Parkinson’s Disease

Written By: Aleksej Savelev

Aleksej Savelev

PhD in Medicine

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Causes and Possible Risk Factors

Parkinson’s Disease – multifactorial disease. Most often it occurs as a result of a combination of genetic and environmental factors

• Genetic factors Genetic polymorphisms are identified in 10-15% of all cases of Parkinson’s disease, especially with onset before the age of 50, in familial cases.
• External factors . Age and gender are significant non-modifiable risk factors for the development of PD: it is noted that the disease more often affects men over 60 years old. Modifiable risk factors include lifestyle, nature of professional activity, medication intake, tobacco use, past injuries, exposure to metals, pesticides, etc. Currently, their direct relationship with the development of Parkinson’s disease continues to be studied. It is assumed that depressive states, brain injuries, and decreased vitamin levels D, migraine with aura in adulthood, living in urban or industrial areas with high emissions of copper, manganese, or lead, exposure to hydrocarbon solvents (especially trichloroethylene), excess body weight, high consumption of dairy products, and pesticide exposure are presumably associated with an increased risk of developing PD. As etiological factors that reduce the risk of the disease, the following are suggested: long-term smoking, caffeine consumption, statins, non-steroidal anti-inflammatory drugs, and high levels of uric acid in the blood. There is evidence that the presence of melanoma or prostate cancer is associated with an increased risk of developing PD. **

Buzaev Clinic – here you can eliminate tremor in Parkinson’s disease

Early signs

1. Tremor
2. Change in handwriting with a tendency to decrease the size of letters
3. Reduced sense of smell
4. Sleep problems
5. Movement disorders
6. Constipation
7. Voice changes
8. Changes in Emotional Expression
9. Dizziness, Fainting
10. Postural slouching

Symptoms

Motor symptoms:

• Resting tremor – the classic “parkinsonian” shaking that occurs in a relaxed position (or while walking) and resembles “pill rolling” or “coin counting”
• Б radikinesia (slowness)
• G Hypokinesia (reduction of movement amplitude)
• О Ligokinesia (slowing of movements)
• Muscle rigidity, manifested by increased muscle tone and a feeling of stiffness
• Facial expression impoverishment (“mask-like face”)
• Voice changes (becomes quieter), speech (dysarthria), swallowing (dysphagia)
• Change in handwriting (small, bead-like handwriting)
• Vision problems: blurred vision, decreased contrast sensitivity, hypometric saccades, impaired vestibulo-ocular reflex, convergence insufficiency, eyelid opening apraxia, reduced frequency of spontaneous eye blinking
• Camptocormia (severe forward flexion of the thoracolumbar spine), difficulty turning in bed, reduced arm movement activity while walking
• Postural instability – usually appears in the later stages of the disease.

Depending on their ratio, currently, there are 3 forms of Parkinson’s disease: tremor-dominant, akinetic-rigid, and mixed.

Non-motor symptoms:

In Parkinson’s disease, in addition to movement disorders, a wide range of non-motor changes (not related to movements) is noted

• Mood change
• Depression
• Psychotic disorders (cognitive deficit, dementia, psychoses, and hallucinatory-delusional disorders)
• Sleep disorders
• Fatigue and lack of energy
• Urological issues (urination disorders, nocturia, frequent urges, urinary incontinence)
• Problems in the Sexual Sphere
• Olfactory and Taste Disorders
• Gastrointestinal issues (nausea, vomiting, constipation, increased urge to defecate);
• Unexplained Pain Syndrome
• Skin problems (seborrhea)
• Drooling
• Weight loss

Stages

In 1967, it was proposed to describe the stages of PD according to the Hoehn and Yahr scale:

Stage 1: symptoms manifest to a degree that does not hinder the performance of daily activities. Movement disorders affect one side of the body. Early signs of the disease may be observed without significant changes in the motor sphere (stooped posture, changes in gait, and changes in facial expressions)

Stage 2: Motor symptoms occur on both sides or along the midline of the body (e.g., in the neck and torso). Postural instability is not characteristic of this stage. The person is capable of self-care with difficulties.

Stage 3: progression of movement disorders leads to postural instability and frequent falls. There is a more pronounced limitation of daily activities and a change in quality of life, however, the ability for self-care is preserved

Stage 4: a person can still walk and stand without assistance, but the risk of falls is extremely high. The person is unable to care for themselves and requires significant help in daily life.

