Armando Hasudungan
Biology and Medicine videos

Parkinson’s Disease

 

 

Overview

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
Definition
Parkinson’s Disease: or Idiopathic Parkinson’s disease is a  progressive, degenerative brain disease that causes trembling, stiffness, slowness of movement and a loss of fine motor control. It is the most common type of parkinsonism. Unlike some other forms which have specific causes it is not known why idiopathic Parkinson’s occurs.
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.
Parkinson’s – Plus Syndrome: neurodegenerative conditions with Parkinson’s characteristics but with additional features that distinguish them from idiopathic Parkinson’s disease. Usually they are not responsive to dopamine.

Risk Factors

↑Risk ↓Risk
Pesticides Smoking
Rural residence Caffiene
Farming
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)

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
Remember Rapid eye movement (REM) sleep behavior disorder a prodromal syndrome of alpha-synuclein neurodegeneration including parkinsnon’s disease and some parkinson’s plus syndrome. REM sleep behaviour disorder is characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia.

4 cardinal motor symptoms (more info below)

  • Resting Tremor
  • Bradykinesia
  • Rigidity
  • Postural instability (late finding)

Resting Tremor

  • Pill-rolling
  • Disappears with voluntary movement and sleep
  • 30% no tremor at onset (Most develop as disease progresses)
  • asymmetrical

Bradykinesia

  • 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

Postural instability

  • 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

Differential Diagnosis

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 Parkinson’s Disease.
  • 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’).
CAUSES OF PARKINSONISM
Condition History Signs and symptoms Radiological findings
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
Parkinson’s Plus syndrome
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

Normal Voluntary Motor Pathway

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Aetiology of Parkinsonism

  • Idiopathic Parkinson’s disease (PD)
  • Parkinsonian-plus syndromes:
    • Progressive supranuclear palsy
    • Multisystem atrophy (MSA)
    • Corticobasal degeneration (CBD)
  • Secondary parkinsonism:
    • Vascular
    • Drug-induced
    • Post-encephalitic
    • Hydrocephalus
  • 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
Remember Drug-induced parkinsonism is symmetric, lacks nonmotor features, and is reversible after removal of the causative agent. Typical antipsychotics, also known as neuroleptics, are the most common causes of DIP

 

Investigations

Investigations

  • No diagnostic test for Parkinson’s Disease. Diagnosis is made on clinical grounds.
  • Brain imaging is recommended to rule out vascular disease and hydrocephalus.
  • A dopamine transporter scan (DaTscan) – can be used as a confirmatory test.
    • The test cannot distinguish between Parkinson disease and Parkinson-plus conditions.
  • Exclude Wilson’s if onset < 50 years:
    • serum copper, caeruloplasmin;
    • 24 hour urinary copper;
    • slit lamp examination for Kayser–Fleischer rings.
  • MRI Brain/ CT Brain
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.

Diagnosis

Clinical Diagnosis

  • Cardinal Signs
    • Distal resting tremor
    • Rigidity
    • Bradykinesia
    • 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 (Lewy bode dementia)

Side note Imaging plays a limited role in diagnosis and should not be used routinely.

Pathophysiology

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%.

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Flow Diagram of the Pathophysiology of Parkinsons

 


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Watch Parkinson’s Disease Pathophysiology

Management

  • Treatment is symptomatic and does not prevent progression of disease.
  • About 50% of patients develop levodopa related complications- motor fluctuations about 5-10 years after starting therapy on dopamine replacement therapy
  • While medications improve motor and non-motor symptoms, they do not improve balance

Multidisciplinary team 

  • Physician
  • PD nurse
  • Physiotherapist
  • Occupational therapist
  • Speech therapist
  • Social worker

Pharmacological Treatment

  • 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)
  • MOAB Inhibitors – for mild symptoms can be firstl
  • Apomorphine
Remember Monitor for motor complications (dyskinesias, motor fluctuations) and impulsivity and adjust doses accordingly
Remember For Parkinson’s disease who have new troublesome hallucinations or delusions, a precipitant such as an underlying delirium, infection or dementia should be ruled out. Then, if able, anti-Parkinsonian medications should be adjusted. If despite this the delusions continue, then options include treatment with quetiapine, clozapine, or pimavanserin. Other antipsychotics will worsen Parkinsonian symptoms.

Other Pharmacological Treatment

  • Anticholinergic agents
  • Amantidine
  • 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 and impulsivity, somnolence
Remember Do not stop treatment abruptly because this may cause neuroleptic malignant syndrome, which is then treated with dantrolene and bromocriptine (dopamine agonist)

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Watch Pharmacology – anti parkinson drugs

Surgical Treatment

  • Deep brain stimulation –  Surgical procedure that involves placing of probes into the Subthalamic Nucleus (STN) or internal Globus Pallidus (GPi) and has a neurostimulator which sends electrical impulses to specific nuclei.
  • Duodopa – Continous Levodopa Carbidopa Intestinal Gel Infusion  through a percutaneous gastrojejunostomy tube by an externally carried pump.

Complication and Prognosis

Complications 

  • Depression (50%)
  • Psychosis (50%)
  • Dementia
  • Sleep Disturbance
  • Excess salivation due to an inabilty to swallow
  • Falls and postural instability
  • Freezing
  • Medication complications
    • Neuroleptic malignant syndrome (when dopamine is stopped suddenly)
    • Serotonin syndrome (cause by MOAI)
Neuroleptic malignant syndrome should be considered in patients taking antipsychotic medications (dopamine antagonist) or for those who stop taking dopamine replacement medications suddenly. Clinical manifestation include fever, rigidity, altered mental statu, autonomic dysfunction (hypersalvation, urinary incontinence), and elevated creatine phosphokinase concentration

Prognosis

  • 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.

Management

  • Mild – no treatment
  • Moderate – Severe
    • +/- Propranolol or Primidone