Parkinson's Disease and Related Disorders
Parkinson’s disease (PD) is currently recognized as one of the most common neurological diseases. PD is a slowly progressing neurodegenerative disorder that afflicts around 1.5 million people in the U.S. alone, with 50,000 to 60,000 new cases diagnosed each year. Worldwide, it is estimated that approximately five million people have PD.
Global burden of Parkinson's disease, measured in disability-adjusted life years (per 100,000 inhabitants).
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The signs and symptoms of PD can be divided into two distinct categories, motor and non-motor, depending on whether they are related to body movement abnormalities or not.
Motor symptoms, which primarily affect the movements of the body, are the most obvious and well-known clinical features of PD. The chief motor symptoms are slowness of movement (bradykinesia), tremor, muscle stiffness (rigidity), and in later stages of the disease poor balance (postural instability).
Early in the course of the disease these symptoms are usually mild and confined to one side of the body. However, over the years as the disease progresses, the symptoms worsen, spread to another limb from the same side of the body and eventually to the other side, becoming increasingly impairing. While symptoms usually progress slowly, this can vary from one person to another.
Motor symptoms are usually preceded by non-motor symptoms that include: depression, loss of smell (anosmia), constipation, and vivid dreaming (REM-behavior disorder). However, these individual symptoms are very frequent in the general population, the most likely to precede the motor symptoms is the REM-behavior disorder. The UCSD Department of Neurosciences and movement disorder group are involved in studies searching for markers that could help diagnose PD at earlier stages.
It is now widely recognized that PD is a complex disorder with many non-motor manifestations (including neuropsychiatric) in addition to its better-known motor symptomatology. These non-motor symptoms affect the person's mood (e.g., depression), senses (e.g., smell, taste), and ability to think quickly. The most bothersome non-motor symptoms are: cognitive impairment and eventual dementia, depression, fatigue, drop of blood pressure when standing, and urgency to urinate. PD patients also complain of olfactory dysfunction, and pain in affected limbs.
Although the cause of PD remains unknown, remarkable advances have been made in understanding the possible underlying mechanisms. In normal circumstances, certain brain cells (neurons) are dedicated to the production of dopamine, a chemical important for the communication of neurons within the motor pathways and hence the control of movement.
In people with PD, these neurons, which are located in the area of the brainstem called Substantia Nigra, stop working properly and gradually degenerate and die (neurodegeneration). As a result, dopamine availability decreases and the symptoms progressively develop, becoming more severe over time.
Aggregation (clumps) of a protein that normally exists in the cells, called alpha-synuclein, is found in PD, forming round structures within the cell known as Lewy bodies. The factors and exact mechanisms that lead to the aggregation of alpha-synuclein and to the death of the dopaminergic neurons in PD are still not fully understood.
Most movement disorders specialists believe that PD results from a complex interplay between genetic predisposition and environmental factors. When the symptoms present at a younger age (below age 40), Parkinson’s disease is often familial (hereditary), caused primarily by genetic mutations of alpha-synuclein or its degradation system. As familial PD only accounts for a small percentage of cases, the majority of patients have the so-called “sporadic” (no other family members affected) form of the disease. In this case both genetic and environmental risk factors seem to play a decisive role, including genetic predisposition, accumulation of products of oxidative injury (free radicals), exposure to herbicides/pesticides, heavy metals (manganese) and toxins (MPTP) among others.
There are no blood tests or imaging exams that can establish the diagnosis of PD, although they may be helpful ruling out other possible causes of the symptoms. The diagnosis is clinical and is based on the person’s medical history and careful general physical and neurologic examination.
As a rule, two of the three primary motor symptoms (bradykinesia, tremor and rigidity) must be present to make the diagnosis, with one of the symptoms being bradykinesia. The presence of other associated features (e.g. symptoms began on one side of the body or are asymmetric; the tremor occurs at rest; the symptoms improve with PD medications; and suggestive non-motor manifestations) help supporting the diagnosis.
The signs and symptoms of PD can occur in people with other neurologic conditions, namely the so-called “Atypical parkinsonism” or “Parkinson-plus syndromes” (e.g. Progressive Supranuclear Palsy, Multiple System Atrophy, Corticobasal Degeneration, Dementia with Lewy Bodies). These patients experience symptoms that resemble PD (mainly in the early stages of the disease), but in addition have clinical features and a response to treatment that are not typically seen or expected in PD.
Moreover, certain medications (e.g. chlorpromazine; haloperidol; metoclopramide; reserpine; valproate) used in many clinical settings may also produce symptoms similar to PD (drug-induced parkinsonism), making the pharmacologic history a matter of utmost importance. It is important to distinguish PD from all these other conditions because treatment differs.
The symptoms of Parkinson’s disease can be managed effectively for a significant period of time. Although there is still no cure for PD, there are currently many medical and surgical treatments available for PD and other degenerative diseases of the central nervous system.
