12.4 Parkinson's disease and movement disorders
4 min read•august 15, 2024
is a neurodegenerative disorder that messes with your movement. It's like your brain's center is on the fritz, causing shaky hands, stiff muscles, and slow movements. But it's not just about physical symptoms - it can mess with your mind too.
This section dives into the nitty-gritty of Parkinson's and other movement disorders. We'll look at what causes them, how they're diagnosed, and ways to manage the symptoms. It's all about understanding how our brains control movement and what happens when things go wrong.
Parkinson's Disease: Clinical Features and Diagnosis
Motor Symptoms and Non-Motor Manifestations
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- Progressive neurodegenerative disorder characterized by cardinal motor symptoms
- : slowness of movement
- : stiffness and increased muscle tone
- : involuntary shaking, typically in the hands (pill-rolling tremor)
- : impaired balance and coordination
- Non-motor symptoms may include cognitive impairment, depression, sleep disturbances, autonomic dysfunction (constipation, urinary problems), and olfactory dysfunction
Diagnostic Criteria and Differential Diagnosis
- Diagnosis based on clinical criteria
- Presence of cardinal motor symptoms
- Exclusion of other potential causes (vascular parkinsonism, drug-induced parkinsonism, )
- No definitive diagnostic test for Parkinson's disease
- (DaTscan) can assess dopaminergic function but not specific to Parkinson's disease
- Response to supports diagnosis but not definitive
Other Common Movement Disorders
-
- Rhythmic, oscillatory tremor affecting hands, head, voice, and legs
- Often hereditary and exacerbated by stress, fatigue, and certain medications
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- Sustained or intermittent muscle contractions causing abnormal movements or postures
- Can be focal (affecting one body part), segmental (affecting adjacent body parts), or generalized
- May be genetic (DYT1 dystonia) or acquired (drug-induced, brain injury)
-
- Inherited neurodegenerative disorder caused by in huntingtin gene
- Progressive motor (chorea), cognitive (dementia), and psychiatric symptoms (depression, irritability)
- Less common movement disorders
- : parkinsonism with early postural instability, supranuclear gaze palsy, and cognitive impairment
- Multiple system atrophy: parkinsonism with autonomic dysfunction, cerebellar ataxia, and pyramidal signs
- : asymmetric parkinsonism, apraxia, cortical sensory loss, and alien limb phenomenon
Parkinson's Disease: Neuropathological Changes
Dopaminergic Neuron Loss and Lewy Bodies
- Progressive loss of dopaminergic neurons in pars compacta
- Leads to depletion in striatum and disruption of function
- Extent of neuron loss correlates with severity of motor symptoms
- Estimated 50-70% of dopaminergic neurons lost by the time motor symptoms manifest
- Presence of : intracellular inclusions containing aggregated alpha-synuclein protein
- Pathological hallmark of Parkinson's disease
- Also found in other brain regions (, , cortex)
Pathogenic Mechanisms and Non-Dopaminergic Involvement
- , , and contribute to
- Non-dopaminergic brain regions also affected, contributing to non-motor symptoms
- Cholinergic neurons in : cognitive impairment
- Noradrenergic neurons in locus coeruleus: sleep disturbances, autonomic dysfunction
- Serotonergic neurons in raphe nuclei: depression, anxiety
- Neuropathological changes in other movement disorders
- Huntington's disease: selective loss of medium spiny neurons in striatum
- Multiple system atrophy: degeneration of striatum, cerebellum, and autonomic nervous system
Risk Factors for Parkinson's Disease and Movement Disorders
Genetic Factors
- Familial forms of Parkinson's disease associated with mutations in specific genes
- SNCA: encodes alpha-synuclein, main component of Lewy bodies
- LRRK2: encodes leucine-rich repeat kinase 2, involved in neuronal survival and function
- PRKN, PINK1, DJ-1: involved in mitochondrial function and oxidative stress response
- Huntington's disease: autosomal dominant disorder caused by CAG trinucleotide repeat expansion in huntingtin gene
- Length of CAG repeat inversely correlated with age of onset
- Essential tremor: strong genetic component, often autosomal dominant inheritance
