Parkinson’s Disease Is Associated With Degeneration Of The

The Cerebellum And Dyskinesia

Chronic dopamine replacement therapy in patients with Parkinsons disease is commonly complicated by involuntary movements known as levodopa-induced dyskinesia . The neural mechanisms of levodopa-induced dyskinesia are still partially obscure, but levodopa-induced dyskinesia has been considered to be the consequence of an abnormal activity pattern in the striato-thalamo-cortical loops, which in turn induces the excessive disinhibition of thalamocortical neurons and overactivation of cortical motor areas . Recent studies suggested that the cerebello-thalamo-cortical circuit also contributes to the development of levodopa-induced dyskinesia. Deep brain stimulation of the subthalamic nucleus or globus pallidus, the surgical procedures that alleviate levodopa-induced dyskinesia , was reported to modulate neural activity or metabolism in the cerebellum . In a PET study on patients with advanced Parkinsons disease undergoing stereotactic pallidal surgery , the level of binding potential of cerebellar sigma receptors did not correlate with the Hoehn and Yahr stages, or Unified Parkinsons Disease Rating Scale, but a positive correlation was seen between the binding potential and the preoperative levodopa-induced dyskinesia severity score, giving evidence that the cerebellum may be involved in the genesis of dyskinesia.

About The Medical Reviewer

Dr. Spiegelman received his PhD in biochemistry from Princeton University in 1978, and completed postdoctoral work at Massachusetts Institute of Technology. In 1982, he joined DFCI and was promoted to professor in 1991. His research focuses on cell differentiation, cellular metabolism, and genetic factors involved in obesity and diabetes.

Recognizing Other Causes Of Parkinsonism

Although the symptoms and signs of Parkinsons disease are fairly specific, a significant fraction of patients with parkinsonism do not have PD.

In an epidemiologic study of patients with parkinsonism, Schrag et al found that

• 6% had atypical but non-specific features
• 2.5 % had progressive supranuclear palsy
• 2% had dementia with parkinsonism
• 1.7 % had multiple system atrophy

Identifyingpatients withatypical parkinsonism is important sincethese patients

• respond less reliably to dopaminergic agents,
• do not respond favorably to surgical treatments of PD, and
• develop additional clinical problems.

Atypical parkinsonism should be considered particularly

• in patients with poor dopamine responsiveness
• early loss of balance

Medication-induced Parkinsonism

Although tremor and postural instability may be less prominent, this condition may be indistinguishable from PD. Medications frequently associated with the development of parkinsonism include:

The parkinsonism usually resolves after some months after discontinuing the offending medication.

Progressive Supranuclear Palsy

Characteristic of PSP is the early onset of

• eye movement problems

There is no specific treatment for PSP. Dopaminergic treatment should be tried but often offers little benefit. Supportive measures such as speech therapy, physical therapy and antidepressants may help.

Corticobasal Degeneration

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What Are The Symptoms

The best-known symptoms of Parkinson’s disease involve loss of muscle control. However, experts now know that muscle control-related issues aren’t the only possible symptoms of Parkinson’s disease.

Motor-related symptoms

Motor symptoms which means movement-related symptoms of Parkinsons disease include the following:

Additional motor symptoms can include:

• Blinking less often than usual. This is also a symptom of reduced control of facial muscles.
• Cramped or small handwriting. Known as micrographia, this happens because of muscle control problems.
• Drooling. Another symptom that happens because of loss of facial muscle control.
• Mask-like facial expression. Known as hypomimia, this means facial expressions change very little or not at all.
• Trouble swallowing . This happens with reduced throat muscle control. It increases the risk of problems like pneumonia or choking.
• Unusually soft speaking voice . This happens because of reduced muscle control in the throat and chest.

Non-motor symptoms

Several symptoms are possible that aren’t connected to movement and muscle control. In years past, experts believed non-motor symptoms were risk factors for this disease when seen before motor symptoms. However, theres a growing amount of evidence that these symptoms can appear in the earliest stages of the disease. That means these symptoms might be warning signs that start years or even decades before motor symptoms.

