Secondary Parkinson Disease
Disease Details
Family Health Simplified
- Description
- Secondary Parkinson's disease results from identifiable causes such as medications, other neurological disorders, or brain injuries, leading to symptoms similar to Parkinson's disease.
- Type
- Secondary Parkinson’s disease is not typically inherited in a genetic manner. It is caused by identifiable external factors such as medications, toxins, or other neurological conditions, rather than a genetic transmission.
- Signs And Symptoms
- The most recognizable symptoms are movement (motor) related and include tremor, bradykinesia (slowness of movement), rigidity, and shuffling/stooped gait. Non-motor symptoms, including autonomic dysfunction (dysautonomia), neuropsychiatric problems (mood, cognition, behavior or thought alterations), and sensory (especially altered sense of smell) and sleep difficulties may be present as well. People with Parkinson's disease may have non-motor symptoms that precede the onset of motor symptoms, including constipation, anosmia (inability to smell), and REM Behavior Disorder. Generally, symptoms such as dementia, psychosis, orthostasis, and more severe falls occur later. The prevalence of oropharyngeal dysphagia in PD is estimated to be as high as 82%. Dysphagia (swallowing difficulties) has been reported across all stages of the disease. Complications result from dysphagia include dehydration, malnutrition, weight loss, and aspiration pneumonia. Pneumonia is the most common cause of hospitalization and a leading cause of death in people with PD.
- Prognosis
-
PD invariably progresses with time. A severity rating method known as the Unified Parkinson's disease rating scale (UPDRS) is the most commonly used metric for a clinical study. A modified version known as the MDS-UPDRS is also used. An older scaling method known as the Hoehn and Yahr scale (originally published in 1967), and a similar scale known as the Modified Hoehn and Yahr scale, have been used. The Hoehn and Yahr scale defines five basic stages of progression.
Motor symptoms may advance aggressively in the early stages of the disease and more slowly later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and be bedridden after 10 years. Medication has improved the prognosis of motor symptoms. In people taking levodopa, the progression time of symptoms to a stage of high dependency from caregivers may be over 15 years. Predicting what course the disease will take for a given individual is difficult. Age is an appropriate predictor of disease progression. The rate of motor decline is greater in those with less impairment at the time of diagnosis, while cognitive impairment is more frequent in those who are over 70 years of age at symptom onset.No hard correlation between PD progression and PD disability as a whole has been found as of 2023; however, initial PD disability often mainly concerns the motor symptoms, whereas in later stages it is often mainly related to the non-motor symptoms of the disease. Therapies exist that can improve or alleviate these latter symptoms to some extent. As the disease advances, disability is more related to motor symptoms that are uncontrollable by medication (such as difficulties with swallowing and dysartria, and gait and balance problems) and to levodopa-induced complications, which appear in up to 50% of individuals after five years of levodopa usage. Finally, after ten years most people with the disease have autonomic disturbances, sleep problems, mood alterations and cognitive decline; these symptoms, especially cognitive decline, greatly increase disability.The life expectancy of people with PD is reduced. Mortality ratios are around twice those of unaffected people. Cognitive decline and dementia, old age at onset, a more advanced disease state, and presence of swallowing problems are all mortality risk factors. A disease pattern mainly characterized by tremor as opposed to rigidity, though, predicts an improved survival. Death from aspiration pneumonia is twice as common in individuals with PD as in the healthy population.In 2016, PD resulted in about 211,000 deaths globally, an increase of 161% since 1990. The overall death rate increased by 19% to 1.81 per 100,000 people during that time.A person with PD has two to six times the risk of dementia compared with the general population. Up to 78% of people with PD have Parkinson's disease dementia. Dementia is associated with a reduced quality of life in people with PD and their caregivers, increased mortality, and a higher probability of needing nursing home care. - Onset
- Secondary Parkinson disease has an onset that can vary widely depending on the underlying cause. Unlike idiopathic Parkinson's disease, which typically begins around age 60, secondary Parkinsonism can occur at any age after exposure to or development of the causative factor, such as medication side effects, toxins, or other neurological disorders.
- Prevalence
- The prevalence of secondary Parkinson's disease can vary depending on the underlying cause, population studied, and geographic location. Secondary Parkinson's disease results from known causes such as medications, vascular events, or other medical conditions, unlike idiopathic Parkinson's disease. Due to these varying factors, it is challenging to provide a single prevalence rate.
