Parkinson’s disease: causes, symptoms, treatments and rehabilitation.

A hereditary disease can be passed down from parents to children through their genes. A genetic disease may be inherited or caused by random mutations.

Is Parkinson’s disease hereditary? Is there a genetic test for Parkinson’s?

Studies have shown that there are some cases of Parkinson’s caused by genetic mutations, but that hereditary causes of this disease are rare: only 15% of Parkinson’s patients have had other cases in their families.

Apart from these, the etiology of Parkinson’s disease is generally unknown.

Research suggests that the cause is a combination of genetic and environmental factors.

Key points:

• Parkinson’s very rarely runs in families.
• Most people suffer from “idiopathic Parkinson’s” (the cause is unknown).
• For a small minority of people with Parkinson’s, there is a genetic link.

 

Parkinson’s is a neurodegenerative disease that affects the nervous system, causing tremors (leg tremors, muscular tremors, etc.), slowness of movement, difficulties with balance, and muscle rigidity. It usually affects older people, but cases of Young Onset Parkinson’s Disease are increasingly frequent.

 

When does it appear?

Today, one in 10 Parkinson’s patients is under age 40 and one in four is younger than 50. This phenomenon is probably also linked to greater accuracy in Parkinson’s diagnosis, as it is now often identified at very early stages.

Clinical and epidemiological studies have shown that the earliest damage to the brain occurs an average of at least six years before the initial diagnosis.

Parkinson’s is no longer a disease affecting only the elderly. Juvenile Parkinson’s is an increasingly important topic. Younger patients find themselves facing premature aging as a result of physical degeneration, side effects of Parkinson’s drugs, and of a progressive lack of engagement in social relationships and activities.

 

Parkinson’s, AMPS and quality of life.

Although Parkinson’s disease does not significantly reduce life expectancy, it does have an impact on quality of life. With this in mind, AMPS treatment allows patients to improve their quality of living.

Parkinson’s is characterized principally by two main stages: presymptomatic and symptomatic.

The presymptomatic stage is usually characterized by the loss of dopaminergic neurons from the substantia nigra. It is not clear when this stage begins nor what percentage of dopaminergic neurons are lost.

It is also difficult to determine precisely when the symptomatic stage begins and identify the early symptoms of Parkinson’s disease (some are so mild that no clinical evaluation is possible).

The symptomatic stage can, in turn, be divided into two parts: early stage and late stage. The early stage is characterized by the onset of the motor symptoms of Parkinson’s and usually by the loss of about 70% of the dopaminergic neurons of the substantia nigra. The late stage consists of the disease progression, when symptoms becoming more severe, often causing significant disruption in daily activities.

The progression of the disease is unique in each case, with primary motor symptoms varying from patient to patient.

 

Parkinson’s disease symptom statistics:

• 70% of cases involve resting tremor, especially in patients suffering from Juvenile Parkinson’s.
• 89-99% of patients are affected by rigidity, 77-98% by bradykinesia, and 37% by balance impairments.
• 72-75% of patients exhibit disease onset on one side only.

There are therefore different forms of Parkinson’s. Some exhibit all of the cardinal signs, while some exhibit only tremor and others only akinesia or rigidity.

In cases where a person with Parkinson’s receives no treatment whatsoever, the progression of the disease is continuous, which is the reason for its classification into five stages by Hoehn and Yahr, as described below.

 

Stage 1

The early symptoms of Parkinson’s appear; these are often mild and affect only one side of the body.

In most cases, there is an onset of resting tremor in the upper limbs and a decrease in their functional capacity. Onset of akinesia, slight rigidity, difficulty in performing rapid alternating movements and impaired finger dexterity is often observed. There is a slowing down of walking? and of repetitive movements.

Handwriting becomes shaky, with curving lines becoming more of a challenge. There may also be a reduction in facial expression and, in some cases, seborrheic dermatitis of the forehead.

 

Stage 2

Symptoms begin to appear on both sides of the body. Posture becomes rigid and the trunk and limbs are slightly bent.

Onset of bradykinesia, which is the gradual slowing of all movements. Patients often exhibit reactive depression.

 

Stage 3

Symptoms translate into severe difficulty walking, which disables the patient; patients begin to exhibit retropulsion or propulsion.

