Parkinson's
Introduction
Parkinson’s Disease (PD) is a neurogenic disorder associated primarily with expressed motor dysfunctions. From bradykinesia and awkward gait, to postural instability and hypomimia, PD is conceptualized so classically as an illness affecting body movement that the abnormal psychological or neuropsychological states that often accompany it, remain inconspicuous and, in some cases, vastly underreported. Major Depressive Disorder commonly presents as a comorbidity with PD, and cognitive dysfunctions, particularly in cortical areas pertaining to executive functions such as judgement and planning, are also frequent, and in need of further research. Additionally, investigations into the prevalence of acquiring Impulse Control Disorders, or associated conditions such as punding, is now underway, and reports are demonstrating these conditions to be common, despite the public’s lack of knowledge regarding them. Fortunately, recent scientific investigations into these and other detrimental effects of PD have resulted in several discoveries that could set the foundations for novel treatments to increase quality of life for individuals afflicted by PD, and, with increasing treatment options will come increasing public awareness of the vast scope of issues related to this incurable, progressive, degenerative illness.
By far the most common generalized treatment for PD is administration of the drug levodopa (L-DOPA.) L-DOPA is a precursor molecule to DA (as well as any neurotransmitter in the catecholamine class) and is necessary for synthesis of the chemical. Unlike DA, L-DOPA is small enough to permeate the blood-brain barrier. Once through the membrane, the molecule is catalyzed by the enzyme Aromatic-L-amino-acid decarboxylase into DA (3) where an increase in the neurotransmitter may help to mitigate the hypokinesic symptoms characteristic of PD. Since the 1960’s, treatment with the L-DOPA drug has been the standard Parkinson’s treatment, however recent investigations have implicated several other treatment methods as potentially beneficial. Whereas L-DOPA remains an effective treatment, it frequently leads to development of hyperkinesic side effects such as tremors. Additionally, though rare, there are instances in which L-DOPA does not prove to be effective. For these reasons, additional or alternative preventative measures must be investigated. The remainder of this site will discuss several side effects of dopamine treatment medications, and present recent research into possible practical solutions. The goal is to emphasize these potential treatment reforms, as well as to educate readers with regards to less-known clinical presentations associated with Parkinsonian treatment drugs.
By Katja Shimkin
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A Basic Explanation of Parkinsonian Neurological Deficit
A 2008 review article sponsored by Duke University Medical School describes the basis of the pathophysiology of Parkinson’s Disease, emphasizing the loss of dopaminergic neurons in two specific regions of the cerebral cortex: the ventral tegmental area (VTA), and the pars compacta. The production-site of dopaminergic neurons, the VTA maintains an extensive neuronal projection circuit, supplying dopamine (DA) to nearly the entire brain, cortex and brainstem. The second structure described in the paper is the pars compacta, one of two structures that comprise the substantia nigra, a cortical region that supplies inhibitory GABA neurons to the striatum. The striatum, or striate cortex, is the source of dopamine and glutamine neurons to the movement-regulating brain region called the basal ganglia, and is also a major contributor to the brain’s reward system. (1) Implication of the above neuroanatomical regions in the development of PD is not novel, and indeed is widely-recognized. Nevertheless, a brief description of the pathophysiology related to acquiring PD seems in order.
As a primary binder to excitatory neuroreceptors, dopamine is highly implicated in Parkinsonian pathologies, either motor or cognitive. In an unaffected brain, DA projections from substantia nigra to the striate are abundant. PD, however, is an illness predominantly induced by degeneration of such projections. Because the striate supplies the movement-controlling basal ganglia with DA, a diminished quantity of DA neurons projecting to the striatum effectually diminishes the amount reaching the basal ganglia. This accounts for the hypokinesic symptoms frequent in those who suffer from Parkinson’s: muscle rigidity, difficulties producing self-inspired movements, hypomimia, etc. Additionally, dopaminergic depletion in areas, such as the basal ganglia, related to the brain’s reward system may explain the biochemical aspect of elevated depression rates in those diagnosed with the disease. (2) nnnn FINISH THIS!!!
Section 2
Punding, a seemingly rare though perhaps merely underreported side effect of long-term L-DOPA intake, refers to the incidence of (a) severe, irrepressible, repetitive behavior(s), usually detrimental to the individual’s physical and social well-being. One case report described a 68 year-old PD patient who, after medications, developed a compulsive obsession with drumming, playing for hours every day, purchasing a recording studio for his home, and shunning social interactions, food, and sleep, in order to avoid feelings of depression and anxiety. (After six months, his medication was changed and the patient no longer felt controlled by the need to drum to achieve “wellbeing and a feeling of calmness.”) (4) A study published in 2013 analyzed the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on incidence of such a strange side effect of PD medication in Parkinson’s patients. Researchers focused their efforts specifically on the brain’s dorsolateral prefrontal cortex (DLPFC), comparing effects of left- versus right-hemisphere stimulation. (5) After delivering a series of low-frequency electrical pulses over a period of 32 minutes, to a sample of patients who had demonstrated punding behaviors, it was found that score on a Punding Scale decreased after stimulation over the right of left DLPFC. After right-sided stimulation, the score remained lower after a second measurement. At third measurement, however, regardless of hemisphere, scores were not significantly different from initially Punding Scale scores. This demonstrates rTMS over the DLPFC, especially when directed at the right hemisphere, has the potential of minimizing punding behaviors. The authors conclude by suggesting a patient undergoing repeated rTMS for several consecutive days may experience a longer-duration of benefits from the treatment. (5)
Section 3
Include some current research, with at least one figure showing data.
Conclusion
References
Authored for BIOL 291.00 Health Service and Biomedical Analysis, taught by Joan Slonczewski, 2016, Kenyon College.
