By: Keshav Suresh Confusion. Muscle stiffness. Loss of memory. Trembling. These are all the telltale symptoms that people associate with Parkinson’s disease (PD). Parkinson’s is the second most common neurodegenerative disease in America, and like many other neurodegenerative diseases, there is so little known about its causes. All we know is how the affected brain looks and how a person acts after developing Parkinson’s. There is no simple hormone level to test or a scan to perform that can reliably diagnose Parkinson’s; instead, doctors need to rely solely on medical histories and arbitrary neurological tests with results that can vary wildly from doctor to doctor. For any disease, the earlier a diagnosis is made, the more effective any possible treatment is--which is where Dr. Nicolas Phielipp and his team come in. Dr. Phielipp is starting a clinical study at the University of California, Irvine using a series of tests and tasks to build on past studies done on neurodegenerative diseases. He will be testing for the sterility assurance levels (SAL) by using Quantitative Electroencephalography (qEEG), and performing dopamine transporter (DaT)-SPECT imaging on patients with PD. Another part of his protocol is making the patients do a dual task. He hopes to recruit fifteen patients: ten with Parkinson’s, and five healthy control subjects. He hopes to find some type of biomarker or serological sign that a patient will develop Parkinson’s before they ever actually display clinical symptoms. One of the most common methods used to diagnose and measure the severity of Parkinson’s and other neurodegenerative diseases is the double task. This involves directing the subject to do a physical and mental activity simultaneously. For example, one study made patients walk while calculating subtraction problems in their head [1]. Patients with Parkinson’s struggle with these type of tasks because it requires using multiple parts of the brain and since their neurons are breaking down, they tend to do worse on one or both of the tasks than the average person. The subjects will be graded on a scale to measure how severe their condition is. The next part uses transcranial magnetic stimulation (TMS) to measure the output of cholinergic circuits which are associated with memory, mood, and emotion. It has been found that patients suffering from PD have cholinergic circuits with vastly reduced output which corresponds with the decreased cognitive function typical of Parkinson’s [2]. By using TMS and analyzing different circuits and the speeds of these circuits, Dr. Phielipp hopes to identify if there is some sign that these circuits will lose function, which correlates to Parkinson’s. Another test Dr. Phielipp will be using is qEEG, or Quantitative Electroencephalography, which is when the brain is stimulated with electrical signals and then the pathways that those signals take are analyzed with a computer. Previous studies have analyzed different types of wavelengths in patients with various neurodegenerative diseases and have found some correlations. It was discovered that patients with abnormally high or low background rhythm frequencies more commonly have dementia. Similarly, dementia patients have also been found to have high theta frequencies [3]. Dr. Phielipp hopes to use this data and analyze qEEGs for all the subjects in hopes of finding some commonality to be able to predict the likelihood of someone developing Parkinson’s Disease. The final measurement will be a DaTSPECT, which is used to detect the presence of dopamine transporters in the brain. SPECT stands for single photon emission computed tomography. It is a form of nuclear medicine where a radioactive tracer is introduced to the part of the body that is to be studied (in this case the brain), and gamma rays are used to track the movement of the tracer throughout the body. The DaTSPECT follows the nigrostriatal pathway, which is a dopaminergic pathway connecting substantia nigra to the putamen, the part of the brain that regulates learning and movement. Since this is where a lot of dopamine goes through for the brain, this is what is affected first by Parkinson’s. After scanning the brain there was a lower DaT uptake in the putamen, hindering its function. The first step in medicine has always been diagnosis, and the more that doctors know and the more time they have to work with, the better chance they have of finding a treatment. It requires comprehensive studies like Dr. Phielipp’s and lots of trial and error for any progress to be made in the medical world. References
1.Duval, Christian, Abbas F. Sadikot, and Michel Panisset. 2006. "Bradykinesia in Patients with Essential Tremor." Brain Research 1115.1: 213-16. 2.O'Shea, Simone, Meg E Morris, and Robert Iansek. 2002. "Dual Task Interference During Gait in People With Parkinson Disease: Effects of Motor Versus Cognitive Secondary Tasks." Physical Therapy 82.9: 888-897. 3.Nardone, Raffaele, Jürgen Bergmann, Francesco Brigo, Monica Christova, Alexander Kunz, Martin Seidl, Frediano Tezzon, Eugen Trinka, and Stefan Golaszewski. 2012. "Functional Evaluation of Central Cholinergic Circuits in Patients with Parkinson’s Disease and REM Sleep Behavior Disorder: A TMS Study." Journal of Neural Transmission J Neural Transm 120.3: 413-22. 4.Klassen, B. T., J. G. Hentz, H. A. Shill, E. Driver-Dunckley, V. G. H. Evidente, M. N. Sabbagh, C. H. Adler, and J. N. Caviness. 2011. "Quantitative EEG as a Predictive Biomarker for Parkinson Disease Dementia." Neurology 77.2: 118-24. 5.Mascalchi, Mario, Alessandra Vella, and Roberto Ceravolo. 2012. "Movement Disorders: Role of Imaging in Diagnosis." J. Magn. Reson. Imaging Journal of Magnetic Resonance Imaging 35.2: 239-56.
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