There is a further deterioration in postural reflexes and patients develop the typical parkinsonian walk, with a festinating gait and the upper body leaning forward. Gait and bradykinesia worsen, while retropulsion and propulsion increase the risk of falling.

In this stage, patients may need help to perform certain actions.

 

Stage 4

High degree of disability. Patients require constant assistance, as they are no longer able to perform everyday activities or live alone.

Falls are very frequent and it is often difficult or impossible to control movement.

 

Stage 5

Complete incapacitation. Patient can no longer walk nor stand erect. When lying down, the patient remains supine and immobile, with the head bent slightly towards the trunk.

The mouth is constantly open due to dysphagia and issues of spontaneous swallowing. Dehydration and cachexia are also common problems due to difficulties in eating.

There is a high risk of infection due to reduced diaphragmatic excursion, impairment in cough reflex, neurogenic bladder and the fact of being bedridden.

THIS CLINICAL PICTURE REFERS TO A PERSON WITH PARKINSON’S WHO IS NOT UNDERGOING ANY PHARMACOLOGICAL TREATMENT.

The term parkinsonisms refers to a group of neurological conditions that cause movement impairments similar to those caused by Parkinson’s, such as tremors, slowness of movement and rigidity.

At the beginning of the disease progression, it can often be difficult to distinguish between idiopathic Parkinson’s (of unknown origin) and parkinsonisms.

Parkinsonisms, also known as atypical Parkinson’s or Parkinson’s Plus, account for approximately 10-15% of cases diagnosed as Parkinson’s. These syndromes tend to progress more rapidly than Parkinson’s disease and present with additional symptoms, such as early falling, dementia or hallucinations, and do not respond or respond only for a short time to treatment with the dopaminergic drug levodopa.

Parkinsonisms are called “atypical” syndromes because they usually differ from Parkinson’s disease in a number of ways:

• there is generally no tremor
• both sides (left and right) are usually affected in the same manner
• response to levodopa (L-Dopa) and other Parkinson’s drugs is poor
• deep brain stimulation (DBS) has no effect.

In early stages, parkinsonisms are treated in the same way as Parkinson’s, because no other specific treatments exist. Although they sometimes do respond to Parkinson’s medications, the response is never as good as when treating PD.

Other symptoms of parkinsonism are: eye movement abnormalities, an “ataxic” gait (wide based walking), dystonia (abnormal posture), severe problems related to low blood pressure when standing or changes on the neurological exam that are only detected by the neurologist in the form of abnormal reflexes.

This notwithstanding, the problems caused by parkinsonisms are the same as those caused by Parkinson’s disease: slowness, difficulty with movements, balance impairments, speech problems and falls. For this reason, it is often difficult to attribute the correct name to a condition. At the same time, these conditions occasionally lack certain key symptoms crucial for a correct clinical diagnosis.

Many people do not exhibit any of the cardinal signs required to diagnose a specific condition and so their symptoms are labeled as “parkinsonisms.”

 

Progressive Supranuclear Palsy (PSP)

PSP, also known as Steele-Richardson-Olszewski syndrome, is slightly more common than ALS. Onset of symptoms usually occurs around 60 years of age. The most common early symptoms include loss of balance when walking, episodes of memory loss and personality changes.

Vision problems associated with PSP generally appear after the walking problems and involve the inability to properly aim the eyes at a specific point.

Individuals with PSP may respond to dopaminergic treatment, although they may require higher doses than those with Parkinson’s.

 

Multiple System Atrophy (MSA)

MSA (also known as Shy-Drager syndrome) refers to a group of disorders in which one or more parts of the body ceases to function. The autonomic nervous system is often severely affected during the early stages of the disease.

Symptoms include bladder problems, with frequent and urgent need to urinate, difficulty urinating or, on the other hand, urinary incontinence, as well as orthostatic hypotension.

In men, the earliest sign may be erectile dysfunction. Other symptoms include impaired speech, difficulties in breathing or swallowing and an inability to sweat.

As with Parkinson’s, the early stages of MSA may cause rigidity and slowness of movement.

As in other parkinsonisms, the symptoms of MSA do not respond well or at all to Parkinson’s drugs.