- Dystonia: can be genetic (DYT1 mutation) or acquired
Environmental and Age-Related Factors
- Exposure to pesticides, herbicides, and heavy metals associated with increased risk of Parkinson's disease
- Specific causal relationships remain unclear
- Examples: , ,
- Age is the greatest risk factor for Parkinson's disease
- Incidence increases significantly after age 60
- May be related to age-associated changes (oxidative stress, decreased neurotrophic support)
- Head trauma and traumatic brain injury associated with increased risk of Parkinson's disease and chronic traumatic encephalopathy (CTE)
- Protective factors: caffeine consumption, smoking (although not recommended due to other health risks)
Managing Parkinson's Disease: Interventions
Pharmacological Treatments
- Levodopa: dopamine precursor, most effective for managing motor symptoms
- Combined with carbidopa to prevent peripheral metabolism and increase CNS availability
- Long-term use associated with motor complications (dyskinesias, on-off fluctuations)
- Dopamine agonists: directly stimulate dopamine receptors
- Examples: pramipexole, ropinirole
- Used as monotherapy or in combination with levodopa
- May have fewer motor complications but more side effects (impulse control disorders, hallucinations)
- Monoamine oxidase B (MAO-B) inhibitors: increase dopamine levels by inhibiting breakdown
- Examples: selegiline, rasagiline
- May provide neuroprotective effects and delay need for levodopa
Surgical and Non-Pharmacological Interventions
- (DBS): surgical implantation of electrodes to modulate abnormal neural activity
- Targets: subthalamic nucleus, globus pallidus
- Improves motor symptoms in advanced Parkinson's disease
- Risks include infection, hemorrhage, and stimulation-related side effects
- Physical therapy, occupational therapy, and speech therapy
- Improve mobility, daily functioning, and communication
- Examples: gait training, balance exercises, voice amplification devices
- Cognitive-behavioral therapy and support groups
- Address psychological and social impact of Parkinson's disease
- Improve coping strategies and quality of life
Interventions for Other Movement Disorders
- Essential tremor: medications (propranolol, primidone, topiramate), DBS, focused ultrasound thalamotomy
- Dystonia: botulinum toxin injections, anticholinergic drugs (trihexyphenidyl), DBS
- Huntington's disease: symptomatic management (antipsychotics, antidepressants, tetrabenazine for chorea), supportive care
- Parkinson-plus syndromes (PSP, MSA, CBD): symptomatic treatment, supportive care, clinical trials for disease-modifying therapies
Key Terms to Review (38)
Acetylcholine: Acetylcholine is a neurotransmitter that plays a critical role in transmitting signals between nerve cells and muscles, as well as in various brain functions. It is involved in several important processes, including muscle contraction, memory formation, and modulation of attention, making it essential for both motor control and cognitive functions.
Activities of daily living: Activities of daily living (ADLs) refer to the basic tasks essential for self-care and daily functioning, such as bathing, dressing, eating, toileting, and mobility. These activities are crucial indicators of a person's functional status and independence. The ability to perform ADLs can be significantly impacted by various neurological conditions, which can lead to a decline in cognitive and motor skills.
Basal ganglia: The basal ganglia is a group of interconnected brain structures that play a crucial role in coordinating voluntary movements, motor control, and procedural learning. These structures are important for regulating the initiation and execution of movement and are also involved in cognitive functions such as emotion and reward processing, making them key players in both movement and behavior.
Bradykinesia: Bradykinesia is a term used to describe the slowness of movement, which is a key feature of various movement disorders. This symptom significantly impacts the ability to initiate and perform voluntary movements, leading to difficulties in everyday activities such as walking, dressing, and speaking. Bradykinesia is often associated with conditions affecting the basal ganglia, particularly in the context of neurodegenerative diseases like Parkinson's disease.