- Epidemiology
- PD is the second most common neurodegenerative disorder and affects approximately six million people globally. As of 2021, Parkinson's was the fastest growing neurodegenerative disease globally in both death and prevalence. The proportion in a population at a given time is about 0.3% in industrialized countries. PD is more common in the elderly and rates rise from 1% in those over 60 years of age to 4% of the population over 80. The mean age of onset is around 60 years, although 5–10% begin between the ages of 20 and 50 is classified as young onset PD. Males are affected at a ratio of around 3:2 compared with females. PD may be less prevalent in those of African and Asian ancestry (including South Asians), although this finding is disputed. The number of new diagnoses per year of PD is between 8–18 per 100,000 person–years.China is predicted to have nearly half of the Parkinson's disease population in the world in 2030. By 2040 the number of patients is expected to grow to approximately 14 million people; this growth has been referred to as the Parkinson's pandemic.The prevalence of dementia increases with age, and to a lesser degree, duration of the disease.
- Intractability
- Secondary Parkinson's disease, which results from identifiable causes such as medications, toxins, or other neurological disorders, varies in its treatability. In some cases, addressing the underlying cause can alleviate symptoms. However, if the damage to the brain is extensive or irreversible, the disease may be more challenging to manage. Treatment focuses on symptom relief, and the extent of intractability largely depends on the individual case and the success in addressing the underlying causes.
- Disease Severity
- The severity of secondary Parkinson's disease can vary widely depending on the underlying cause and how advanced the disease is. Secondary Parkinson's disease refers to parkinsonian symptoms that arise due to identifiable external factors, such as medications, stroke, brain trauma, or toxins, rather than the idiopathic Parkinson’s disease where the cause is largely unknown. The progression and severity often depend on managing the underlying cause and may not follow the same course as idiopathic Parkinson’s disease.
- Healthcare Professionals
- Disease Ontology ID - DOID:13548
- Pathophysiology
- The main pathological characteristics of PD are cell death in the brain's basal ganglia (affecting up to 70% of the dopamine-secreting neurons in the substantia nigra pars compacta by the end of life). In Parkinson's disease, alpha-synuclein becomes misfolded and clump together with other alpha-synuclein. Cells are unable to remove these clumps, and the alpha-synuclein becomes cytotoxic, damaging the cells. These clumps can be seen in neurons under a microscope and are called Lewy bodies. Loss of neurons is accompanied by the death of astrocytes (star-shaped glial cells) and an increase in the number of microglia (another type of glial cell) in the substantia nigra. Severity of progression of the parts of the brain affected by PD can be measured with Braak staging. According to this staging, PD starts in the medulla and the olfactory bulb before moving to the substantia nigra pars compacta and the rest of the midbrain/basal forebrain. Movement symptom onset is associated when the disease begins to affect the substantia nigra pars compacta.Five major pathways in the brain connect other brain areas to the basal ganglia. These are known as the motor, oculomotor, associative, limbic, and orbitofrontal circuits. Names indicate the main projection area of each circuit. All are affected in PD, and their disruption causes movement-, attention- and learning-related symptoms of the disease. Scientifically, the motor circuit has been examined the most intensively.Since 1980, a particular conceptual model of the motor circuit and its alteration with PD has been of influence although some limitations have been pointed out which have led to modifications. In this model, the basal ganglia normally exert a constant inhibitory influence on a wide range of motor systems, preventing them from becoming active at inappropriate times. When a decision is made to perform a particular action, inhibition is reduced for the required motor system, thereby releasing it for activation. Dopamine acts to facilitate this release of inhibition, so high levels of dopamine function tend to promote motor activity, while low levels of dopamine function, such as occur in PD, demand greater exertions of effort for any given movement. The result of dopamine depletion is to produce hypokinesia, an overall reduction in motor output. Drugs that are used to treat PD, conversely, may produce excessive dopamine activity, allowing motor systems to be activated at inappropriate times and thereby producing dyskinesias.
- Carrier Status
- Secondary Parkinson's disease, also known as Parkinsonism, is not typically caused by a genetic mutation and therefore does not have a "carrier status." Instead, it results from external factors such as medications, toxins, or other medical conditions.
- Mechanism
-
Secondary Parkinson disease (SPD) arises from identifiable causes other than idiopathic Parkinson's, such as toxins, drugs, infections, or other underlying disorders. The mechanisms and molecular mechanisms can be summarized as follows:
**Mechanism:**
- **Neurotoxic insults**: Exposure to certain drugs (e.g., antipsychotics, antiemetics) or neurotoxins (e.g., MPTP, carbon monoxide, manganese) can damage dopaminergic neurons in the substantia nigra.
