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Monday, February 8, 2021

Parkinson’s disease

Parkinson’s disease is a movement disorder due to reduced secretion of dopamine, a chemical substance in the part of the brain which controls willing movements (basal ganglia). It was named after London physician James Parkinson who described its symptoms in 1817. 

There are no specific diagnostic methods to prove the existence of disease, so a detailed neurological exam is necessary.
To establish diagnosis it is important to determine general and neurological state of the patient, and if necessary do a levodopa test.

Main symptoms:

  • tremor (shivering) while resting; usually more pronounced in one side of the body
  • rigor (stiffness of arm, leg, and neck muscles)
  • bradykinesia (slow movements)

To estimate the degree of disease the results procured by Parkinson’s disease scale are used (Hoehn and Yahr Staging of PD; UPDRS), helping treat and estimate the disease.

UPDRS (Unified Parkinson Disease Rating Scale) is a scale of three question groups about mental state, behaviour, mood, ability to perform everyday activities, and motoric activity.  

Maximum score of 199 represents the worst kind of disability. Positive levodopa treatment reaction confirms the diagnosis.

Additional diagnostic procedures such as brain computer tomography (CT) or magnetic resonance (MR) can help rule out certain neurological or vascular disorders with similar symptoms, but cannot prove the existence of disease.
Parkinson’s disease clinical image
The disease develops slowly and few months, even years, can pass before the patient realizes the symptoms. 

Three main symptoms of Parkinson’s disease:

  • tremor (shivering)
  • rigor (stiffness of arm, leg, and neck muscles)
  • bradykinesia (slow movements)

Other than these three symptoms, postural instability also occurs (problems with balance). Symptoms do not need to occur simultaneously nor with same intensity. 

Tremor (shivering) is for the wide public the synonym for Parkinson’s even though only 25% of patients experience only weak tremors or even none at all. Its characteristics include rhythmical shivering and unwilling movements of certain body parts, as a consequence of repeated muscle contractions. It stops during sleep or rest, and as time passes the periods of tremor are longer. It begins asymmetrically in the arms, first one then the other (stereotype – counting the money), then legs, lower jaw, tongue, and head.

It is vital to know that tremor can have different causes and not all tremor patients have Parkinson’s.

Rigor (stiffness) is enhanced muscle tone or stiffness, usually present in neck, shoulders, pelvis, hands, and feet, resulting in typical position of Parkinson’s disease patient – half-bent thorax with legs bent in knees and arms bent in elbows. Stiffness is often responsible for mask-like facial expression. In some patients stiffness leads to pain, especially in arms and shoulders. It enhances during movement. 

Bradykinesia equals slow movement. This symptom nourishes functional damage. It is characterized by slow beginning of movement and reduced movement amplitude, caused by slow transfer of necessary information from the brain to certain body parts. When the body receives instructions, it reacts slowly to them. Normal associated movements (waving our arms while walking, blinking, gesticulation during conversation) are notably reduced. Everyday activities including fine movements are slow (buttoning up, tying your shoes, turning in bed).  
Postural instability (problems with balance) – occurs as a result of losing postural reflexes, autonomous reflex mechanisms which control the state of standing upright and protect the person from falling during change of position. Falling (loss of balance) is in Parkinson’s patients present in change of walking direction or sitting down into a chair

Other common traits are depression, dementia, dreaming, urination, and defecating disorders. Changes in handwriting are also present (micrographia – letter size diminishes during writing) and speech (slow speaking start, quiet, monotonous, hard to understand). Often seborrhea and over-sweating are also present.  

Speed of disease progression is different from patient to patient. In some patients even for prolonged time the disease does not affect everyday activities. It is important to discover the disease early and treat it properly.  

Treatment of Parkinson’s 
Treatment is symptomatic and does not stop progression of disease. Individual approach is very important, based on age and degree of disease, in order to help with the quality of life. 
Early diagnosis is important, as well as taking certain drugs, good nutrition, and exercise.
Treatment is very successful in early stage when symptoms can be controlled with a single drug. In advanced phases a combination of several drugs with different mechanisms is needed. For proper dosage, gradual titration in a longer time period is needed. 
Treatment of Parkinson’s disease disease non-pharmacological factors as well (exercise, nutrition, support groups). 
The goal of treatment is to achieve continuous stimulation of dopaminergic neurons via administering antiparkinsonics (drugs for treating Parkinson’s).    

