Parkinson's disease

Parkinson's disease
Name	Parkinson's disease
Synonyms	Parkinson disease, PD, paralysis agitans, shaking palsy
Caption	Substantia nigra showing loss of pigmented dopaminergic neurons, a hallmark.
Field	Neurology
Symptoms	Tremor, bradykinesia, rigidity, postural instability
Complications	Dementia, depression, anxiety
Onset	Age > 60 typically
Duration	Chronic
Causes	Unknown (idiopathic)
Risks	Ageing, genetics, pesticide exposure
Diagnosis	Based on symptoms, neurological examination
Differential	Essential tremor, dementia with Lewy bodies, multiple system atrophy
Treatment	Levodopa, dopamine agonists, deep brain stimulation
Medication	Carbidopa/levodopa, ropinirole, pramipexole
Prognosis	Progressive, life expectancy reduced
Frequency	~1% over age 60

Parkinson's disease is a chronic, progressive neurodegenerative disorder primarily affecting motor function. It is classically characterized by a quartet of cardinal motor signs. The underlying pathology involves the degeneration of dopamine-producing neurons in a specific region of the midbrain.

Signs and symptoms

The primary motor manifestations include a resting tremor often beginning in a hand, described as "pill-rolling," bradykinesia which is slowness of movement, muscle rigidity, and postural instability leading to falls. Non-motor symptoms are prevalent and can precede motor signs by years, including anosmia, rapid eye movement sleep behavior disorder, constipation, and orthostatic hypotension. Neuropsychiatric features such as depression, anxiety, apathy, and later cognitive impairment progressing to dementia are common. Other complications involve dysphagia, hypophonia, micrographia, and a characteristic shuffling gait known as festination.

Causes

The majority of cases are idiopathic, with no single identified cause. Established risk factors include advanced age, the most significant non-genetic factor, and exposure to certain environmental toxins like specific pesticides (e.g., rotenone, paraquat) and herbicides. A minority of cases, particularly those with early onset, are linked to genetic mutations. Notable genes implicated include SNCA (encoding alpha-synuclein), LRRK2, PARK7, PINK1, and PRKN. Family history increases risk, and several genetic loci have been identified through genome-wide association studies.

Pathophysiology

The central pathological process is the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra within the basal ganglia. This depletion disrupts the normal circuitry of the cortico-basal ganglia-thalamo-cortical loop, leading to excessive inhibitory output from the globus pallidus internus and substantia nigra pars reticulata. The hallmark histopathological feature is the presence of intracellular inclusions called Lewy bodies, primarily composed of aggregated alpha-synuclein protein. This synucleinopathy is thought to propagate through the brain in a stereotypical pattern, described by the Braak staging.

Diagnosis

Diagnosis remains primarily clinical, based on history and neurological examination identifying the cardinal motor features. The United Kingdom Parkinson's Disease Society Brain Bank Criteria and the Movement Disorder Society clinical diagnostic criteria are widely used. Neuroimaging techniques like DaTscan (dopamine transporter scan) can help differentiate it from essential tremor or drug-induced parkinsonism but are not routinely required. Magnetic resonance imaging is typically normal but helps rule out other conditions like vascular parkinsonism or normal pressure hydrocephalus. Differential diagnoses include multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration.

Management

There is no cure, so management focuses on symptom control. The mainstay of pharmacological treatment is levodopa, almost always combined with carbidopa (Sinemet) to reduce peripheral side effects. Other medications include dopamine agonists (ropinirole, pramipexole), MAO-B inhibitors (selegiline, rasagiline), and COMT inhibitors (entacapone). For advanced cases with motor fluctuations, device-aided therapies like deep brain stimulation targeting the subthalamic nucleus or globus pallidus internus, and levodopa-carbidopa intestinal gel infusion are options. Non-pharmacological approaches are critical and include physical therapy, occupational therapy, and speech therapy.

Prognosis

It is a progressive disorder; the rate of progression varies significantly between individuals. While not directly fatal, it leads to increasing disability and complications such as pneumonia from aspiration, sepsis from pressure injuries, and fatal falls, which reduce life expectancy. The development of dementia and psychosis are poor prognostic indicators. The Hoehn and Yahr scale and the Unified Parkinson's Disease Rating Scale are used to track clinical progression and disability.

Epidemiology

It is the second most common neurodegenerative disorder after Alzheimer's disease. Prevalence increases dramatically with age, affecting approximately 1% of the population over 60 years and up to 4% of those over 80. Incidence is about 8 to 18 per 100,000 person-years. It is slightly more common in men than women by a ratio of about 3:2. Geographic and ethnic variations exist, with higher reported prevalence in Europe and North America, though this may reflect diagnostic and reporting differences.

Category:Parkinson's disease Category:Neurodegenerative disorders Category:Movement disorders