Stage 5: severe muscle rigidity completely restricts walking. The person is bedridden or moves in a wheelchair. Round-the-clock care is required as the ability for self-care is completely lost. *

Diagnostics

The diagnosis of “PD” is made clinically, based on medical history and neurological examination.

According to the criteria of the International Movement Disorder Society MDS) *** the presence of the following movement disorders is mandatory :

• Bradykinesia
• 1 types of tremor
• Rigidity

Diagnosis of clinically established PD requires:

1. Absence of absolute exclusion criteria

2. The presence of at least two confirming criteria

3. Absence of “red flags”

Diagnosis of clinically probable PD requires:

1. Absence of absolute exclusion criteria

2. Presence of “red flags” balanced by the number of confirming criteria

Confirmation Criteria :

1. Clear and pronounced positive response to dopaminergic therapy

2. Presence of levodopa-induced dyskinesia

3. Limb tremor at rest, recorded during clinical examination (in the past or during the current examination)

4. Presence of loss of smell or cardiac sympathetic denervation on metaiodobenzylguanidine scintigraphy

Other clinical signs confirming the diagnosis are:

• Unilateral onset of the disease
• Persistent asymmetry throughout the illness;
• Postural instability is also a characteristic feature of PD, but it usually does not appear until a later stage of the disease. In patients with signs of parkinsonism who exhibit postural instability at the onset of the disease, another cause of the parkinsonism syndrome should be sought.

Absolute Exclusion Criteria:

1. Signs of Cerebellar Pathology (Cerebellar Ataxia, Cerebellar Nystagmus, Hypermetric Saccades)

2. Vertical supranuclear gaze palsy downward or selective slowing of downward vertical saccades

3. Frontal and temporal dementias, primary progressive aphasia, established within the first 5 years of the disease.

4. Symptoms of parkinsonism affecting only the lower limbs for more than 3 years.

5. Prolonged use of dopamine receptor blockers or other drugs that deplete dopamine reserves, in a dose and duration corresponding to drug-induced parkinsonism

6. Lack of noticeable response to high >1000 mg per day) doses of levodopa, despite the moderate severity of the disease.

7. Loss of cortical functions, ideomotor limb apraxia, progressive aphasia

8. Normal functional neuroimaging of the presynaptic dopaminergic system

9. Another confirmed disease that can mimic the symptoms of parkinsonism

«”Red Flags”

1. Rapidly progressing gait disturbance requiring regular use of a wheelchair within 5 years from the onset of the disease

2. Complete absence of progression of motor symptoms or signs for 5 or more years, with stability not related to prior therapy

3. Early bulbar dysfunction: severe dysphonia, dysarthria, or dysphagia within the first 5 years.

4. Inspiratory respiratory dysfunction: daytime or nighttime inspiratory stridor.

5. Severe autonomic insufficiency during the first 5 years of the disease

6. Repeating >1/year) falls due to balance disorders for 3 years from the onset of the disease

7. Disproportionate dystonia or contractures of the arms or legs within the first 10 years

8. Absence of non-motor symptoms of the disease despite its duration > 5 лет.

9. Unexplained signs of pyramidal tract lesions, identified as pyramidal insufficiency

10. Bilateral symmetrical parkinsonism

Laboratory Diagnostics

There is no specific laboratory diagnosis for PD.

Instrumental Research Methods

Are of low informational value, but can be used for differential diagnosis with diseases such as stroke or hydrocephalus.

• CT.
• MRI
• DaT scan. Reliable differentiation of Parkinson’s disease from other parkinsonism syndromes is enabled by imaging of striatal dopamine transporters using single-photon emission computed tomography.
• Sonography (Ultrasound). Hyperechogenicity of the substantia nigra is a prognostic factor for the clinical diagnosis of PD and is detected in 90% of PD cases.
• Olfactory tests. Rarely used in clinical practice as a diagnostic test for PD, but they allow differentiation of the disease from other parkinsonism syndromes.
• Autonomic tests – cardiac sympathetic denervation, confirmed by myocardial scintigraphy with metaiodobenzylguanidine, is relatively sensitive and specific for distinguishing PD from other neurodegenerative causes of parkinsonism.

Treatment

Medication therapy.