 

Vascular parkinsonism

Vascular parkinsonism (also known as arteriosclerotic parkinsonism) affects people with limited blood flow to the brain.

Individuals affected by this condition tend to have more issues with walking than with tremor, and experience more problems in the lower part of the body.

This type of parkinsonism progresses much more slowly than others.

Onset of symptoms may be sudden or gradual. The most common symptoms include memory impairments, problems sleeping, and mood and movement disorders.

 

This type of parkinsonism usually responds poorly to pharmacological treatment, but some patients have experienced positive results with the GONDOLA treatment.

 

Dementia with Lewy Bodies (DLB)

DLB is the second-most common cause of dementia among the elderly after Alzheimer’s disease. It causes progressive intellectual and functional deterioration.

In addition to Parkinson’s disease symptoms, people with DLB tend to have frequent changes in thinking ability and level of attention and often experience visual hallucinations.

They usually have no or slight tremor.

The parkinsonian symptoms associated with DLB may or may not respond to levodopa.

 

Corticobasal Degeneration (CBD)

CBD is the least common type of atypical parkinsonism. It usually develops after 60 years of age. Symptoms include loss of function on one side of the body, involuntary and jerky movements of a limb and speech problems.

At this time, there is no specific treatment for CBD.

 

Normal pressure hydrocephalus (NPH)

Normal pressure hydrocephalus affects mainly the lower half of the body.

Its common symptoms are difficulty in walking, urinary incontinence and loss of memory.

In the short term, extracting some cerebrospinal fluid using a needle inserted into the lower part of the back may be of help. If there is an improvement following this procedure, an operation to deviate cerebrospinal fluid could help in the long term.

A doctor diagnoses Parkinson’s based on an examination of the patient’s medical history and, if deemed necessary, movement tests.

Due to the largely clinical nature of the diagnosis, Parkinson’s may be mistaken for a parkinsonism, and the diagnosis may need to be revised over time based on the speed of disease progression, response to medications and other factors.

All parkinsonisms involve a loss of dopamine, meaning that a DatScan cannot be used to differentiate between Parkinson’s disease and atypical Parkinson’s.

 

How are parkinsonisms diagnosed?

An appointment with a neurologist specialized in Parkinson’s is required for the diagnosis of any type of parkinsonism.

Distinguishing between the different types of parkinsonisms is not always easy because:

• the early symptoms of the different forms of parkinsonism are very similar, and
• the symptoms that allow a doctor to make a specific diagnosis may appear only as the condition progresses.

All of the parkinsonisms are different and have different symptoms, but there are many overlapping features (?).

 

Treating Parkinson’s and parkinsonisms

Parkinson’s treatments, such as dopaminergic drug therapy (the first line treatment for Parkinson’s), may be effective for certain aspects of parkinsonisms.

Regular exercise and rehabilitation are crucial for maintaining muscle tone, strength and flexibility.

Other common treatments for both Parkinson’s and parkinsonisms include physical, speech and occupational therapy, antidepressants, and botulin toxin (Botox) for dystonia. Health care providers aim to treat those symptoms that have the greatest impact on quality of life.

 

Response to Parkinson’s drugs

One of the most useful tests when it comes to identifying a specific type of parkinsonism consists of discovering how the patient responds to drug treatment.

If the doctor believes that the patient has idiopathic Parkinson’s, they will expect a positive response to dopaminergic drugs such as levodopa (co-careldopa or co-beneldopa), meaning an improvement in symptoms.

Occasionally, a patient’s response to a medication becomes clear only when the drug is reduced or stopped and the symptoms return, even stronger and more evident than before.

If symptoms are unusual and there is no response to Parkinson’s drugs, this does not automatically mean that the patient has another form of parkinsonism; however, the neurologist will probably want to revise their diagnosis.

In cases such as these, the doctor may use terms such as “atypical parkinsonism” or “Parkinson’s Plus.” This is not a diagnosis; however, it likely indicates a more complex situation than typical Parkinson’s.

The disease is characterized by three classic symptoms: tremor, rigidity and slowness of movement (bradykinesia). These symptoms may be associated with balance impairments, kyphosis (stooped posture), clumsy gait, sudden stops (freezing of gait, Parkinson’s freezing) and, in the late stages, akinesia (total absence of movement).