Non-motor symptoms include:

Stages of Parkinsons disease

Identify The Cause Of The Pain

The first step in treating pain is to try to identify the cause. As I noted in the last essay, there are many different causes of pain for people with PD. If we look at the most common pain problems, low back and neck pain, we can see that there are many different causes for each. Many doctors order x-rays of the spine for these conditions, and they may be needed. The main problem with x-rays of the spine is that they always show arthritis, which is because virtually everyone over the age of 60 has arthritis in the spine. Whether thats the cause of the pain or not is usually not clear.

However, x-rays will show if theres a compression fracture , or a tumor. Since older women frequently develop compression fractures even without a fall, this can be important because we know then that the pain is likely severe, but time limited, and will resolve in a month or two. This makes it easier to treat with strong medication, like narcotics, because there is less concern for addiction. X-rays do not show discs, but disc herniation is much less common in older people so its of less concern.

Physical Therapy

Alternative treatments

Chiropractors focus entirely on spine pain and may be very helpful. Since many medical doctors are not very familiar with PD, I assume that many chiropractors probably arent either. Therefore it will be helpful to find one who is familiar with PD. Probably the best way to do this is through a Parkinsons Disease support group in your area.

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Collect Other Documentation Supporting Disability Due To Degenerative Disc Disease Because You May Need It

Many people that apply for SSD with back issues are initially denied benefits. This is especially true for those under the age of 50. Additional documentation can help fortify your claim, including any evidence that documents your specific symptoms and the types of common job functions they prevent you from performing. Use the following evidence to your advantage:

• Statements from your former employer or a human resources representative,
• Records of sick days, short term disability leave, and family medical leave from your former employer,
• Information in the disability application,
• A formal statement or report from your doctor, summarizing your condition and its effects on everyday activities, including employment-related activities.

Other items that may be useful as part of your appeal hearing include job descriptions, performance evaluations from work, and formal statements from family members or others that can attest to your daily limitations and your common need for assistance in completing everyday tasks.

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Surgery For Parkinson’s Disease

At one time, surgery was reserved for use in patients with early-onset Parkinson’s disease who became disabled in their prime working years. However, techniques have advanced so rapidly that surgery is now considered an option even in elderly patients as long as they meet medical screening criteria, including failure to respond to available medications and absence of cardiopulmonary risk factors for surgery. It is essential to select a neurosurgeon who is part of a movement disorders team with considerable experience in performing the surgical procedures used to treat Parkinson’s disease.

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Results From The Study

The study was based in Taiwan and analyzed more than 20,000 individuals. About half of the people in the study were diagnosed with age-related macular degeneration. The other half did not have AMD. These individuals were followed for about five years.

After adjusting for other factors, researchers found that men and women who had been diagnosed with AMD had a higher risk of developing Parkinsons disease over the 12 years this group was followed.

Incidence Of Parkinsons Disease

Its estimated that approximately four people per 1,000 in Australia have Parkinsons disease, with the incidence increasing to one in 100 over the age of 60. In Australia, there are approximately 80,000 people living with Parkinsons disease, with one in five of these people being diagnosed before the age of 50. In Victoria, more than 2,225 people are newly diagnosed with Parkinsons every year.

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Loss Of Dopaminergic Neurons And Their Projections In Pd

The involvement of the nigrostriatal dopaminergic system in PD was noted as early as neuropathological studies detected the loss of melanin-containing dopaminergic neurons in the SN of affected patients . The extent of neuronal loss in the SN by the time of clinical diagnosis was subject of several subsequent studies: While many reviews repeatedly state that first motor symptoms appear after 50% of SN dopaminergic neurons are lost , comprehensive clinico-neuropathological studies used regression analysis to more precisely determine the loss of dopaminergic neurons at the time of symptom onset. Fearnley and Lees estimated the percentage of lost pigmented SN neurons at symptom onset by 31%. Subsequent stereological analyses provided similar results extrapolating the number of remaining pigmented SN neurons to the time of motor symptom onset to about 70% . In summary, neuropathological-clinical correlations suggest that initial motor signs in PD occur as early as around 30% of total SN neurons are lost.

