Different Methods of Diagnosis
Typical diagnosis occurs when a patient is experiencing the three prominent signs that are most evident in Parkinson’s disease: resting tremor, rigidity, and bradykinesia. Once a patient is diagnosed and is put on the medication Levodopa, if the individual does not respond to the medication but continues to show signs and symptoms of Parkinson’s disease this is referred to as Idiopathic (unknown) Parkinson’s Disease.
New methods of MRI scanning are being used to detect early signs of PD
“Conventional MRI cannot detect early signs of Parkinson's, so the Oxford researchers used an MRI technique, called resting-state fMRI, in which people are simply required to stay still in the scanner. They used the MRI data to look at the 'connectivity', or strength of brain networks, in the basal ganglia – part of the brain known to be involved in Parkinson's disease.” (University of Oxford, June 2014).
By defining a threshold level of connectivity, researchers were able to detect PD patients with 100% accuracy and non PD patients with 89% accuracy(few false positives). By testing the strength of the brain networks in the basal ganglia, diagnosis of Parkinson’s can begin at even the earliest stages of the disease. The research team hopes to take this to the next step of picking up PD before symptoms arise in the future.
Alpha-Synuclein Protein
“Alpha-synuclein is the protein, component of the lewy bodies and its accumulation in tissues helps diagnose PD in patients. Abnormal alpha-synuclein aggregation may begin in the peripheral nervous system, possibly in the nerves of the gastrointestinal submucosal region many years before motor symptoms appear. In one study, colon tissue extracted during a colonoscopy was analyzed in patients in the early stages of PD but who had not been treated for PD. Tissue samples showed that 9 out of 10 had alpha-synuclein inclusions in the tissue” (Christine, 2011a).
Screening for Biomarkers
Biomarkers is playing a very important role in diagnosing specific diseases and supporting to diagnose Parkinson’s disease to a very limited extent. A new developed technique called diffusion MRI have shown great improvement in detecting its signs and also to discriminate between the .typical and atypical type of Parkinson’s disease.
“The Michael J. Fox Foundation is using these techniques in an ongoing study of biomarkers called the Parkinson’s Progression Markers Initiative (PPMI). They are looking at movement, cognitive, and brain biomarkers in addition to blood, urine, DNA, and spinal fluid sampling in 400 newly diagnosed PD patients over a 3- to 5-year period (Christine, 2011a)”.
Typical diagnosis occurs when a patient is experiencing the three prominent signs that are most evident in Parkinson’s disease: resting tremor, rigidity, and bradykinesia. Once a patient is diagnosed and is put on the medication Levodopa, if the individual does not respond to the medication but continues to show signs and symptoms of Parkinson’s disease this is referred to as Idiopathic (unknown) Parkinson’s Disease.
New methods of MRI scanning are being used to detect early signs of PD
“Conventional MRI cannot detect early signs of Parkinson's, so the Oxford researchers used an MRI technique, called resting-state fMRI, in which people are simply required to stay still in the scanner. They used the MRI data to look at the 'connectivity', or strength of brain networks, in the basal ganglia – part of the brain known to be involved in Parkinson's disease.” (University of Oxford, June 2014).
By defining a threshold level of connectivity, researchers were able to detect PD patients with 100% accuracy and non PD patients with 89% accuracy(few false positives). By testing the strength of the brain networks in the basal ganglia, diagnosis of Parkinson’s can begin at even the earliest stages of the disease. The research team hopes to take this to the next step of picking up PD before symptoms arise in the future.
Alpha-Synuclein Protein
“Alpha-synuclein is the protein, component of the lewy bodies and its accumulation in tissues helps diagnose PD in patients. Abnormal alpha-synuclein aggregation may begin in the peripheral nervous system, possibly in the nerves of the gastrointestinal submucosal region many years before motor symptoms appear. In one study, colon tissue extracted during a colonoscopy was analyzed in patients in the early stages of PD but who had not been treated for PD. Tissue samples showed that 9 out of 10 had alpha-synuclein inclusions in the tissue” (Christine, 2011a).
Screening for Biomarkers
Biomarkers is playing a very important role in diagnosing specific diseases and supporting to diagnose Parkinson’s disease to a very limited extent. A new developed technique called diffusion MRI have shown great improvement in detecting its signs and also to discriminate between the .typical and atypical type of Parkinson’s disease.
