apart from these there are other features of basal ganglia which also develop over time. And these include cognitive impairment. Okay so that is also important we should remember that basal ganglia doesn't mean Parkinsonism doesn't mean that only there will be motor involvement. There can be cognitive impairment, dementia then mood disorder will develop the person will have sleep difficulty okay. So mood disorder then sleep difficulty will be there and there will be certain autonomic disturbances as well because the pathology which is there it is affecting different sides of the brain. So we get motor as well as non-motor features in Parkinsonism disease. Now let's see the treatment aspects. What will be the physiological basis of treatment? So we know that dopaminergic neurons have been destroyed. So we need to increase the dopamine in the stratum right. So what to do? Give the dopamine right but it is not given just like dopamine. There is a formulation that is L-dopa. It is given as L-dopa because this L-dopa crosses the blood-brain barrier and in the brain it is converted to dopamine. So that is first form of treatment L-dopa. Then along with L-dopa is added decarboxylase inhibitors. Decarboxylase inhibitors. What it does is that this decarboxylase inhibitor prevents the peripheral conversion of L-dopa to dopamine. So L-dopa will not be converted to dopamine in periphery. Rather most of the L-dopa crosses the blood-brain barrier and there is converted to dopamine if decarboxylase inhibitor is added. Then next is dopamine agonist. Dopamine agonists basically are used in advanced phase of the disease where the person has lost the ability to synthesize, store and release dopamine from L-dopa. So then dopamine agonist are given. Third is adding compt inhibitors, CUMT inhibitor to the L-dopa treatment because when this decarboxylase inhibitor is giving there is another pathway by which L-dopa can be metabolized in the periphery. So this compt inhibitor prevents that. Then fourth comes the mauve inhibitor. Monamine oxidase B inhibitor and this prevents the cerebral degradation of dopamine. Understanding so this is preventing the peripheral degradation of L-dopa. Then compt inhibitor also prevents the peripheral degradation of L-dopa. Mauve inhibitor prevents the central degradation of dopamine so that more dopamine is available centrally. So that is mauve inhibitor. You see all the strategies are there to make dopamine available. Then fifth is use of anticholinergic drugs. What are these anticholinergic drugs? Actually we have not seen in the circuit of basal ganglia but basal ganglia also has a spiny neurons which release acetylcholine and they say that it is the balance between the acetylcholine and dopamine that we get adequate functioning of the basal ganglia. So these anticholinergic drugs basically restore this balance between the acetylcholine and dopamine and this is especially useful for patients who are having severe tremor. So these anticholinergic drugs are used but remember they are not used in old age. So that's all for physiological basis of signs and symptoms and treatment of Parkinsonism. 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