Treatment For Degenerative Disc Disease

Degenerative disc disease treatment includes occupational or physical therapies, either or both can be used as a treatment. Moreover, special exercises, medications, surgery or losing weight can be used.

It is important to understand all types of treatment that helps relieve chronic pain, though: traditional pain treatment options and remedial pain treatments.

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Coping With Alzheimers And Parkinsons Disease

Living with both Alzheimers disease and Parkinsons disease is extremely challenging. The dementia of Alzheimers combined with the movement effects of Parkinsons can make self-care especially difficult.

Rivastigmine is the only medication that is specifically approved for the treatment of Parkinsons dementia. Additionally, you may need medication for the motor symptoms of Parkinsons disease and medication to help with other symptoms, such as dry skin.

Neurite Degeneration In Human Stem Cell Models Of Pd

The opportunity to model PD by reprogramming patient derived cells into induced pluripotent stem cells and differentiating them into neurons recently advanced the availability of human cellular models of PD. Human dopaminergic neurons of sporadic and LRRK2 PD patients showed markedly less neurites per dopaminergic neuron and shorter neurites in both patient cohorts after 75 days of neuronal differentiation. The number of caspase3 positive cells, however, was also significantly increased in patient derived neurons pointing toward higher rates of cell death in these cultures. The neuritic phenotype appeared rather simultaneously to the degeneration of the dopaminergic neurons in this iPSC derived PD model. Using another approach to generate dopaminergic neurons from LRRK2 patient derived iPSC carrying the identical G2019S mutation, Borgs et al. detected a different phenotype. LRRK2 patient derived neurons that were generated from neural progenitor cells using small molecules showed a reduced total neurite length and increased neurite branching while the number of TH positive neurons was not altered after 35 days of differentiation.

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How Is It Treated And Is There A Cure

For now, Parkinsons disease is not curable, but there are multiple ways to manage its symptoms. The treatments can also vary from person to person, depending on their specific symptoms and how well certain treatments work. Medications are the primary way to treat this condition.

A secondary treatment option is a surgery to implant a device that will deliver a mild electrical current to part of your brain . There are also some experimental options, such as stem cell-based treatments, but their availability often varies, and many aren’t an option for people with Parkinsons disease.

Axonal Degeneration In Murine Pd Models

In order to get a more precise insight into the temporal pattern of degenerative events, several animal as well as cellular models are relevant:

Numerous transgenic animal models for PD have been generated, mostly carrying mutations in genes associated with monogenic PD such as alpha-synuclein, leucine rich repeat kinase 2 , Parkin, PTEN-induced putative kinase 1 , and protein deglycase DJ-1 . Longitudinal studies provide important information about the temporal progression of neurodegenerative events within the dopaminergic system .

FIGURE 1. Loss of dopaminergic terminals in the striatum precedes loss of substantia nigra pars compacta dopaminergic neurons in transgenic mouse models of PD. While the number of serotonergic neurons within the medium raphe nuclei was not changed in different transgenic mouse models of PD, the innervation of the hippocampal formation and the glomerular layer of the olfactory bulb was diminished together with depressive symptoms and impaired olfaction, respectively.

While there was already some evidence for the onset of PD pathology within projection areas of dopaminergic neurons, recent animal studies revealed a similar temporal pattern of events within the serotonergic system of murine PD models .

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Changes In Cognition And Parkinsons Disease

Some people with Parkinsons may experience changes in their cognitive function, including problems with memory, attention, and the ability to plan and accomplish tasks. Stress, depression, and some medications may also contribute to these changes in cognition.

Over time, as the disease progresses, some people may develop dementia and be diagnosed with Parkinsons dementia, a type of Lewy body dementia. People with Parkinsons dementia may have severe memory and thinking problems that affect daily living.