Cag trinucleotide repeat expansion: CAG trinucleotide repeat expansion refers to a genetic phenomenon where the DNA sequence 'CAG' is repeated multiple times within a gene, leading to abnormal protein function and various neurodegenerative disorders. This expansion is particularly notable in disorders such as Huntington's disease, where the excessive repetition results in a toxic gain of function in the huntingtin protein, contributing to neuronal degeneration and movement disorders.
Corticobasal degeneration: Corticobasal degeneration is a rare neurodegenerative disorder characterized by progressive degeneration of the cerebral cortex and the basal ganglia, leading to movement and cognitive impairments. This condition often presents with symptoms similar to Parkinson's disease but includes distinct features such as asymmetric motor symptoms and cortical dysfunction, highlighting its unique impact on brain function.
Deep brain stimulation: Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes in specific areas of the brain to deliver electrical impulses. This technique is primarily used to treat movement disorders, particularly Parkinson's disease, by modulating the abnormal neural circuits that contribute to symptoms like tremors and rigidity. DBS has gained recognition for its ability to improve motor functions and enhance the quality of life for individuals suffering from these conditions.
Dj-1 gene: The dj-1 gene encodes a protein that is involved in protecting neurons from oxidative stress and has been linked to the pathogenesis of Parkinson's disease. Mutations in this gene are associated with a rare, autosomal recessive form of early-onset Parkinson's disease, highlighting its crucial role in neuronal survival and function.
Dopamine: Dopamine is a neurotransmitter that plays a crucial role in sending messages between nerve cells in the brain, influencing mood, motivation, and movement. It is involved in many essential functions such as reward processing, motor control, and regulating emotional responses, making it a key player in various aspects of brain function.
Dopaminergic neuron loss: Dopaminergic neuron loss refers to the degeneration and death of neurons that produce dopamine, a crucial neurotransmitter involved in movement, motivation, and reward. This loss is particularly significant in the context of certain movement disorders, where it leads to symptoms such as tremors, stiffness, and difficulties with coordination and balance, notably observed in Parkinson's disease.
Dystonia: Dystonia is a movement disorder characterized by sustained muscle contractions, abnormal postures, and twisting movements. This condition can impact any part of the body, causing discomfort and interfering with normal movements. Dystonia is often linked to abnormalities in the basal ganglia, a group of structures in the brain that are crucial for coordinating movement, making it a key element in understanding various movement disorders, especially those associated with conditions like Parkinson's disease.
Dyt1 gene: The dyt1 gene is a specific genetic mutation associated with early-onset dystonia, a movement disorder characterized by involuntary muscle contractions and abnormal postures. This gene is crucial in understanding how genetic factors contribute to the development of movement disorders like dystonia, particularly in the context of Parkinson's disease and other related conditions. The mutation in the dyt1 gene can lead to disruptions in the normal functioning of neurotransmitters, affecting motor control.
Essential Tremor: Essential tremor is a neurological disorder characterized by involuntary and rhythmic shaking, typically affecting the hands, arms, head, or voice. This condition is often mistaken for Parkinson's disease, but essential tremor is distinct as it usually occurs during movement and is not associated with the same severity of rigidity or bradykinesia. The tremors can worsen over time and significantly impact daily activities, making understanding this disorder important in the context of movement disorders.
Huntington's Disease: Huntington's disease is a hereditary neurodegenerative disorder characterized by the progressive breakdown of nerve cells in the brain, leading to motor dysfunction, cognitive decline, and psychiatric symptoms. This disease primarily affects areas of the brain such as the cerebral cortex and subcortical structures, particularly the basal ganglia, which play a critical role in movement control.
Levodopa: Levodopa is a medication that serves as a precursor to dopamine, primarily used to treat Parkinson's disease. By replenishing dopamine levels in the brain, it helps improve motor control and reduce symptoms such as tremors and rigidity. Its connection to basal ganglia functions is crucial, as the basal ganglia are involved in the regulation of movement, which is disrupted in movement disorders like Parkinson's disease.
