Overview Parkinson’s disease is a progressive neurodegenerative disorder characterised by tremor, rigidity, bradykinesia, and a wide spectrum of non-motor symptoms including sleep disorders, hyposmia, bladder and bowel dysfunction, fatigue, dementia, and other neuropsychiatric symptom. Although the disease has no cure, available treatments effectively control motor symptoms and improve quality of life. Parkinson disease affects approximately 1 percent of persons older than 60 years, and up to 4 percent of those older than 80 years.
|Remember Parkinson’s disease should be suspected in someone with tremor, stiffness, slowness, balance problems, or gait disorders|
Parkinson’s Disease: Progressive, degenerative brain disease that causes trembling, stiffness, slowness of movement and a loss of fine motor control.
Idiopathic Parkinson’s disease: or Parkinson’s – is the most common type of parkinsonism. Unlike some other forms which have specific causes it is not known why idiopathic Parkinson’s occurs. Idiopathic means that the cause is unknown.
Parkinsonism: Umbrella term that describes many conditions which share some of the symptoms of Parkinson’s. The main symptoms of Parkinson’s – tremor, rigidity and slowness of movement – are also the main symptoms of a number of conditions that are grouped together under the term parkinsonism
Akinetic Rigid Syndrome: Defined by paucity and slowness of movement accompanied by muscle stiffness and resistance to passive movement. The akinetic–rigid syndrome is typical of idiopathic Parkinson’s disease, so is often described as the syndrome of parkinsonism.
Signs and Symptoms
|Four Cardinal Signs of Parkinson’s: Resting Tremor, Bradykinesia, Rigidity and postural Instability.|
Pre-motor features of PD
- Disorders of smell
- Sleep disorders
- Speech disorders
- Autonomic disorders
- Memory changes
- Mood changes
- Sensory changes
4 cardinal motor symptoms (more info below)
- Resting Tremor
- Postural instability (late finding)
- Disappears with voluntary movement and sleep
- 30% no tremor at onset (Most develop as disease progresses)
- Single arm or leg at onset, becoming bilateral
- Commonly disabling in the early stages
- Problems with fine motor tasks: writing, sewing or getting dressed.
- Decreased blink rate (abnormal glabellar reflex)
- Modified by activity or emotional state
- Some barely able to walk yet may run if frighten
- Generally less difficulty when some sort of external cue is provided
|Glabellar reflex is a primitive reflex. It is elicited by repetitive tapping on the forehead. The tapping causes the person to blink but after a while blinking stops. In Parkinson’s Disease blinking persists.|
Rigidity (Stiff joints)
- Lead-pipe rigidity
- Cogwheel rigidity
- Asymmetrical, neck and shoulder muscles prior to face and extremities.
- With progression, affects the whole body and reduces the ability to move.
- Joint pain is often an initial manifestation of PD
- Late stages with impaired balance/falls
- Diminished arm swing
- Retropulsion, inability to stop
- Gait festination
- rapid shuffling steps and a forward-flexed posture when walking
Non-motor signs/Autonomic dysfunction
- Can occur years before diagnosis
- Orthostatic hypotension, excessive sweating, urinary incontinence and altered sexual function
- Constipation and gastric dysmotility
- Double vision
- Impaired smell, paresthesias
Tremor, often combined with slowness and stiffness in an arm, presents frequently in general practice. It may be caused by essential tremor, which affects 2-3% of the population. Differentiating essential tremor from Parkinson’s disease can be difficult, even for experienced physicians.
Essential tremor (ET)
- ET 10 times more prevalent than PD.
- ET is a postural ± action tremor. A severe postural tremor may be present at rest but is not ‘pill rolling’.
- Patients with ET may also have: vocal tremor; head tremor (‘no–no’ or ‘yes–yes’).
- In PD there may be: jaw tremor; leg rest tremor.
|CONDITION||HISTORY||SIGNS AND SYMPTOMS||RADIOGRAPHIC FINDING|
|Idiopathic Parkinson’s disease||Difficulty with tasks, rigidity, tremor||Resting tremor, rigidity, bradykinesia||No specific CT or MRI findings|
|Drug-induced parkinsonism||Previous use of a causative drug such as an antipsychotic, reserpine or metoclopramide||Tremor, rigidity, bradykinesia; often bilateral symptoms||None|
|Vascular parkinsonism||Stepwise progression; CVA or TIA, comorbid cardiovascular disease||Fixed deficits from previous events||Lesions in white matter +/- basal ganglia|
|Essential tremor||History in multiple family members, little evolution||Tremor often is action-based; absence of extrapyramidal symptoms (except possible mild rigidity); no response to levodopa; tremor often is bilateral and can be attenuated by alcohol||SPECT shows normal dopaminergic system|
|Normal-pressure hydrocephalus||Ataxia, dementia, urinary incontinence||Ataxic gait, change in mental status||CT or MRI shows hydrocephalus|
|Dementia with Lewy bodies||Cognitive impairment, hallucinations, episodes of delirium, parkinsonism||Impaired attention and visuospatial abilities, increased falls, episodes of syncope||PET shows low glucose metabolism in cortex|
- Idiopathic Parkinson’s disease (PD)
- Parkinsonian-plus syndromes:
- Corticobasal degeneration (CBD)
- Secondary parkinsonism:
- Degenerative disorders:
- Alzheimer’s disease
- Parkinson—dementia—MND complex
- Genetic disorders:
- Wilson’s disease (consider in all cases < 50 years)
- Huntington’s disease (akinetic rigid (Westphal) variant)
- Dopa-responsive dystonia
- No diagnostic test for PD. Diagnosis is made on clinical grounds.