Talk with your doctor if you or a loved one is diagnosed with Parkinsons disease and is experiencing problems with thinking or memory.

Support For People Living With Parkinsons Disease

While the progression of Parkinsons is usually slow, eventually a persons daily routines may be affected. Activities such as working, taking care of a home, and participating in social activities with friends may become challenging. Experiencing these changes can be difficult, but support groups can help people cope. These groups can provide information, advice, and connections to resources for those living with Parkinsons disease, their families, and caregivers. The organizations listed below can help people find local support groups and other resources in their communities.

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Difficulty Reading Caused By Amd And Pd

People with AMD find that reading can become difficult. This is because their central vision that provides details and the sharpest visual acuity has been diminished.

Some people with Parkinsons disease also find that reading becomes difficult. This is because the disease affects eye movements that are important for reading:

• Convergence eye movements These are inward eye movements when looking at something close up, like a book or a tablet. PD decreases an individuals ability to converge their eyes when looking up close . And this results in double vision.

• Saccadic eye movements These rapid eye movements help a reader jump from one line of text to the next, and can become slow in PD.

• Pursuit eye movements These occur when your eyes follow a moving object. Decreasing pursuit ability makes it hard for someone to read scrolling text.

Parkinsons Disease: Symptoms Stages And Treatment

Parkinson’s disease usually begins after age 60, gradually progressing over the years. Some people can have early-onset Parkinson’s disease, starting in their 30s or 40s. It is primarily a movement disorder characterized by resting tremors and slowness and stiffness of movement.

In the late stages of the disease, Parkinson’s dementia can develop. But most people who have Parkinson’s disease do not develop dementia as a part of the condition.

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What Tests Will Be Done To Diagnose This Condition

When healthcare providers suspect Parkinsons disease or need to rule out other conditions, various imaging and diagnostic tests are possible. These include:

• Positron emission tomography scan.

New lab tests are possible

Researchers have found possible ways to test for possible indicators or Parkinsons disease. Both of these new tests involve the alpha-synuclein protein but test for it in new, unusual ways. While these tests cant tell you what conditions you have because of misfolded alpha-synuclein proteins, that information can still help your provider make a diagnosis.

The two tests use the following methods.

• Spinal tap. One of these tests looks for misfolded alpha-synuclein proteins in cerebrospinal fluid, which is the fluid that surrounds your brain and spinal cord. This test involves a spinal tap , where a healthcare provider inserts a needle into your spinal canal to collect some cerebrospinal fluid for testing.
• Skin biopsy. Another possible test involves a biopsy of surface nerve tissue. A biopsy includes collecting a small sample of your skin, including the nerves in the skin. The samples come from a spot on your back and two spots on your leg. Analyzing the samples can help determine if your alpha-synuclein has a certain kind of malfunction that could increase the risk of developing Parkinsons disease.

The Cerebellum And Parkinsonian Tremor

The classic type of tremor in Parkinsons disease is resting tremor. Parkinsonian resting tremor is mainly caused by central mechanisms because peripheral deafferentation does not suppress it . The pathophysiology of Parkinsons disease tremor certainly differs from that underlying akinesia/rigidity . Akinesia/rigidity is related to dopamine depletion and is typically responsive to dopamine treatment. The striatal dopamine depletion and dysfunction of basal ganglia seem to be more important in akinesia/rigidity than in tremor. Although still debatable , increasing evidence suggests that the cerebello-thalamo-cortical circuit is an important underlying pathophysiology of the parkinsonian resting tremor. For example, electrophysiological recordings in the thalamus of MPTP-treated monkeys showed that during tremor, the mean firing rate of neurons in the pallidal and cerebellar territories increases .

Tremor-related cerebral activity in tremor-dominant Parkinsons disease. Location of cerebral regions where activity cofluctuated with tremor amplitude. Activity was localized to the motor cortex, ventral intermediate nucleus of the thalamus and cerebellum . BA = Brodmann area lob = lobule VIM = ventral intermediate nucleus. Reprinted from, with permission from John Wiley and Sons.

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