Lewy bodies: Lewy bodies are abnormal aggregates of protein that develop inside nerve cells, primarily consisting of alpha-synuclein. These structures are notably associated with neurodegenerative disorders, particularly Parkinson's disease and Lewy body dementia. Their presence disrupts normal cell function, leading to cell death and contributing to the movement and cognitive symptoms observed in these diseases.
Locus coeruleus: The locus coeruleus is a small, dark blue nucleus located in the pons of the brainstem that plays a crucial role in the regulation of arousal and stress responses. It is the primary source of norepinephrine in the brain, influencing mood, attention, and alertness. Its involvement in various neural pathways connects it to several conditions, including Parkinson's disease and other movement disorders.
Lrrk2 gene: The lrrk2 gene encodes for a protein called leucine-rich repeat kinase 2, which is implicated in various cellular processes, including neuronal signaling and inflammation. Mutations in this gene are one of the most common genetic contributors to Parkinson's disease, linking it directly to movement disorders and the degeneration of dopaminergic neurons in the brain.
Manganese: Manganese is a trace mineral that plays an essential role in various bodily functions, particularly in the context of brain health and movement control. It acts as a cofactor for several enzymes involved in metabolism and is crucial for the production of neurotransmitters, which are vital for communication between nerve cells. However, excessive exposure to manganese, especially through environmental sources, can lead to neurological disorders resembling Parkinson's disease.
Mitochondrial dysfunction: Mitochondrial dysfunction refers to the impairment of the mitochondria, which are the powerhouses of the cell responsible for generating energy in the form of ATP. This condition is often associated with various neurodegenerative diseases and movement disorders, impacting cellular metabolism and leading to an array of symptoms such as fatigue, muscle weakness, and cognitive decline. In the context of certain disorders, mitochondrial dysfunction contributes to the degeneration of dopaminergic neurons, which is particularly relevant in conditions characterized by movement impairments.
Motor control: Motor control refers to the processes and systems that govern the planning, execution, and coordination of voluntary movements. It involves a complex interplay between various brain regions, including the cerebral cortex and subcortical structures, as well as peripheral mechanisms such as reflexes and central pattern generators. This term is crucial for understanding movement disorders, particularly those linked to the basal ganglia and specific conditions like Parkinson's disease.
Multiple system atrophy: Multiple system atrophy is a rare, progressive neurodegenerative disorder characterized by a combination of symptoms affecting movement, balance, and autonomic functions. It is often considered a type of movement disorder related to Parkinson's disease due to overlapping symptoms, yet it presents unique challenges such as early onset of severe autonomic dysfunction and atypical parkinsonism.
Neuroimaging: Neuroimaging refers to a range of techniques used to visualize the structure and function of the brain. These methods allow researchers and clinicians to observe brain activity and identify abnormalities or changes in brain structure that are associated with various neurological conditions. By providing insights into how different areas of the brain are activated during tasks or how they are affected by diseases, neuroimaging plays a crucial role in understanding language disorders, consciousness, dementias, and movement disorders.
Neuroinflammation: Neuroinflammation is the inflammatory response within the brain or spinal cord, typically triggered by injury, infection, or disease. This process involves the activation of glial cells, such as microglia and astrocytes, which can release pro-inflammatory cytokines that may contribute to neuronal damage. Neuroinflammation is increasingly recognized as a key factor in various neurodegenerative diseases, including Parkinson's disease, where it can exacerbate motor and cognitive dysfunction.
Nucleus basalis of Meynert: The nucleus basalis of Meynert is a group of neurons located in the basal forebrain, primarily involved in the production of acetylcholine, a neurotransmitter that plays a crucial role in attention, learning, and memory. This area is closely connected to the cerebral cortex and is particularly important for cognitive functions, which can be affected in various neurodegenerative diseases such as Alzheimer's and Parkinson's.
Oxidative stress: Oxidative stress is an imbalance between free radicals and antioxidants in the body, leading to cellular damage. This condition occurs when there are too many free radicals or not enough antioxidants to neutralize them, which can cause inflammation and damage to DNA, proteins, and lipids. In the context of neurological disorders, such as Parkinson's disease, oxidative stress plays a significant role in neuronal degeneration and contributes to the progression of movement disorders.