Minor early symptoms include: decrease in sense of smell, changes in handwriting (becoming progressively smaller), changes to the voice (becoming weaker and monotone), a fixed stare and a loss of facial expression.

 

Tremor in Parkinson’s

Tremor is a hyperkinetic movement disorder, characterized by the rhythmic oscillation of one or more body parts. It can be incapacitating and have a negative impact on quality of life.

Two of the types of tremor are essential tremor and Parkinson’s tremor (described below).

Although tremor is one of the classic symptoms of the disease, it is not the most significant; in fact, it does not affect 30% of patients.

Most studies focus on essential tremor; few are devoted to other types.

 

Essential tremor

Essential tremor (occasionally called benign tremor) is the most common type and is often mistaken for Parkinson’s tremor.

In some individuals this tremormay remain mild and unvarying for a long time, while in others it may start on one side of the body but gradually, over the course of just a few years, progress to affect both sides.

The hands are the most affected part, but this tremor may, usually to a lesser extent, affect the head, voice, tongue, legs and trunk.

 

Parkinson’s tremor

Parkinson’s tremor is caused by damage to the areas of the brain that control movement. The tremor usually occurs when at rest, for instance when the hands are resting in the lap, and disappears when the individual is actively moving.

It may occur as an isolated symptom or in combination with other symptoms. It is often the earliest symptom of Parkinson’s disease (over 25% of patients with Parkinson’s disease experience action tremors).

 

Dystonic tremor

Dystonic tremor occurs in individuals of any age who suffer from dystonia, a movement disorder in which the muscles contract involuntarily.

It can affect any muscle in the body and occurs more often when the patient is in a specific position or moves in a specific way.

It does not occur on a regular basis and can often be alleviated by absolute rest. Tremor can be the earliest sign of focal dystonia.

A dystonic tremor in the limbs may respond to anticholinergics, while botulin toxin improves head and voice tremor.

 

Orthostatic tremor

Orthostatic tremor is characterized by rhythmic muscle contractions in the legs or trunk and is usually perceived as unsteadiness. There are no other signs or clinical symptoms, and the unsteadiness disappears when the individual is no longer touching the ground or begins to walk.

Pharmaceutical therapies such as gabapentin and clonazepam are often recommended to treat this type of tremor.

 

Bradykinesia

Like tremor, bradykinesia, or slowness of movement, is one of the most significant symptoms of PD.

Patients often  describe having muscle weakness and difficulty in performing everyday movements coupled with feelings of clumsiness, lack of confidence and becoming easily fatigued. They also report experiencing greater difficulty in moving at their usual speed, as though their arms or legs were “tied” and rigid.

 

This symptom is treated with drugs, and there have also been excellent results achieved with the GONDOLA treatment (used in conjunction with medication).

 

Parkinson’s freezing and gait disorders

Posture tends to become stooped, there is a decrease in pendular arm movements and a reduction in stride length. Patients often present with “festination,” a shortening and quickening of stride until they are no longer able to move their feet.

Sudden motor blocks, known as freezing of gait or Parkinson’s freezing, may occur beginning in the middle stages of the disease.

In many cases, freezing is a side effect induced by the chronic use of dopamine agonists, one of the principal types of drugs used for the treatment of Parkinson’s disease.

Festinant and freezing gait can cause falls and, in some cases, render the patient unable to perform normal daily activities.

 

Balance impairments and pain

Suffering from Parkinson’s also means experiencing rigidity and muscle pain (46% of patients), movement disorders, loss of balance and unsteadiness.

Balance impairments appear during the middle to late stages of Parkinson’s disease. As the disease evolves, patients begin to lose their sense of balance and progressively lose the ability to automatically correct their posture.

 

Other signs

Hyposmia (a reduced sense of smell that also makes food taste flavorless) and orthostatic hypotension (a sudden drop in blood pressure when going from sitting to standing) can be early signs of Parkinson’s.

70% of Parkinson’s patients are affected by hyposmia, sometimes years before the onset of the disease; it is a symptom that can be viewed as an early warning sign.