Main medications for treating motor symptoms of PD include:

• Dopamine precursors (levodopa)
• Inhibitors of dopamine activation enzymes (monoamine oxidase B inhibitors – selegiline, catechol-O-methyltransferase – entacapone, DOPA decarboxylase – carbidopa, benserazide)
• Agonists D2-receptors (bromocriptine, ropinirole)
• Anticholinergic agents (trihexyphenidyl, biperiden)
• Antagonists NMDA-receptors (Amantadine, Midantan)

Dopamine agonists can be used both as monotherapy in the early stages of Parkinson’s disease and in combination with other antiparkinsonian drugs for the treatment of more advanced forms of the disease.

Low doses of estrogen may be beneficial as an adjunct therapy in postmenopausal women with motor symptoms while taking antiparkinsonian medications.

Surgical intervention

DBS – Deep brain stimulation. Until recently, it was considered the most advanced method for combating the symptoms of Parkinson’s disease. However, the need to place an electrode in the brain, the difficulty of hitting the right spot, and the implantation of a stimulator with replaceable power elements created certain challenges and could cause various complications.
Image: www.mayoclinic.org

Deep Brain Stimulation
(Deep brain stimulation, DBS)

For patients with Parkinson’s disease who do not respond to levodopa therapy and develop movement disorders requiring high doses of the drug, which reduce quality of life, it is recommended to consider the implantation of a deep brain stimulation device. Disadvantages include: invasiveness of treatment, high risk of complications (infection, hemorrhage)

Surgical Methods Using Focused Ultrasound (FUS)

MRgFUS – non-invasive elimination of Parkinson’s disease symptoms with MRI-guided focused ultrasound. The most modern, effective, precise, and safe method, requiring no incisions, anesthesia, or implantation of devices into the human body.

Thalamotomy , thalamus stimulation

Indications for thalamotomy: tremor-dominant form of PD

Pallidotomy , stimulation of the globus pallidus and subthalamic nucleus

Indications for pallidotomy: akinetic-rigid form of Parkinson’s disease

Method Advantages: non-invasiveness, no need for anesthesia, no need for device implantation, the possibility of intraoperative monitoring via MRI

Video examples of non-invasive treatment of Parkinson’s disease with MRI-guided focused ultrasound at the V.S. Buzaev Clinic

Rehabilitation

Rehabilitation is an important part of treating Parkinson’s disease, as it can slow the progression of the clinical symptoms of the disease.   The V.S. Buzaev International Medical Centre has created the Community for Patients with Parkinson’s Disease “Semitsvetik”. Its goal is the motor and social rehabilitation of patients who have encountered this disease.

Forecast ****

Parkinson’s disease is not a condition that directly leads to death. However, PD belongs to a group of neurodegenerative disorders of the nervous system that often progress and lead to patient disability. The average life expectancy of people with Parkinson’s disease is the same or nearly the same as those without PD, but it can vary depending on health, diet, physical activity, presence of harmful habits, and other factors.

The most common causes of death among patients with PD:

• Falls . Patients with Parkinson’s disease are at increased risk of falls due to postural instability and other symptoms of Parkinson’s disease.
• Aspiration pneumonia – a common cause of death in people with Parkinson’s disease. Aspiration pneumonia occurs when swallowing difficulties (dysphagia) cause food to enter the airways and lead to infection. An excellent way to manage this risk for people with Parkinson’s disease is to perform exercises to strengthen the vocal cords and chewing muscles. If you are looking for a rehabilitation program, contact the V.S. Buzaev International Medical Centre (see the “Rehabilitation” section)

Sources:

*Parkinson’s Foundation, UpToDate

** UpToDate, «Clinical manifestations of Parkinson disease»

*** Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30(12):1591-1601.

**** https://parkinsonfoundation.org/blog/is-parkinsons-fatal-can-you-die-from-parkinsons-disease

What to do if you or your relative has Parkinson’s disease?

1. Undergo an online consultation with our neurologist specializing in Parkinson’s disease
2. The doctor will determine which treatment method is suitable for your specific case and prescribe it (surgery is not indicated in all cases and not at all stages of the disease)
3. We will monitor your condition (or the condition of your relative) and make adjustments to the treatment plan as needed.

Remember, Parkinson’s disease is not a sentence! The quality of life and prognosis for this condition can and should be improved, and we are ready to help you!

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