Paraquat: Paraquat is a toxic herbicide commonly used to control weeds and grasses. It is associated with environmental and health risks, particularly in relation to neurodegenerative diseases such as Parkinson's disease. Its connection to these conditions arises from studies showing that exposure to paraquat may increase the risk of developing Parkinson's due to its neurotoxic effects on dopamine-producing neurons in the brain.
Parkinson's Disease: Parkinson's disease is a progressive neurological disorder that primarily affects movement, causing tremors, stiffness, and difficulty with balance and coordination. It arises from the degeneration of dopamine-producing neurons in a specific area of the brain, significantly impacting the communication between various structures involved in motor control and behavior.
Pink1 gene: The pink1 gene is a crucial gene associated with the regulation of mitochondrial function and has been linked to the development of Parkinson's disease. It encodes a protein that protects cells from stress-induced mitochondrial dysfunction, which is particularly important in neurons that are susceptible to damage. Mutations in the pink1 gene can lead to early-onset Parkinson's disease, highlighting its role in movement disorders.
Postural Instability: Postural instability refers to a condition where an individual has difficulty maintaining an upright posture and balance, often leading to falls. This symptom is particularly prominent in certain movement disorders, indicating dysfunction in the neural pathways that help control posture and balance, especially involving the basal ganglia. Understanding postural instability is crucial for comprehending how it impacts daily living and mobility in individuals with specific neurological conditions.
Prkn gene: The prkn gene, also known as the Parkin gene, encodes a protein that plays a critical role in the ubiquitin-proteasome system, which helps regulate protein degradation and maintain cellular health. Mutations in this gene are linked to early-onset Parkinson's disease and contribute to the dysfunction of dopamine-producing neurons, leading to the characteristic motor symptoms associated with movement disorders.
Progressive supranuclear palsy: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder characterized by the gradual loss of control over movement, eye coordination, and balance. It often resembles Parkinson's disease, but differs in symptoms and progression, leading to distinct challenges in diagnosis and treatment. PSP is caused by the degeneration of brain cells, particularly in areas that control movement and balance.
Raphe nuclei: The raphe nuclei are a cluster of nuclei located in the brainstem that are primarily involved in the production and release of serotonin. These nuclei play a significant role in regulating mood, arousal, and various physiological functions, connecting them to several neurological and psychological disorders.
Resting tremor: A resting tremor is an involuntary, rhythmic shaking of a body part that occurs when the muscles are relaxed and at rest. This type of tremor is commonly associated with Parkinson's disease and is one of the hallmark symptoms used to diagnose movement disorders. Resting tremors typically affect the hands, arms, legs, and even the jaw, and they often diminish or disappear during voluntary movement.
Rigidity: Rigidity is a condition characterized by increased muscle tone, leading to stiffness and resistance to passive movement. This phenomenon is often observed in movement disorders where the ability to control muscle tone is compromised, affecting the coordination and fluidity of voluntary movements.
Rotenone: Rotenone is a naturally occurring compound extracted from the roots of certain plants, primarily used as a pesticide and insecticide. In the context of neuroscience, it is significant because rotenone is known to induce Parkinson's disease-like symptoms in animal models by inhibiting mitochondrial function, which ultimately leads to the death of dopamine-producing neurons, a hallmark of Parkinson's disease.
Snca gene: The snca gene encodes for alpha-synuclein, a protein that plays a crucial role in synaptic function and neurotransmitter release. Abnormal accumulation of alpha-synuclein is a hallmark of Parkinson's disease and other neurodegenerative disorders, linking the gene directly to movement disorders and contributing to the understanding of their pathology.
Substantia Nigra: The substantia nigra is a crucial structure located in the midbrain that plays a key role in movement regulation and reward. It is part of the basal ganglia and contains neurons that produce dopamine, which is essential for coordinating smooth and controlled movements. The health of the substantia nigra is vital, as its degeneration is linked to several movement disorders.