Constipation, if resistant to any sort of treatment and without an apparent cause, may also be considered an early symptom of Parkinson’s.

In all of these cases, an appointment with a specialized neurologist can help to clarify the situation.

 

Juvenile Parkinson’s

25% of individuals with Parkinson’s are not aware of their condition, primarily because their symptoms are minimal and can be mistaken for those of other illnesses. This often results in a lack of correct diagnosis, especially in patients between 40 and 50 years of age.

For example, stiffness in a limb may be attributed to joint inflammation, rheumatism or poor posture, while instead it could be one of the early symptoms of Parkinson’s.

It is important to consider the appearance of early Parkinson’s symptoms as a possibility, regardless of an individual’s age, especially when clinical and diagnostic testing do not provide answers or confirm other conditions.

Who to see and when? From the earliest stages of the disease, every patient should place themselves in the care of a neurologist specialized in movement disorders.

There is no cure for Parkinson’s disease, but there are a number of different treatments to help manage the symptoms.Having the right treatments from the moment Parkinson’s symptoms first appear makes it possible to slow the progression of the disease and have a better quality of life than if treatment is begun later on.

Treatment of Parkinson’s disease focuses heavily on pharmacological treatments, but a number of different surgical approaches have been developed in recent years, as well as rehabilitation-based therapies such as AMPS (Automated Mechanical Peripheral Stimulation), which is provided by the GONDOLA^® medical device for Parkinson’s.

Drugs can help to reduce Parkinson’s symptoms. However, these treatments are purely symptomatological and can neither halt the progress of the disease nor cure it.

Parkinson’s disease causes a lack of dopamine. L-Dopa (levodopa), the drug precursor of dopamine, is able to reach the brain, where it perform its therapeutic action.

Each patient responds differently to Parkinson’s treatment.

In addition to levodopa (L-Dopa), which remains the most effective Parkinson’s drug, dopamine agonists, MAOinhibitors, catechol-O-methyltransferases, anticholinergics, and glutamate blockers are also used in Parkinson’s treatment. Further details of each of these pharmacological treatment types can be found below:

• Levodopa (e.g. Madopar®, Sinemet®, Stalevo® = Sinemet + Entacapone, Duodopa® = levodopa + Carbidopa Gel) is the most commonly-used Parkinson’s drug and is also the most effective in treating symptoms. Taken orally, it can cross the blood-brain barrier and, once it has reached the brain, transform into dopamine.
  L-Dopa can be obtained in combinations with other active ingredients, such as carbidopa and entacapone (e.g. Levodopa/Carbidopa/Entacapone Orion); carbidopa prevents the L-Dopa from transforming into dopamine before it has reached the brain.
  The dosage must be adjusted as the disease progresses, since one of the characteristics of this drug is its progressive loss of therapeutic effectiveness over time.
  Its most common side effects include involuntary movements (dyskinesia) and orthostatic hypotension, which causes fainting fits and falls.

• Dopamine agonists (dopaminergics) are drugs whose action differs from that of L-Dopa. Rather than being converted into dopamine in the brain, they imitate dopamine’s effects by stimulating the neurons.
  The use of these drugs to treat Parkinson’s has not been shown to be effective in the long term.
  Moreover, they can have significant side effects, including hallucinations, orthostatic hypotension, water retention and sleep attacks; they may also cause obsessive-compulsive behaviors such as hypersexuality, compulsive gambling and compulsive eating. Examples of dopaminergic include Bromocriptine: Parlodel®, Cabergoline: Cabaser®, Dehydroergocryptine: Cripar®, Pergolide: Permax®, Pramipexole: Sifrol®, Ropinirole: Requip®, Rotigotine: Neupro®, Pramipexole: Mirapexin, Pramipexole Teva, Oprymea, Pramipexole Accord.
  Apomorphine (e.g. Apofin) is a dopamine agonist which can be used to provide rapid relief in the event of motor blocks.
  Amantadine (e.g. Mantadan) is a relatively weak dopamine agonist, with modest effects. It relieves tremors and rigidity, but can generate tolerance and cause confusion and hallucinations.