- Exclude Wilson’s if onset < 50 years:
- serum copper, caeruloplasmin;
- 24 hour urinary copper;
- slit lamp examination for Kayser–Fleischer rings.
- MSA patients may have degeneration of Onuf’s nucleus—detected as polyphasic potentials with ↑ latency on urethral or sphincter EMG.
- Autonomic function tests, if MSA differential. Similarly, a cognitive assessement: dementia is unusual in MSA.
|Side note DaTscan is a dopamine transporter (DAT) single photon emission computerized tomography (SPECT) imaging technique. It provides a potential tool to evaluate patients with unclear PS symptoms. It can be used to differentiate between disorders of essential tremor or drug induced PS.|
- Cardinal Signs
- Distal resting tremor
- Postural instability
- Patients must also respond to an adequate therapeutic challenge of levodopa or a dopamine agonist
- Symmetrical onset
These features are unilateral at onset, but become bilateral as the condition progresses. Later, postural instability and falls, orthostatic hypotension, decreased olfaction, micrographia and dementia.
|Side note Imaging plays a limited role in diagnosis and should not be used routinely.|
Hallmarks of PD are the presence of Lewy bodies + neuronal cell death in the pars compacta of the substantia nigra.
PD does not develop until striatal dopamine (DA) levels drop to 20% and substantia nigra (SN) cell loss exceeds 50%.
|Watch Parkinson’s Disease Pathophysiology|
- PD nurse
- Occupational therapist
- Speech therapist
- Social worker
- Levodopa (Gold Standard) + Carbidopa
- Caribidopa prevents peripheral conversion of levodopa to dopamine by blocking dopa decarboxylase.
- Carbidopa increases cerebral levodopa bioavailability and reduces the peripheral adverse effects of dopamine (e.g., nausea, hypotension)
- Dopamine Agonists (First-line of young patients)
|Remember Monitor for motor complications (dyskinesias, motor fluctuations) and impulsivity and adjust doses accordingly|
Other Pharmacological Treatment
- Anticholinergic agents
- COMT inhibitor
|Side Note Motor complications develop in 50% of all PD patients after 6 years of levodopa therapy|
|Pharmacology Levodopa Side-effects: nausea, vomiting, anorexia. Long-term complications of Levodopa: Dyskinesias, Dystonia, Unpredictable on/off switching, Confusion, Visual hallucinations, Delusions, Illusions|
|Pharmacology Dopamine Agonists directly stimulate dopamine receptors Side effect: nausea, vomiting, postural hypotension, confusion, hallucinations, somnolence|
|Remember Do not stop treatment abruptly because this may cause malignant hyperthermia (Parkinson hyperpyrexia syndrome)|
|Watch Pharmacology – anti parkinson drugs|
Deep brain stimulation of the subthalamic nucleus can improve Parkinson’s disease symptoms.
Complication and Prognosis
- Depression (50%)
- Psychosis (50%)
- Sleep Disturbance
- Excess salivation due to an inabilty to swallow
- Falls and postural instability
- Progressive decline in motor and cognitive function and increased mortality.
- Risk factors for more rapid decline in motor function include older age at diagnosis, and prominent bradykinesia and rigidity at diagnosis.
- Prominent tremor at diagnosis may predict a slower rate of disease progression
- Sixty percent of patients with Parkinson disease develop dementia within 12 years of diagnosis.
|Freezing occurs when patients are unable to move their feet when trying to walk. It affects half of all people who have Parkinson’s disease|
Essential Tremors (differential)
Overview Essential tremor is an important differential from a pill rolling parkinson tremor. Postural or kinetic tremor in the frequency range of 4 to 12 Hz (usually at the lower end of the range in older patients) is generally the only manifestation in patients with essential tremor. Occasionally, when severe, rest tremor and mild abnormalities of tone and gait may also occur. A family history of this disease and temporary benefit after drinking alcohol are common, but not invariable.
- Mild – no treatment
- Moderate – Severe
- +/- Propranolol or Primidone
- Idiopathic Parkinson’s
- Slow progression
- Good response to L-dopa
- Drug Induced
- Lower limb involvement with upper limb sparing
- Vascular Risk factor
- Akinetic rigid syndrome
Akinetic Rigid Syndromes
In patients above 40 years of age neurodegenerative disease is the commonest etiology of akinetic rigid syndrome. In this group idiopathic Parkinson’s disease (PD) needs to be differentiated from other syndromes as it carries a better prognosis. These diseases are slowly progressive and have characteristic extra pyramidal signs progression and associated neurological involvement.
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Vascular Parkinsonism
- Hereditary Causes of Akinetic Rigid Syndrome
- Hereditary Disease with Akinetic Rigid Syndrome as Minor Component
- Wilsons disease
- Huntington’s disease
- Parkinson’s disease (PD)
- Diffuse Lewy body disease
- Corticobasalganglionic degeneration (CBD)
Secondary akintetic rigid syndrome
- Infections or post infection
- Metabolic and autoimmune