What is the prognosis of Parkinson’s disease?
Without treatment, the disease progresses to complete disability and can lead to death.
A well-chosen therapeutic approach affects the symptoms to a different degree and for a different length of time (depending on the form and progression of the disease).
What are the complications associated with long-term therapy of the disease?
- motor complications – motor fluctuations and dyskinesias. Motor fluctuations represent a disruption of the periods during which the patient has a good response to the applied therapy from periods during which the symptoms do not respond well. Initially, motor fluctuations occur in the morning and afternoon hours. There is a fluctuation in motor activity that is associated with taking each dose of levodopa due to exhaustion of the effect of the drug before taking the next dose.
As treatment continues, motor fluctuations become unpredictable, sudden. No relation to time to next dose or plasma levodopa concentration. Dyskinesias are involuntary movements that can be choreiform movements, dystonias, tics, myoclonus. They can affect any part of the body. They are more often observed in young patients. They occur during long-term therapy with levodopa or anticholinergic medications.
- neuropsychiatric complications – confusion, hallucinations, delirium, anxiety, panic attacks, depression, sleep disorders, cognitive disorders and dementia. Some of these problems are caused by the disease itself.
What is the treatment for Parkinson’s disease?
When treatment is started, symptoms respond well for varying lengths of time. This period is individual and depends on the form of the disease – tremor-rigid, rigid-bradykinetic. So also from the treatment being carried out.
Treatment can be substitutive or symptomatic by restoring dopamine levels or stimulating dopamine receptors. Preventive treatment aims to prevent the progression of the disease. In Bulgaria, a consensus has been adopted for the treatment of early Parkinson’s disease. According to him, the initiation of treatment with levodopa is delayed. In the early stages, MAO-B inhibitors (Selegeline) or Amantadine are used, which have a neuroprotective effect. These medications are usually effective during the first 3-4 years from the onset of the disease. When the clinical effect is exhausted, it is switched to taking levodopa preparations.
Levodopa is a precursor of dopamine and thus replenishes the dopamine deficit in the central nervous system. It is administered together with dopa-decarboxylase inhibitors, thus achieving reduced peripheral conversion of Levodopa to Dopamine. Dopamine agonists are drugs that directly affect striatal dopamine receptors. They are used in advanced Parkinson’s disease together with Levodopa. Such a preparation is the medication Pramipexol. Anticholinesterase medications (Akineton, Parkisan) are of limited use in therapy due to their significant side effects.
They are believed to primarily affect tremors. Modern therapy for Parkinson’s disease includes a drug with a neuroprotective effect to slow the progression of the disease and a drug with a controlled release of levodopa to ensure optimal levels of dopamine. When significant motor fluctuations occur, associated with taking each single dose of the drug, it is assumed that the patient is entering the stage of late Parkinson’s disease. At the same time, various complications are observed, caused both by the disease itself and by the medications taken.
The treatment of Parkinson’s disease is mainly based on replacement therapy of insufficient dopamine production by administration of levodopa (L-DOPA) or by simulating the dopamine effects by administration of dopa agonists such as pramipexole, ropinirole, pergolide or bromocriptine. Levodopa was discovered as a treatment option for Parkinson’s disease by Arvid Carlsson. Levodopa is a dopamine precursor that undergoes transformation into dopamine in brain structures. Preventive therapy aims to prevent the progression of the disease by applying preparations with a neuroprotective effect.
What is secondary parkinsonism (Parkinson syndrome)?
The term is used for a constellation of symptoms that is similar to that of Parkinson’s disease, but is caused by other disorders or by taking certain medications. Causes of parkinsonism can be vascular accidents, tumors, encephalitis, drug intake, medications (neuroleptics), intoxications (e.g. with manganese, carbon monoxide).
Vascular parkinsonism mainly affects lower limbs and gait disorder, simultaneous presence of rigidity and spasticity, ischemic foci on CT or MRI examination.
A differential diagnosis is also made with:
- essential tremor – postural tremor with familial presence. It responds well to beta-blockers and primidone.
- Huntington’s chorea – choreic hyperkinesias are observed.
- Alzheimer’s disease – early-onset dementia is characteristic.
- Creutzfeld -Jacob disease – early dementia, myoclonus, pyramidal symptoms
- Wilson’s disease (Hepatolenticular degeneration) – disturbances in copper metabolism, presence of liver damage, characteristic ring of Kaiser-Fleischer. Copper metabolism, ceruloplasmin levels, etc. are examined.
- disease with diffuse Lewy bodies – early and severe dementia, fluctuations in cognitive disorders, hallucinations, tremor is not a characteristic symptom.
What is the differential diagnosis?
