Parkinson’s disease E-book Flashcards
PDs is characterised by
low dopamine levels and a loss of dopamine neurons in the substantia nigra meaning a loss of neuronal transmission through the nigrostriatal pathway. Concurrently, there is an accumulation of Lewy body proteins in these neurons.
Other forms of PD:
- Drug-induced parkinsonism (See differential Diagnosis)
- Secondary to encephalitis (degeneration of dopamine-containing nigrostriatal fibres)
- Toxins (manganese and carbon monoxide poisoning)
- Other progressive brain conditions (Wilson’s Disease)
- Cerebrovascular disease - where a number of mini-strokes cause brain death in certain areas.
Clinical Features
Stage 1- Mild
• Unilateral tremor
• Rigidity and stiffness
• Poor co-ordination and lack of control and stability in one leg
• One side of the face becomes less animated impacting expression
• Symptoms are not overly noticeable to those around patients
Stage 2- Mild
• Bilateral tremor
• Worsened rigidity and stiffness
• Gait disorders and stooping become more noticeable
• Everyday activities become more difficult
Stage 3- Moderate
• Motor symptoms become more severe- tremor, dyskinesia, dystonia
• Balance and gait are significantly affected
• Hyperkinesia and bradykinesia
• Increased risk of falls
Stage 4- Severe
• Patients can still stand without assistance but a noticeable incapacitated
• Can’t undertake activities of daily living
• Severe loss dexterity
• Cannot live independently
Stage 5- Severe • Freezing of gait • Hallucinations and delusions • Cognitive impairment • High risk of falls • May require a wheelchair
Mental Health Problems associated with PD:
Depression Anxiety Apathy Dementia Delusions and Hallucinations
Autonomic dysfunction symptoms caused by PD
Orthostatic hypotension
Bladder dysfunction and urinary incontinence
Excessive salivation from oropharyngeal dysfunction and dysphagia
Dysphagia
Sexual problems
Excessive sweating
Constipation
Other complication caused by PD
Pain
Sleep Disturbance
Daytime Sleepiness
The following table outlines the side effects relating to the use of anti-parkinsonian medicines and their ‘onoff’ effects:
Dyskinesia Choreiform (fidgety movement) Freezing of gait Dystonic ⅔ patients experience falls Neuroleptic Malignant Syndrome Impulse control disorders Dopamine dysregulation syndrome Nausea and Vomiting
There are 3 main steps in the diagnosis of Parkinson’s disease recommended by the UK Parkinson’s disease
Society
Step 1 - Diagnosis of a Parkinsonian syndrome based on certain symptoms
Bradykinesia and at least one of the following:
• Muscular rigidity
• Resting tremor (4–6Hz)
• Postural instability unrelated to primary visual, cerebellar, vestibular or proprioceptive dysfunction
Step 2 - Does the patient meet any exclusion criteria for PD?
• Repeated strokes with stepwise progression of Parkinsonian features
• Repeated head injury
• Antipsychotic or other dopamine depleting drugs
• Encephalitis or oculogyric crisis without drug treatment
• Greater than one affected relative
• Sustained remission
• Negative response to high dose levodopa (excluding malabsorption)
• Only unilateral features after three years
• Neurological features: supranuclear gaze palsy,
cerebellar signs, early severe autonomic involvement, early severe dementia
• Neurotoxin exposure
• Cerebral tumour or communicating hydrocephalus on neuroimaging
Step 3 - Does the patient meets the supportive criteria for PD.
Three or more are required for a definite diagnosis:
• Unilateral onset
• Resting tremor present
• Progressive disorder
• Persistent asymmetry affecting the side of onset most
• Excellent response to levodopa
• Severe levodopainduced chorea (involuntary jerky movement of shoulder face and hips)
• Levodopa response for over five years
• Clinical course of over 10 years
The following tests can be used to aid diagnosis, but are not always necessary:
‘Levodopa Challenge’
-Symptom improvement in response to levodopa is characteristic of Parkinson’s therefore administration of single doses has been suggested as a diagnostic test. This is not a recommended diagnostic tool due to bias/ placebo effects and other conditions may respond to Levodopa as well.
‘Pull Test’
- An indicator of postural instability testing the tendency of a patient to fall backwards after a sharp pull from the examiner. This may be suggestive of Parkinson’s disease if unrelated to primary visual, cerebellar, vestibular, or proprioceptive dysfunction.
Single photon emission computed tomography (SPECT) imaging
-measures the uptake of radiolabelled tracers that bind to the dopamine transporter protein (DAT) in nigrostriatal nerve endings. Result would be abnormal for Parkinson’s patients, in multisystem atrophy or progressive supranuclear palsy, but essential tremor and drug-induced Parkinsonism would show a normal DAT result.
‘Genetics’
-Genes associated with Parkinson’s have been identified, but monogenic forms of the disease are rare. However genetic testing is useful for patients with young-onset disease and a positive family history
Approximately 7% of patients with parkinsonism have developed their symptoms following treatment of
particular medications or dopamine receptor-blocking medication
- Amiodarone, used to treat heart problems can cause tremor,
- Anti-emetics-metoclopramide and prochlorperazine
- Cinnarizine, a calcium channel blocker used to treat hypertension, angina, depression and more, is also reported to induce Parkinson’s-esque symptoms
- Lithium and Sodium Valproate, both used to treat depression, can also cause tremor which can be mistaken for PD.
- Antipsychotics particularly first generation (e.g. haloperidol, chlorpromazine, flupentixol) although this can occur with second generation but is less common (e.g. clozapine, quetiapine, olanzapine) -symptoms usually appear within 10 weeks of starting drug.
Other medical conditions that have similar symptoms
- Cerebrovascular disease- such as repeated strokes with stepwise progression
- Non-Parkinson’s dementia (including dementia with Lewy bodies and Alzheimer’s disease).
- Progressive supranuclear palsy (suggested by early dysphagia, gaze palsy, or recurrent falls)
- Multiple system atrophy (suggested by severe early autonomic involvement such as postural hypotension, or cerebellar ataxia).
- Corticobasal degeneration (suggested by asymmetric rigidity and dystonia, with apraxia and cognitive impairment
- Wilson’s disease (suggested by Kayser-Fleischer rings caused by deposition of copper in the membrane of the cornea; variable neurological signs including tremor, ataxia, and dystonia; and non-specific liver disease).
- Essential tremor- can be differentiated by a writing test where text will become progressively larger with ET patients but smaller with PD patients
Symptoms of neuroleptic syndrome:
• Hyperthermia • Muscle rigidity • Five of the following: o Changed mental status o Tachycardia o Hypo/hypertension o Tremor o Incontinence o Diaphoresis or sialorrhoea o Increased creatinine phosphokinase or urinary myoglobin o Metabolic acidosis o Leukocytosis
what is the first line treatment for patients in the early stages of Parkinson’s disease whose symptoms are beginning to affect their quality of life.
levodopa
If the patient is experiencing symptoms, but they do not impact their quality of life significantly, alternatives are
dopamine agonists or monoamine oxidase B
(MAO-B) inhibitors.
Pharmacological Neuroprotective therapies that are not recommended by NICE:
- Vitamin E
- Co-enzyme Q10
- Dopamine Agonists
- MAO-B inhibitors