Most common drugs used in Parkinson’s disease treatment:

  • levodopa (levodopa/carbidopa, levodopa/benserazide) – one of most efficient drugs; it is directly converted into dopamine, restoring lack of physiological dopamine which leads to PD. It is commonly prescribed along with enzyme decarboxylase inhibitors (carbidopa, benserazide) which stop its fast degradation and help larger dose of levodopa to be transferred to the brain. In the beginning of therapy, levodopa gives great results and provides good control over Parkinson’s disease symptoms, but as the disease progresses and levodopa is used for a long time, its efficiency weakens and motoric oscillations are experienced – levodopa dosage has weaker effect and dyskinesia appears (uncontrolled movements including twisting of hands, arms, feet, thorax, and head) which are most present when levodopa concentration in the brain is at its highest, and they also enhance with upping the dosage. So, according to therapeutical algorithm, levodopa is recommended in advanced PD therapy, by itself or combined with other drugs (COMT inhibitors, dopamine agonists, MAO inhibitors etc).
  • direct stimulators of dopaminergic neurons (apomorphine, bromocriptine, pramipexole, ropinirole) – directly stimulate dopamine receptors and replace the role of dopamine in the brain; in early stage of disease they are taken as monotherapy, and later in combination with levodopa.
  • apomorphine is the oldest dopamine agonist, taken via subcutaneous injections in situations of difficult „off“ episodes when the patient is completely stiff and reacts to no usual therapy
  • bromocriptine belongs to older generation of dopamine agonists, so called ergot group, which is not all that common these days
  • ropinirole, pramipexole belong to the new generation of non-ergot group, administered already in early stage of disease in small dosages which are slowly titrated. Their early usage postpones using levodopa, and later when levodopa is administered as well, it enhances its effect and levodopa’s dosages can be reduced.
  • enzyme monoaminoxydase type B inhibitors (MAO B inhibitors – selegiline) – blocks enzymatic path of dopamine decomposition thus enlarging the dopamine available. It is believed it can slow down PD progression if administered in early stage of disease, before levodopa is needed. However, clinical studies have yet to confirm its neuroprotectivity and ability to slow down PD. 
  • enzyme catechol-O-methyltransferase (COMT-inhibitors – entacapone) – blocks levodopa decomposition before entering the brain, taken only along levodopa, prolongs its effect. With entacapone, it reduces levodopa dosage for 20-30%.
  • anticholinergics (biperiden) – first drugs administered in PD therapy, in usage for more than 100 years, good for treating tremors but have many side-effects in long-term usage (dry mouth, blurred vision, constipation, urine retention, sedative effect, hallucinations, confusion)
  • amantadine – not available in Croatia, and usually administered in early stage of disease. Even though it was primarily used as antiviral drug in treating the flu, it was noticed it has beneficial effects in treating PD (the exact mechanism remains unknown). It eases the symptoms somewhat and is administered in early stages.    
Parkinson's disease

Surgery and/or implantation of stimulators are done only in patients who have developed uncontrollable movements that cannot be successfully treated with drugs. 

Appropriate house care and help are important for the patient in order to have a quality life. Encouragement is vital, as is participating in physical and work therapy and helping with reintegration into family activities. Family members can help a lot with patient’s feelings of depression, anger, and discomfort due to needing other people’s help

Physical therapy was found useful for patients with Parkinson’s. Due to stiffness muscle activation is reduced and they become more stiff and immobile. That is why it is vital to stay active through as many everyday activities as possible, including exercise. Even though exercising will not stop disease symptoms or slow down its progression, it will improve patient’s physical and mental state.

Patients with Parkinson’s disease need a balanced nutrition in order to have a satisfying amount of energy and drug effect. It is important to satisfy everyday nutrition and immunity needs.

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