The treatment should be individualized, as numerous factors have to be taken into careful consideration, including the patient's symptoms/signs, age, stage of disease, degree of functional disability, and level of physical activity and productivity. Therefore, the options and decisions may vary significantly from one patient to another.
Considering the ongoing research and clinical trials, as well as the recent advances in the understanding of PD, it is realistic to expect some breakthroughs in PD treatment in coming years.
For a better understanding, treatment can be divided in pharmacologic (drugs), nonpharmacologic, and surgical therapy.
The pharmacologic treatment of PD can be divided into neuroprotective (to stop dopamine-producing nerve cells from dying, preventing the disease) and symptomatic therapy (to ameliorate the symptoms of the disease). In reality, nearly all of the available medications are symptomatic in nature and do not appear to reverse the natural course of the disease.
Different types of medications available to treat the symptoms of Parkinson disease include:
- Dopamine agonists
- Inhibitors of enzymes that inactivate dopamine: MAO-B (monoamine oxidase B) inhibitors and COMT (Catechol-O-methyltransferase) inhibitors
Levodopa molecule shown above.
It is important to note that adequate PD pharmacologic treatment is not limited to the above-mentioned medications (mostly aimed at controlling the motor symptoms), as non-motor manifestations (depression, dementia, psychosis, hallucinations, sleep problems) of PD often require directed drug treatment.
In addition to the pharmacologic management, PD is a chronic disorder that requires a broad-based approach. This includes several nonpharmacologic interventions that proved beneficial in the appropriate clinical setting, namely:
Education: the prospect of having a chronic and progressive neurologic condition is frightening. Education is essential to provide the patient and family with some understanding and control over the disorder. The given information must be comprehensible and adequate to the patient’s individual clinical situation, as early overexposure to some material may be counterproductive.
Support: the psychological and emotional needs of the patient with PD (and family) cannot be overlooked and should be addressed. Support groups are especially valuable, providing useful educational information and allowing interactions with other patients or families with similar experiences.
In some cases, referral to a psychologist experienced in dealing with chronic illness may be appropriate. Similarly, referral for legal, financial, or occupational counseling might be indicated.
Exercise and Physical Therapy: regular exercise promotes physical and mental welfare. Evidence suggests that regular aerobic exercise (e.g. brisk walks, tai chi, swimming, and water aerobic exercises) has a beneficial impact on PD, improving balance, flexibility and strength. In addition, many patients gain lasting confidence and sense of control over this aspect of the disease. Referral to a physical therapist or exercise group is advisable.
Speech Therapy: speech disturbances commonly afflict patients with PD. Evidence suggests that speech therapy for these patients may be helpful, especially improving speech volume and voice quality.
Nutrition: in more advanced stages of PD, the patients are at risk for poor nutrition, weight loss, and loss of bone and muscle mass. Prompt recognition and management may help prevent an unfavorable outcome. Some practical remarks can be made concerning the diet in PD: high fiber diet and adequate hydration help manage the constipation, and large high-fat meals that slow gastric emptying and interfere with medication absorption should be avoided.
Deep brain stimulation (DBS) is currently the mainstay surgical procedure for the treatment of advanced PD (and other movement disorders). This technique involves the surgical implantation of two leads into the brain (accurately targeting specific structures within the basal ganglia), which are then connected to a medical device similar to a cardiac pacemaker (neurostimulator) implanted just under the skin in the upper chest area.
The electrical impulses sent to these specific parts of the brain help improve the functioning of the motor pathways. DBS has several advantages in comparison to prior surgical interventions in PD: it does not involve destruction of brain tissue; is reversible; can be adjusted as the disease progresses or adverse events occur; and bilateral procedures can be performed without a significant increase in adverse events.
As not all patients are candidates for (or benefit from) surgical treatment, a careful patient assessment and selection by a movement disorders specialist is paramount.
Researchers at UC San Diego are currently looking at Parkinson's disease from multiple angles, from handwriting movements to cognition, to clinical trials to test FDA approved drugs.
Current research opportunities:
- Biomarkers for Parkinson's related cognitive problems
- Clinical trial for PD with cognitive impairment
- Clinical trial for PD with pain
- Cognition in PD and related disorders
- Handwriting movements
- Using MRI to study cognitive changes
- Using technology to study sensorimotor deficits in PD
Dr. Fatta Nahab is recruiting individuals with Parkinson's disease who are having memory or cognition problems for a 6 month long trial. This study will examine the safety and effectiveness of a new investigational medication, SYN120. It is hoped that SYN120 will help lessen or slow the cognitive decline of long-term Parkinson's patients. Eligible participants are over the age of 50 with a diagnosis of Parkinson's disease, are on a stable regimen of a cholinesterase inhibitor such as Exelon (RIVASTAGMINE), Aricept (DONEPEZIL), or Reminyl (GALANTAMINE) and have contact with a caregiver at least 3 times a week. Interested individuals should contact (858) 822 - MOVE or email firstname.lastname@example.org
for more information.
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