 

• Monoamine oxidase inhibitors (MAOIs) serve to prevent the breakdown of natural dopamine (the kind synthesized by the body) or dopamine administered in the form of L-Dopa. MAOIs have serious side effects including hallucinations, confusion, headaches and dizziness. Examples of MAOIs include Selegiline (e.g. Egibren, Jumex, Seledat).
  Rasagiline (e.g. Azilect) is a drug that blocks the enzyme monoamine oxidase-B (responsible for the breakdown of dopamine in the brain), thereby helping to reduce rigidity and slowness of movement.
  MAO-B inhibitors (enzymatic inhibitors) include Selegiline: Jumexal®, Selegilin-Helvepharm®, Selegilin-Mepha®, and Rasagiline: Azilect®.

• Catechol-O-methyltransferases are drugs used to prolong the duration of the action of levodopa-carbidopa; their interaction blocks the enzyme that destroys levodopa.
  Entacapone (e.g. Comtan, Entacapone Teva) is a drug used in combination with levodopa and carbidopa (e.g. Levodopa/Carbidopa/Entacapone Orion). It can cause confusion, dyskinesia and hallucinations.
  Tolcapone (e.g. Tasmar) is a powerful drug. During use, monitoring is required for possible liver damage. It is generally prescribed to patients who do not respond to other treatments.
  Rivastigmine (e.g. Rivastigmina Teva, Nimvastid, Prometax, Rivastigmina Actavis) is a reversible inhibitor of acetylcholinesterase.

• Anticholinergic drugs serve to control symptoms associated with Parkinson’s, especially tremor. Their therapeutic effect (reduction of tremor) must be weighed against their side effects, which include memory alteration, confusion, urinary retention, dry mouth and dry eyes. Examples of Anticholinergic drugs include benztropine (e.g. Cogentin) and trihexyphenidyl or trihex (e.g. Artane).

• Glutamate blocking drugs are used principally to treat the early symptoms of Parkinson’s.

Deep brain stimulation (DBS) is a neurosurgical procedure introduced in 1987. It consists of implanting a neurostimulator (sometimes called a “brain pacemaker”), which uses implanted electrodes to send electrical impulses to specific areas of the brain to treat movement disorders and neuropsychiatric disorders. DBS modifies brain activity in a controlled fashion and the effects are reversible.

The stimulation of certain areas of the brain has been shown to be beneficial for some disorders arising from Parkinson’s disease that do not respond well to other treatments, including essential tremor, dystonia, chronic pain, major depression, and obsessive compulsive disorder. Despite the long history of this treatment, the basic mechanism of DBS is still not clear.

Although DBS has proven effective for some patients, it is a high-risk procedure that carries with it the possibility of serious complications and side effects.

A deep brain stimulation system consists of three parts: an implantable pulse generator (IPG), the lead, and the extension. All three parts are surgically implanted inside the body.

DBS cannot cure Parkinson’s disease, but it can help to manage some symptoms. Its effect on the brain cell and neurotransmitter physiology is currently the topic of much debate, but by sending high-frequency electrical impulses into specific areas of the brain, it can mitigate symptoms and decrease the side effects caused by Parkinson’s drugs, making it possible to reduce medications or adopt a more tolerable treatment regimen.

The areas stimulated by DBS differ based on the disorder being treated. Each patient must therefore be evaluated individually and the area to be stimulated chosen based on their individual needs.

DBS surgery is extremely complex and high-risk, with complications linked to the experience of the surgical team. The principal complications include hemorrhage (1-2%) and infection (3-5%).

A healthy lifestyle and an appropriate amount of exercise make for better management of Parkinson’s disease.

Clinical studies have shown that exercise, accompanied by targeted rehabilitation treatments, can improve Parkinson’s symptoms by slowing physical decline.

Parkinson’s treatments are effective if they are performed consistently over time.

The progressive loss of motor capacity may lead to the following side effects: decreased movement leads to a progressive loss of muscle tone and decline in overall condition; the progressive loss of independence can result in a loss of self-esteem and give rise to depression; reduction in sense of balance and problems of Parkinson’s freezing and festination can cause falls.

For individuals with Parkinson’s, physical rehabilitation is therefore a crucial part of maintaining good physical condition.

Out of all of the rehabilitation treatments developed in recent years, the one which has received the most attentionfrom physicians is AMPS treatment.