Descriptions of Parkinson’s disease date back as far as 5000 BC. Around that time, an ancient Indian civilization called the disorder Kampavata and treated it with the seeds of a plant containing therapeutic levels of what is today known as levodopa. Parkinson’s disease was named after the British doctor James Parkinson, who in 1817 first described the disorder in detail as “shaking palsy.”
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative motor system disorders characterized by both motor and nonmotor features, which are the result of the loss of dopamine-producing brain cells. Parkinson’s is a progressive disease, which means that in most cases it will continue to gradually get worse. Many people who develop Parkinson’s will require nursing care. There is no cure for the disease and its exact cause is not known, but there are effective treatments that can relieve the symptoms.
Parkinson’s is the second most common age-related neurodegenerative disorder after Alzheimer’s disease, an estimated 10 million people worldwide have PD, with over 1 million people in US. The incidence of PD in the U.S. is approximately 20 cases per 100,000 people per year (60,000 per year), with the mean age of onset close to 60 years. The prevalence of PD ranges from 41 people per 100,000 in the fourth decade of life to more than 1,900 people per 100,000 among those 80 and older. Men are 1 1/2 times more likely to have Parkinson’s than women.
Idiopathic Parkinson’s (IDP)
Idiopathic Parkinson’s disease – or Parkinson’s – is the most common type of parkinsonism. Idiopathic means that the cause is unknown. Necropsy studies of patients with Parkinson’s syndrome show that idiopathic Parkinson’s disease (IPD) comprises between 60 and 75% of cases.
The main symptoms of idiopathic Parkinson’s are tremor, rigidity (stiffness) and slowness of movement.
A definitive diagnosis of IDP requires the postmortem findings of degeneration of the substantia nigra pars compacta and the presence of Lewy bodies (insoluble cytoplasmic inclusions composed of aggregated alpha-synuclein).
Vascular parkinsonism (also known as arteriosclerotic parkinsonism) affects people with restricted blood supply to the brain – usually older people who have health issues such as diabetes.
Sometimes people who have had a mild stroke may experience this form of parkinsonism.
The common symptoms of Vascular Parkonism are walking difficulties, urinary incontinence and memory problems.
The symptoms of vascular parkinsonism are often the same as normal pressure hydrocephalus, which mainly affects the lower half of the body.
Some people with vascular parkinsonism may swing their arms less than those with Parkinson’s.
A small number (around 7%) of people diagnosed with parkinsonism develop symptoms following treatment with particular medication.
Neuroleptic drugs (used to treat schizophrenia and other psychotic disorders) which block the action of dopamine are thought to be the biggest cause of drug-induced parkinsonism.
The symptoms of drug-induced parkinsonism tend to be static. Only in rare cases do they change in the manner that the symptoms of Parkinson’s do.
Most people will recover within months, and often within hours or days, of stopping the drug that is the cause.
Drugs to avoid in Parkonism
These are some (but not all) of the drugs to avoid in Parkinson’s:
Multiple System Atrophy (MSA)
Both multiple system atrophy and Parkinson’s cause stiffness and slowness of movement in the early stages.
People with multiple system atrophy can also develop symptoms such as incontinence, difficulty with swallowing and dizziness. These symptoms are unusual in early Parkinson’s.
The condition used to be known as striatonigral degeneration, Shy-Drager syndrome, or olivopontocerebellar atrophy.
Progressive Supranuclear Palsy (PSP)
Progressive supranuclear palsy affects eye movement, balance, mobility, speech and swallowing. It is sometimes called Steele-Richardson-Olszewski syndrome.
Normal Pressure Hydrocephalus
The symptoms of normal pressure hydrocephalus mainly affect the lower half of the body.
The common symptoms are walking difficulties, urinary incontinence and memory problems.
Removing some cerebrospinal fluid can help with these symptoms in the short term. If there is improvement after this procedure, an operation to divert the spinal fluid permanently (known as lumbar puncture) can help in the long term.