- **Infections**: Viral or bacterial infections affecting the brain (e.g., encephalitis) can cause inflammation that damages the basal ganglia and disrupts dopamine pathways.
- **Trauma**: Repeated head injuries (e.g., in sports or accidents) can lead to chronic traumatic encephalopathy, which can manifest with parkinsonian features.
- **Vascular causes**: Multiple small strokes or a single larger stroke affecting the basal ganglia or subcortical structures can result in parkinsonism.
- **Other conditions**: Diseases like multiple system atrophy, progressive supranuclear palsy, and Wilson's disease can present with parkinsonian symptoms.
**Molecular Mechanisms:**
- **Dopamine Deficiency**: The primary molecular hallmark of SPD is the depletion or dysfunction of dopamine in the basal ganglia. This disrupts the fine-tuning of motor activity.
- **Mitochondrial Dysfunction**: Toxins like MPTP interfere with mitochondrial function, leading to neuronal death through energy failure and oxidative stress.
- **Oxidative Stress**: Oxidative damage from reactive oxygen species can exacerbate neuronal death and dysfunction in the substantia nigra.
- **Inflammation**: Neuroinflammation due to infections or brain injury can release cytokines and other inflammatory mediators that further damage dopaminergic neurons.
- **Protein Aggregation**: Misfolding and aggregation of proteins (e.g., alpha-synuclein in Lewy bodies) can occur in some cases, although less prominently than in idiopathic Parkinson's.
The interplay of these factors leads to the characteristic motor symptoms of parkinsonism, including bradykinesia, rigidity, and tremor. - Treatment
-
For secondary Parkinson's disease, treatment typically focuses on addressing the underlying cause and managing symptoms. This may include:
1. **Medications:**
- Dopaminergic medications such as Levodopa/carbidopa
- Dopamine agonists
- MAO-B inhibitors
2. **Treating underlying cause:**
- Discontinuing or adjusting drugs that may be causing symptoms
- Managing vascular risk factors if the cause is cerebrovascular disease
3. **Physical Therapy:**
- Exercises to improve mobility, balance, and strength
4. **Occupational Therapy:**
- Assistance with daily activities and safety modifications
5. **Speech Therapy:**
- Addressing speech and swallowing difficulties
6. **Lifestyle Modifications:**
- Healthy diet, regular exercise, and fall prevention strategies
It is essential to tailor the treatment plan to the individual's specific condition and needs. - Compassionate Use Treatment
-
Secondary Parkinson's disease, also known as secondary parkinsonism, is a condition with Parkinson-like symptoms typically resulting from factors such as medication side effects, toxins, or other neurological conditions. Here is information related to compassionate use treatment and off-label or experimental treatments:
1. **Compassionate Use Treatment:**
- **Levodopa-Carbidopa Intestinal Gel (LCIG):** In certain cases, this gel may be considered for compassionate use in patients who have severe motor fluctuations and are unresponsive to other treatments.
- **Deep Brain Stimulation (DBS):** While more commonly associated with primary Parkinson’s disease, DBS may be used compassionately in some secondary parkinsonism cases if symptoms are severe and other treatments have failed.
2. **Off-Label or Experimental Treatments:**
- **Amantadine:** Often used off-label to reduce dyskinesia in Parkinson's disease and may be considered for secondary parkinsonism under specialist advice.
- **Rivastigmine:** While primarily used for dementia related to Parkinson's, it may be prescribed off-label to address cognitive symptoms in secondary parkinsonism.
- **Experimental Treatments:** These may include participation in clinical trials investigating the efficacy of new pharmaceuticals or interventions specifically tailored to address the etiology and symptomatology of secondary Parkinson's disease. In this context, agents affecting neurotransmitter systems or potential neuroprotective compounds may be explored.
Each treatment option should be considered carefully by healthcare providers, taking into account the individual patient's cause of secondary parkinsonism and overall health profile. - Lifestyle Recommendations
-
For secondary Parkinson's disease, lifestyle recommendations generally focus on maintaining overall health and managing symptoms. These may include:
1. **Regular Exercise**: Engage in regular physical activity to improve mobility, balance, and strength. Activities like walking, swimming, and yoga can be beneficial.
2. **Healthy Diet**: Eat a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to promote overall health and potentially improve symptoms.
3. **Adequate Hydration**: Ensure sufficient fluid intake to avoid dehydration and maintain bodily functions.
4. **Sleep Hygiene**: Maintain a regular sleep schedule and create a restful environment to improve sleep quality.
5. **Stress Management**: Practice stress-reduction techniques such as mindfulness, meditation, or deep-breathing exercises.
