foreign [Music] Parkinson's disease is a neurodegenerative condition affecting dopaminergic neurons in the brain leading to Associated motor symptoms neurodegeneration means a progressive irreversible loss of neurons and in Parkinson's disease it is mostly the dopamine-producing neurons in the substantial that are lost for us to move signals are generated by the cerebral cortex that then pass through the motor pathways and Lead it to contraction of our muscles and ultimately movement however this process needs to be regulated which is primarily the job of the basal ganglia the substantia is a part of the basal ganglia which are a group of nuclei in the brain altogether these are the striatum which includes the putamen and chordate nucleus amongst others the Globus pallidus subthalamic nucleus and of course the substantia normally there are two main Pathways the direct and indirect pathway the direct pathway is an excitatory pathway that facilitates movement the motor cortex sends excitory signals via glutamate to the striatum the striatum sends inhibitory signals to the Globus pallidus internus and sanction pass reticulata via Gaba these two both release Gaba which normally inhibits Thalamus so in this pathway there is inhibition of the inhibition on the thalamus giving an overall increased activity of the thalamus which promotes movement the indirect pathway is instead an inhibitory pathway that's purpose is to terminate movement in this case there is an inhibitory Gaba signal from the striatum to the Globus pallidus externus the Globus pallidus externus normally inhibits the subthalamic nucleus which normally stimulates the Globus pallidus internus this means that the indirect pathway increases the inhibitory effect of the Globus pallidus internus on the thalamus and so there is less signal from the thalamus and so there is less movement in Parkinson's there is a gradual degeneration of neurons within the substantia past compactor these neurons release dopamine to the striatum in the striatum there are direct pathway neurons that have D1 dopamine receptors and are excited by dopamine and indirect pathway neurons that have dopamine D2 receptors and are inhibited by dopamine overall this means dopamine released from the past compactor increases Movement by stimulating the direct pathway and inhibiting the indirect Pathways activity so when these neurons are lost the opposite occurs there is less stimulation of the direct pathway and less inhibition of the indirect pathway meaning an overall reduction in movement it is thought that the degeneration of these neurons is due to accumulation of Alpha's nuclein a protein involved in regulation of the synaptic vesicles and release of neurotransmitters this is the same protein accumulation found in Lewy Body dementia which is why the two are believed to be closely linked when around 50 percent of the total neurons are lost the symptoms develop which unsurprisingly are largely linked to movement bradykinesia which means slow movement is a core feature of Parkinson's disease rigidity is another core feature meaning a stiffening of the muscles the two types in Parkinson's are described as cogwheel rigidity which means small start and stop movements like a gear the second type of rigidity is lead pipe rigidity where there is an increased resistance throughout the range of motion a combination of rigidity and bradykinesia is what gives the mask-like face in Parkinson's disease known as hypommia another feature are Tremors in particular a pill rolling Tremor given its name because it affects the index finger and thumb making it resemble rolling a pill Tremors in Parkinson's disease also tend to disappear during movement and reappear at rest known as resting tremors gate is often affected patients will take several steps to turn small steps with no heel strike or toe off often called a shuffling gate generally Parkinson's disease patients are at an increased risk of Falls collectively these signs and symptoms are known as parkinsonism and Parkinson's disease makes up around 80 percent of cases however there can be other causes such as drug-induced parkinsonism multi-system atrophy Progressive supranuclear palsy and normal pressure hydrocephalus other symptoms seen in Parkinson's disease can include autonomic disturbance like hyper salivation constipation and incontinence and varying degrees of cognitive impairment can also be present the reasons why neurons are lost in Parkinson's disease are not clear and most cases are idiopathic meaning no specific cause is found it is believed that there is a genetic link as first degree relatives seem to have twice the risk of others and between 10 and 15 percent of cases are believed to be familial with a mixture of both autosomal dominant and recessive inheritance patterns environmental factors are also thought to increase the risk of Parkinson's including living in rural areas which may be due to exposure to Industrial or farming chemicals as well as infections including Encephalitis age seems to be the largest risk factor the mean age of onset of Parkinson's disease is 60 however it is estimated that 5 to 15 percent of cases actually manifest before the age of 40. it is estimated that one percent of people over the age of 60 have Parkinson's disease it is also slightly more common in males than it is in females the diagnosis is mostly clinical as there is no specific laboratory or Imaging tests available there are a new set of criteria called the movement disorder Society Parkinson's disease criteria these require parkinsonism meaning bradykinesia and one of resting Tremor or rigidity and on top of that there must be two supportive criteria no absolute exclusion criteria and no red flags the supportive criteria examples are an improvement in symptoms with dopaminergic treatment or levodopa-induced dyskinesia exclusion criteria could be parkinsonian features limited to the lower limbs for more than three years or treatment with dopamine receptor blockers coinciding with the symptoms red flags could be a rapid progression of gait impairment symmetrical parkinsonism or severe autonomic failure the full criteria are quite extensive but I'll leave a link in the description a DAT scan or radioactive isotope is injected that binds dopaminergic neurons followed then by a single Photon emission computed tomograph scan can be done to highlight areas of dopaminergic neuronal loss but this is not widely available although Parkinson's disease does not have a cure there are options to combat the symptoms medications are used to improve the quality of life although they do not generally slow down the progression increasing dopamine in the central nervous system is the goal however dopamine itself cannot be given as it does not cross the blood-brain barrier whereas levodopa a precursor to dopamine can the problem however is that levodopa is broken down peripherally by the enzyme Doper decarboxylase and therefore an inhibitor like a Carbidopa is often given to increase the amount of levodopa reaching the brain primipaxel andropineral a dopamine agonists selegeline is a monoamine oxidase B inhibitor where monoamine oxidase B breaks down primarily dopamine and the manzadine can be used as it increases dopamine synthesis and reduces its reuptake tall Capone and n-tacopone are cateical o methyl transferase Inhibitors which is also an enzyme that breaks down lever dopa but these have been associated with liver toxicity initially medication May treat the symptoms well however as time goes on there is less of an effect and the on off phenomenon almost inevitably appears with the use of levodopa over time the window for controlled symptoms known as the on phase gets tighter while off is a state of rigidity and uncontrolled symptoms the switch from on to off and vice versa can happen quickly like the change of a light switch this kinesias are involuntary movements that are a side effect that can occur when patients flip between on and off known as diphasic dyskinesia it can also occur following levodopa medication giving Peak dopamine levels known as Peak dose dyskinesia in patients who no longer gain a benefit from medication deep brain stimulation could be an option where a pulse generating device like a heart pacemaker is placed under the skin near the clavicle with electrodes connected to areas of the basal ganglia to improve function