A differential diagnosis should be made with other diseases in which parkinsonian syndrome is observed. Parkinson’s syndrome is characterized by the presence of static tremor, bradykinesia and/or hypokinesia, and muscle rigidity. This syndrome can enter the clinical picture of other neurodegenerative diseases, in which case it is accompanied by a variety of symptoms.
- multisystem atrophy – unites three different diseases – Shy-Dreger syndrome, striatonigral degeneration, olivopontocerebellar atrophy. It is characterized by the presence of parkinsonian, cerebellar and pyramidal syndromes and the presence of autonomic disorders. However, the symptoms are bilateral, there is no tremor, it is not affected by levodopa preparations. Progression is fast. Computed tomographic examination visualized atrophic changes in cerebellum, vermis and pons.
- progressive supranuclear paresis – combines parkinsonian, pseudobulbar and dementia syndromes and supranuclear vertical gaze paresis when looking down. There is a characteristic posture of the head in extension due to increased tone of the axial muscles more in the upper body.
Patients with these diseases often initially present with typical parkinsonian symptoms. That is why the exact diagnosis can be made after time when clinical signs specific to these conditions appear.
These diseases usually progress more quickly than Parkinson’s disease, and the usual antiparkinsonian medications are not effective in controlling the typical symptoms.
How is the diagnosis made?
In order to establish the diagnosis of Parkinson’s disease, the presence of at least two of the cardinal symptoms is necessary .
The unilateral manifestation of the symptoms at the beginning of the disease is characteristic . Most often, the presence of a resting tremor is initially detected. The severity of symptoms increases by about 8-9% per year. Patients are confined to bed due to disability after an average of 14 years. The progression of the disease is individual and faster during the first 4-8 years.
The form of the disease also matters for the progression of the disease. Progression is slow with disease onset before 50 years of age and with initial onset of tremor. It is faster with late onset of the disease and with predominance of rigid-bradykinetic syndrome and dementia. Neuroimaging methods (computed tomography and magnetic resonance imaging) are primarily used to rule out another neurodegenerative disease in which symptoms characteristic of Parkinson’s disease may be observed.
What is the clinical picture in Parkinson’s disease?
Parkinson’s disease develops slowly and gradually with atypical complaints such as shoulder pain, stiffness, clumsiness. Over time, the main symptoms of the disease also develop, as characteristic of Parkinson’s disease is the asymmetric onset. As the disease progresses, the patient becomes severely disabled.
Four cardinal symptoms are formed:
- static tremor (tremor at rest) – in over 70% of patients, this is the first clinical sign. It usually starts unilaterally distally, most commonly in the arm. The tremor has a frequency of 3-7Hz. It is characteristic that it is rhythmic, disappears during movement and during sleep. It is intensified by emotional stress. Over time, it can involve the entire arm, leg, contralateral limbs.
- rigidity – is expressed by an increase in the muscle tone of various muscle groups. When examining muscle tone, rigidity is manifested as a constant resistance to passive movement of the limbs. The resistance can appear smoothly, but often there is a step-like interruption – the so-called “cogwheel phenomenon”, which can increase during the passive movement of one limb against the background of active movement of the opposite one.
- bradykinesia – is expressed in a delay in voluntary movements, difficulty in starting and performing automated movements. The clinical presentation includes loss of spontaneous facial expression – hypomimia or “masked face”, reduced blink frequency, hypophonia when speaking, monotonous speech, micrographia, reduced to absent physiological hand synkinesis when walking, loss of normal gestures, difficulty in self-care. Hypokinesia presents with reduced amplitude of movements.
- postural instability – a result of loss of postural reflexes, rigidity, akinesia.
In patients, there is a change in posture with flexion of the head and body, with the arms retracted to the body, flexed at the elbow joints. Gait becomes slow, with small steps, with difficulty in starting, turning, stopping. Pulsation phenomena appear . When the patient is pushed, he staggers and begins to take quick small steps to maintain his balance. Depending on the direction, we denote this phenomenon as retro-, antero- or lateropulsio.
About half of patients develop a number of additional symptoms that are considered secondary. Such are cognitive disorders, dementia , in which it is necessary to make a differential diagnosis with Alzheimer’s disease and progressive supranuclear paresis. There are also disorders of the autonomic nervous system, which are expressed in the presence of orthostatic hypotension, constipation, urinary and sexual disorders. If these secondary symptoms are observed at the beginning of the disease, it is necessary to make a differential diagnosis with other neurodegenerative diseases, in which some of the cardinal symptoms of Parkinson’s disease also develop.
A bit of theory
When an impulse is generated by the brain to move (eg raise an arm), the impulse travels through the basal ganglia. The basal ganglia form the strio-pallido-nigral system. They participate in the formation of closed feedback loop systems. The purpose of these systems is to provide processed information to relevant cortical areas.