“The Michael J. Fox Foundation is using these techniques in an ongoing study of biomarkers called the Parkinson’s Progression Markers Initiative (PPMI). They are looking at movement, cognitive, and brain biomarkers in addition to blood, urine, DNA, and spinal fluid sampling in 400 newly diagnosed PD patients over a 3- to 5-year period (Christine, 2011a)”.
Mathematical Models for Dopaminergic and Serotonergic Systems
J.A. Best and his team have created mathematical models for the serotonin and dopamine terminals. They used blood tryptophan as an input in the model and other nine substrates can also be used as an input in the model. For each differential equation that has been used to quantitate mass balance expression, “The rate of change of the concentration of a substrate is simply the sum of the rates of the reactions by which it is made minus the sum of the rates of the reactions in which it is used. For example, the concentration of 5-hydroxytryptophan, [5htp], satisfies:
J.A. Best and his team have created mathematical models for the serotonin and dopamine terminals. They used blood tryptophan as an input in the model and other nine substrates can also be used as an input in the model. For each differential equation that has been used to quantitate mass balance expression, “The rate of change of the concentration of a substrate is simply the sum of the rates of the reactions by which it is made minus the sum of the rates of the reactions in which it is used. For example, the concentration of 5-hydroxytryptophan, [5htp], satisfies:
VTPH is the velocity of the TPH reaction and VAADC is the velocity of the AADC reaction. One must specify exactly how these velocities depend on the current values of various substrates. VTPH is given by:
The first term on the right is of Michaelis-Menten form and gives the dependence of the velocity on the concentrations of tryptophan and bh4. The enzyme TPH shows substrate inhibition (Best et al., 2010a; Friedman et al., 1974; McKinney et al., 2005), which is the reason for the (trp) 2 term in the denominator. The second term on the right expresses how the concentration of extracellular 5-HT influences the rate of synthesis via the auto receptors. At normal e5-HT concentration (.768 nM) this factor equals one. As e5-HT goes up the factor can go as low as 0.5 and as e5-HT goes down, the factor can go as high as 1.5. We chose Km and Ki values from the literature and chose the Vmax so that the normal velocity of the the TPH reaction is in the range given by experiments. The form of the second factor is more speculative. Though it is certain that increasing extracellular concentrations of 5-HT inhibit synthesis via the auto receptors (Adell et al., 2002), there is relatively little information in the literature about the range of e5-HT concentrations over which the effect takes place and about the strength of the effect in the low nanomolar range.”(Best et.al, 2009,2010a,2010b).
Titcombe et.al states that, "There are lot of questions which have been unanswered regarding Parkinson’s disease. Recent studies have found two hypothesis for the question: 'Where does the tremor in Parkinson’s disease originate from'? Researchers stated that this process mainly involves central and peripheral feedback mechanisms. They stated that oscillations originate from central nervous system may be somewhere in motor control regions of the brain such as thalamus and basal ganglia."
Mathematical Model for Parkinson’s Tremor
“In the 1960’s, two articles appeared (Austin and Tsai 1962, Austin et.al; 1965) describing a model for Parkinson’s tremor based on the Van der Pol oscillator. The Van der Pol equation is of the form:
Titcombe et.al states that, "There are lot of questions which have been unanswered regarding Parkinson’s disease. Recent studies have found two hypothesis for the question: 'Where does the tremor in Parkinson’s disease originate from'? Researchers stated that this process mainly involves central and peripheral feedback mechanisms. They stated that oscillations originate from central nervous system may be somewhere in motor control regions of the brain such as thalamus and basal ganglia."
Mathematical Model for Parkinson’s Tremor
“In the 1960’s, two articles appeared (Austin and Tsai 1962, Austin et.al; 1965) describing a model for Parkinson’s tremor based on the Van der Pol oscillator. The Van der Pol equation is of the form:
...This equation is second-order, nonlinear, and depends on one parameter, α.”(1965,1962).
Coping
We must remember that this disease is more than formulas and equations, this is people's lives. If you or a loved one is suffering from Parkinson's Disease the big idea from this site we hope you can take to heart is that, you are not alone.
We must remember that this disease is more than formulas and equations, this is people's lives. If you or a loved one is suffering from Parkinson's Disease the big idea from this site we hope you can take to heart is that, you are not alone.
Researchers are learning more about this disease everyday, and as students we must remember that whatever specialty we choose to follow in the field of biomedical engineering, that the end goal is improving people's lives.
References
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Images:
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Videos:
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