Stages of Parkinson’s Disease
Stage 1 is the mildest form of Parkinson’s. At this stage, there may be symptoms, but they’re not severe enough to interfere with daily tasks and overall lifestyle. In fact, the symptoms are so minimal at this stage that they’re often missed. But family and friends may notice changes in your posture, walk, or facial expressions.
A distinct symptom of stage 1 Parkinson’s is that tremors and other difficulties in movement are generally exclusive to one side of the body. Prescribed medications can work effectively to minimize and reduce symptoms at this stage.
Stage 2 is considered a moderate form of Parkinson’s, and the symptoms are much more noticeable than those experienced in stage 1. Stiffness, tremors, and trembling may be more noticeable, and changes in facial expressions can occur.
While muscle stiffness prolongs task completion, stage 2 does not impair balance. Difficulties walking may develop or increase, and the person’s posture may start to change.
People at this stage feel symptoms on both sides of the body (though one side may only be minimally affected) and sometimes experience speech difficulties.
The majority of people with stage 2 Parkinson’s can still live alone, though they may find that some tasks take longer to complete. The progression from stage 1 to stage 2 can take months or even years. And there is no way to predict individual progression.
Stage 3 is the middle stage in Parkinson’s, and it marks a major turning point in the progression of the disease. Many of the symptoms are the same as those in stage 2. However, you’re now more likely to experience loss of balance and decreased reflexes. Your movements become slower overall. This is why falls become more common in stage 3.
Parkinson’s significantly affects daily tasks at this stage, but people are still able to complete them. Medication combined with occupational therapy may help decrease symptoms.
Independence separates people with stage 3 Parkinson’s from those with stage 4. During stage 4, it’s possible to stand without assistance. However, movement may require a walker or other type of assistive device.
Many people are unable to live alone at this stage of Parkinson’s because of significant decreases in movement and reaction times. Living alone at stage 4 or later may make many daily tasks impossible, and it can be extremely dangerous.
Stage 5 is the most advanced stage of Parkinson’s disease. Advanced stiffness in the legs can also cause freezing upon standing, making it impossible to stand or walk. People in this stage require wheelchairs, and they’re often unable to stand on their own without falling. Around-the-clock assistance is required to prevent falls.
Up to 30 percent of people at stage 4 and 5 experience confusion, hallucinations, and delusions. Hallucinations occur when you see things that aren’t there. Delusions happen when you believe things that aren’t true, even when you have been presented with evidence that your belief is wrong. Dementia is also common, affecting up to 75 percent of people with Parkinson’s. Side effects from medications at these later stages can often outweigh the benefits.
Signs and Symptoms
Motor symptomatology (bradykinesia, rest tremor, rigidity, and postural disturbances)
Other non-motor symptoms may be present and may even manifest before the motor symptoms
Rapid Eye Movement
Sleep Disorders and Sleep Apnea
Mood & Personality Change
Neuropsychiatric disturbances (dementia, hallucinations and delirium) usually become evident and troublesome after several years in the course of the disease
Overt dementia; is a late complication that most frequently affects older patients with prolonged disease duration
Male erectile dysfunction
Constipation and bowel disorders
Late-onset motor symptoms include
Postural Instability & Falls
Freezing of Gait
Speech & Swallowing difficulties
Risk Factors Associated With Parkinson’s Disease
Methanol and organic solvents
High caloric intake
Increased body mass index
Inflammation associated with activation of microglia
Methcathinone (manganese content)
Nitric oxide toxicity
Formation of free radicals (e.g., hydrogen peroxide)
A substance called dopamine acts as a messenger between two brain areas – the substantia nigra and the corpus striatum – to produce smooth, controlled movements. Most of the movement-related symptoms of Parkinson’s disease are caused by a lack of dopamine due to the loss of dopamine-producing cells in the substantia nigra. When the amount of dopamine is too low, communication between the substantia nigra and corpus striatum becomes ineffective, and movement becomes impaired; the greater the loss of dopamine, the worse the movement-related symptoms. Other cells in the brain also degenerate to some degree and may contribute to non-movement related symptoms of Parkinson’s disease.