6. **Social Engagement**: Stay socially active to improve mental health and cognitive function.
7. **Medication Adherence**: Follow prescribed medication regimens carefully and report any side effects to your healthcare provider.
Consult with a healthcare professional to create a personalized plan that best suits the individual's needs and circumstances. - Medication
-
For secondary Parkinson's disease, various medications may be used to manage symptoms, including:
1. **Levodopa/Carbidopa**: Often used to increase dopamine levels in the brain, which helps improve motor symptoms.
2. **Dopamine Agonists**: These mimic dopamine in the brain, examples include pramipexole and ropinirole.
3. **MAO-B Inhibitors**: Such as selegiline or rasagiline, which help prevent the breakdown of dopamine.
4. **COMT Inhibitors**: Like entacapone, which prolong the effect of levodopa therapy by inhibiting the enzyme that breaks down dopamine.
5. **Anticholinergics**: To help reduce tremors, such as benztropine.
6. **Amantadine**: An antiviral drug that can help with symptoms such as dyskinesia.
Management should be tailored to the individual's specific symptoms and needs, often involving a combination of these medications. It's crucial to consult a healthcare professional for an accurate diagnosis and appropriate treatment plan. - Repurposable Drugs
-
There are ongoing research efforts to identify repurposable drugs for secondary Parkinson's disease. Some drugs originally developed for other conditions have shown potential in treating symptoms or slowing disease progression. These include:
1. **Amantadine**: Initially used as an antiviral, it may help with motor symptoms.
2. **Rivastigmine**: Often used for dementia, it can help manage cognitive symptoms.
3. **N-Acetylcysteine (NAC)**: An antioxidant that may reduce oxidative stress in the brain.
4. **Levetiracetam**: An anti-epileptic drug that might help manage certain symptoms.
5. **Minocycline**: An antibiotic with potential neuroprotective effects.
Research is ongoing, and the effectiveness and safety of these drugs for secondary Parkinson's disease are still being evaluated. Always consult with a healthcare professional before starting any new treatment. - Metabolites
-
Secondary Parkinson's disease is not typically associated with specific metabolites that are universally recognized as biomarkers for diagnosis or monitoring. Unlike primary Parkinson's disease, which is characterized by the degeneration of dopamine-producing neurons, secondary Parkinsonism can arise due to various causes such as medications, toxins, or other underlying health conditions. Determining metabolites for secondary Parkinson's might involve identifying markers related to the specific cause rather than the disease itself. It is best to consult specific medical studies or guidelines for detailed information on potential metabolites in individual cases.
Considering your mention of "nan," if it stands for "not a number" or is used to indicate missing or undefined data, this suggests there might be no established or standard metabolites recognized for secondary Parkinson’s disease. - Nutraceuticals
-
There is limited evidence on the use of nutraceuticals for secondary Parkinson's disease, which is often caused by external factors such as medication or environmental toxins. Some nutraceuticals that might be considered include:
1. **Coenzyme Q10 (CoQ10)**: An antioxidant which some studies suggest could have neuroprotective effects.
2. **Omega-3 fatty acids**: These may help reduce inflammation and support brain health.
3. **Vitamin D**: Deficiency in Vitamin D is common in Parkinson's patients, and supplementation could potentially support overall health.
4. **Curcumin**: Found in turmeric, curcumin has anti-inflammatory properties that might benefit brain health.
However, more research is needed to determine their efficacy and safety specifically for secondary Parkinson's disease. Always consult with a healthcare professional before starting any new treatment. - Peptides
-
Secondary Parkinson's disease, also known as atypical Parkinsonism, refers to conditions that cause Parkinsonian symptoms but are due to known causes other than idiopathic Parkinson's disease. These causes could include medication side effects, toxic exposures, or other neurological diseases.
Peptides: Research is ongoing to explore the role of peptides in the treatment of Parkinson's disease. Peptides can influence brain health, neuroprotection, and potentially slow disease progression. Some studies investigate peptide vaccines or peptide-based therapies to modulate the immune system or enhance neuronal survival.
Nanotechnology (Nan): Nanotechnology has emerging applications in Parkinson's disease, focusing on improving drug delivery, diagnostics, and neuroprotection. Nanoparticles can be engineered to cross the blood-brain barrier, providing targeted delivery of therapeutic agents directly to the brain. This can enhance the efficacy of treatments while minimizing side effects. Additionally, nanotechnology-based diagnostics are being developed for early and more accurate detection of Parkinsonian disorders.
These approaches are mostly in experimental stages, and their potential impact on secondary Parkinson's disease specifically is an area of active investigation.