is a complex neurological disorder affecting movement and cognition. It's caused by the loss of -producing brain cells, leading to symptoms like tremors, stiffness, and slow movement. Understanding its mechanisms is crucial for developing effective treatments.
Diagnosis involves clinical assessment, brain scans, and response to medication. While there's no cure, treatments can manage symptoms and improve quality of life. Ongoing research aims to uncover the root causes and develop new therapies for this challenging condition.
Pathophysiology and Clinical Presentation of Parkinson's Disease
Mechanisms of Parkinson's disease
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Degeneration of dopaminergic neurons in the pars compacta (SNpc)
Leads to decreased dopamine levels in the (caudate nucleus and putamen)
Disrupts the balance of the circuitry, affecting motor control and movement initiation
Accumulation of abnormal protein aggregates called
Primarily composed of misfolded protein, which contributes to neuronal dysfunction and cell death
Found in surviving neurons of the SNpc and other brain regions (cortex, amygdala, locus coeruleus)
Impairment of the
Affects the initiation and control of voluntary movements, resulting in motor symptoms (, , )
Caused by the loss of dopaminergic neurons projecting from the SNpc to the striatum
Neurotransmitter imbalances
Reduced dopamine levels lead to increased activity of the indirect pathway (inhibitory), resulting in excessive inhibition of the thalamus and
Decreased activity of the direct pathway (excitatory), further contributing to the motor symptoms of Parkinson's disease
Imbalance between dopamine and other (, , ) in the basal ganglia
Symptoms of Parkinson's disease
Motor symptoms
Bradykinesia: slowness of movement, difficulty initiating and executing tasks (buttoning shirts, tying shoelaces)
Rigidity: stiffness of muscles, resistance to passive movement, often described as "lead-pipe" or "cogwheel" rigidity
Resting tremor: typically unilateral, 4-6 Hz frequency, most prominent in the hands ("pill-rolling" tremor) and less common in the legs or jaw
: impaired balance and coordination, increased risk of falls, especially in later stages of the disease
Gait disturbances: shuffling gait, reduced arm swing, difficulty turning, and freezing of gait (sudden, brief inability to move)
Non-motor symptoms
Cognitive impairment and dementia: difficulty with attention, executive function, and memory, increased risk of developing dementia in advanced stages
Depression and anxiety: common mood disorders that can precede motor symptoms and affect quality of life
Sleep disorders: (acting out dreams), insomnia, excessive daytime sleepiness
Autonomic dysfunction: (drop in blood pressure upon standing), constipation, urinary frequency or urgency
Olfactory dysfunction: reduced sense of smell (), often an early non-motor symptom
Physical signs
Masked facial expression (): reduced facial muscle movement, leading to a "poker face" appearance
: small, cramped handwriting that becomes progressively smaller and more difficult to read
Soft and monotonous speech (): reduced volume and lack of inflection in speech
Drooling (): due to reduced swallowing frequency and impaired control of oral and pharyngeal muscles
Stooped posture and festinating gait: flexed posture and short, shuffling steps with a tendency to accelerate while walking
Causes and diagnosis of Parkinson's
Potential causes
Genetic factors
Familial Parkinson's disease: accounts for 5-10% of cases, with mutations in genes (, , , , )
Genetic susceptibility: certain genetic variations increase the risk of developing Parkinson's disease
Environmental factors
Exposure to pesticides, herbicides, and heavy metals (rotenone, paraquat, manganese)
Rural living and well-water consumption, possibly due to increased exposure to environmental toxins
Aging
Increased risk with advancing age, with an average age of onset around 60 years
Age-related changes in the brain may contribute to the development of Parkinson's disease
Diagnostic methods
Clinical assessment
Detailed medical history and neurological examination to assess motor symptoms and exclude other conditions
Assessment of motor symptoms using the (UPDRS), which evaluates speech, facial expression, tremor, rigidity, bradykinesia, and postural stability
Neuroimaging techniques
Dopamine transporter (DaT) scan using single-photon emission computed tomography (SPECT): assesses the integrity of dopaminergic neurons in the striatum, helping to differentiate Parkinson's disease from essential tremor and drug-induced parkinsonism
Magnetic resonance imaging (MRI) and computed tomography (CT): rule out other causes of parkinsonism (vascular parkinsonism, multiple system , normal pressure hydrocephalus)
test
Administering levodopa, a dopamine precursor, to observe the patient's response
Significant improvement in motor symptoms (>30% reduction in UPDRS score) supports the diagnosis of Parkinson's disease
Exclusion of other causes of parkinsonism
Essential tremor: typically involves action tremor rather than resting tremor and does not respond to levodopa
Drug-induced parkinsonism: caused by dopamine-blocking medications (antipsychotics, antiemetics) and resolves upon discontinuation of the offending drug
Progressive supranuclear palsy: characterized by early postural instability, supranuclear gaze palsy, and poor response to levodopa
Corticobasal degeneration: presents with asymmetric apraxia, cortical sensory loss, and alien limb phenomenon, in addition to parkinsonism
Historical and Cellular Aspects of Parkinson's Disease
First described by in 1817 in his "Essay on the Shaking Palsy"
in Parkinson's disease primarily affects dopaminergic neurons in the substantia nigra
contributes to the progressive loss of dopaminergic neurons
plays a role in the pathogenesis of Parkinson's disease
Impaired function of the motor cortex results from the loss of dopaminergic input