Mutations in the -synuclein gene (SNCA) in the Contursi kindred implicated this gene in Parkinson’s disease (PD). Subsequently, -synuclein was identified as the major component of Lewy bodies (cytoplasmic proteinaceous inclusions) in surviving dopaminergic neurons is the pathological hallmark of PD, and of glial cell cytoplasmic inclusions.
Genetic predisposing factors in combination with environmental factors are thought to be responsible for the cellular changes leading to progressive neuronal degeneration in which mitochondrial dysfunction, oxidative mechanisms and failure of the protein degradation machinery at the cellular level are probably involved. So far, five genes have been identified that are definitively associated with Parkinson’s disease.
SNCA (synuclein, alpha non A4 component of amyloid precursor): SNCA makes the protein alpha-synuclein. In brain cells of individuals with Parkinson’s disease, this protein aggregates in clumps called Lewy bodies. Mutations in the SNCA gene are found in early-onset Parkinson’s disease.
PARK2 (Parkinson’s disease autosomal recessive, juvenile 2): The PARK2 gene makes the protein parkin. Mutations of the PARK2 gene are mostly found in individuals with juvenile Parkinson’s disease. Parkin normally helps cells break down and recycle proteins.
PARK7 (Parkinson’s disease autosomal recessive, early onset 7): PARK7 mutations are found in early-onset Parkinson’s disease. The PARK7 gene makes the DJ-1 protein, which may protect cells from oxidative stress.
PINK1 (PTEN-induced putative kinase 1): Mutations of this gene are found in early-onset Parkinson’s disease. The exact function of the protein made by PINK1 is not known, but it may protect structures within the cell called mitochondria from stress.
LRRK2 (leucine-rich repeat kinase 2): LRRK2 makes the protein dardarin. Mutations in the LRRK2 gene have been linked to late-onset Parkinson’s disease.
Several other chromosome regions and the genes GBA (glucosidase beta acid), SNCAIP (synuclein alpha interacting protein), and UCHL1 (ubiquitin carboxyl-terminal esterase L1) may also be linked to Parkinson’s disease.
Diagnosis of Parkinson’s Disease
Bradykinesia and at least one of the following:
4–6 Hz resting tremor
Postural instability; not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction
Exclusion Criteria for PD
History of the following:
Repeated strokes with stepwise progression
Repeated head injury
Antipsychotic or dopamine-depleting drugs
Definite encephalitis and/or oculogyric crises on no drug treatment
More than 1 affected relative
Negative response to large doses of levodopa (up to 1,000-1,500 mg/day if tolerated), if malabsorption is excluded
Strictly unilateral features after 3 years
Other neurological features: supranuclear gaze palsy, cerebellar signs, early severe autonomic involvement, Babinski sign, early severe dementia with disturbances of language, memory, or praxis
Exposure to known neurotoxin
Presence of cerebral tumor or communicating hydrocephalus on neuroimaging
Features that Support a Diagnosis of PD
Three or more required for diagnosis of definite PD:
Rest tremor present
Persistent asymmetry affecting the side of onset most
Excellent (70%–100%) response to levodopa
Severe levodopa-induced chorea
Levodopa response for ≥5 years
Clinical course of ≥10 years
Treatment for Parkinson’s Disease
At present, there is no cure for PD, but a variety of medications provide dramatic relief from the symptoms. Usually, affected individuals are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of parkinsonian cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity. Other drugs, such as bromocriptine, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. In May 2006, the FDA approved rasagiline to be used along with levodopa for patients with advanced PD or as a single-drug treatment for early PD. In March 2017, the FDA approved safinamide tablets as an add-on treatment for individuals with PD how are currently taking levodopa/carbisopa and experiencing “off” episodes (when the person’s medicatins are not working well, causing an increase in PD symptoms).
In some cases, surgery may be appropriate if the disease doesn’t respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In DBS, electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work correctly.
Even if you experience symptoms common among people with PD, they may in fact be brought on by a different condition. Consult a doctor if you notice a change in your body with no obvious cause. While visiting the doctor, try to be as specific as possible when describing your symptoms. You may be referred to a movement disorders specialist; a neurologist with particular expertise in PD and other movement disorders.