The basal ganglia are responsible for smoothing muscle movement and coordinating changes in posture. Neurons in the basal ganglia release neurotransmitters that trigger the next neurons along the nerve impulse’s path to carry out its transmission. The main neurotransmitter in the basal ganglia is dopamine.
In Parkinson’s disease , degeneration of the melanin-containing neurons in the pars compacta of the substantia nigra is found . Such changes are also found in the locus ceruleus, raphe nucleus, Meinert’s basal nucleus, hypothalamus, and temporal cortex. This leads to a decrease in dopamine levels and disruption of connections between neurons in the basal ganglia. Development of gliosis is established . Intracellular inclusions called Lewy bodies are seen at sites of cell loss. Lewy bodies can also be found in other neurodegenerative diseases, but their localization is different in different diseases.
As a result of the described changes, the basal ganglia cannot “smooth out” the motor act , which leads to the development of tremors, changes in coordination and to the slowing down and reduction of the motor act (bradykinesia).
The symptoms of Parkinson’s disease are the result of degeneration of nigrostriatal dopaminergic neurons with a decrease in the level of dopamine and subsequent mediator imbalance . One of the feedback systems in which the basal ganglia participate is the so-called motor circuit. Direct and indirect extrapyramidal pathways are formed in it. The direct pathway has an excitatory effect on cortical neurons, and the indirect pathway has an inhibitory effect. The balance between the activities of the two pathways ensures normal motor activity.
Dopamine has opposing effects on the direct and indirect extrapyramidal pathways. It activates the direct and suppresses the indirect pathway. When the level of dopamine in the substantia nigra decreases, the balance is disturbed in favor of the indirect pathway. Since the direct pathway facilitates the motor act and the indirect pathway suppresses the movements, the loss of the specified neurons leads to a hypokinetic movement disorder.
Symptoms usually occur when about 80% of the dopamine-secreting neurons in the substantia nigra are lost. Recent studies based on positron emission tomography (PET) report that symptoms can also be observed when 50-60% of dopaminergic neurons are lost. Dopamine levels continue to decline gradually over time. This is accompanied by further deterioration of the clinical picture.
What is the etiology of Parkinson’s disease?
The reason for the development of the disease is unspecified . Parkinson’s disease is currently believed to result from degeneration of the substantia nigra . The process is probably triggered by the impact of several factors:
- genetic factors – research in the field of genetics has established the existence of nine different specific genetic defects that are associated with the development of the disease in families with a particularly high incidence of the disease. About one-third of all Parkinson’s patients have a family history of the disease. A gene defect in the 4th chromosome was found in families with an autosomal dominant type of inheritance of the disease. A mutation was also found in the alpha-synuclein gene (chromosome 4q) and in the parkin gene (chromosome 6q), as well as in the ubiquitin hydrolase gene (chromosome 4p). In conclusion, there is compelling evidence for the importance of genetic factors in Parkinson’s disease.
- toxic factors – the toxic agent MPTP (1-methyl,4-phenyl,1,2,3,6 tetrahydropyridine) can cause destruction of cells in the substantia nigra. Over 100 other compounds have similar structure and activity and can cause the changes indicated.
- oxidative stress – the body contains natural antioxidants that protect cell structures from the harmful influence of free radicals that damage the cell membrane, various cell proteins and the functions of the mitochondria in the cell. For example, glutathione is a natural antioxidant. Its reduction is the earliest biochemical marker of nigral degeneration, even in the preclinical stage of the disease.
- mediator imbalance – presence of dopamine deficiency with a relative predominance of cholinergic activity. A decrease in naradrenergic, serotonergic and GABAergic mediation is also reported.
What is Parkinson’s disease?
Parkinson’s disease is one of the most common neurodegenerative diseases. It is a slowly progressive disease characterized by tremors at rest , slow voluntary movements ( bradykinesia ) and increased muscle tone ( rigidity ).
The disease was first diagnosed in 1817, when the Englishman Dr. James Parkinson described the characteristic clinical symptoms. Disease-related biochemical changes in the brains of patients were identified in the 1960s.
It covers about 80% of cases of Parkinson’s syndrome, with the average age at which the first complaints appear being about 55 years for both sexes. The incidence of Parkinson’s disease is estimated to be approximately 160/100,000 and the incidence 20/100,000 per year. Caucasians have a higher risk of developing this disease. The risk of developing the disease increases with age.
The disease occurs in all parts of the world, but is more common among Europeans (the white race) than among the population of Africa. East Asians have an average risk. It is more common in the rural population and slightly more common in men than in women.
