Neurology
Question 110 of 180
A 65 year old man presents to the Emergency Department following a fall. On examination you note he has a resting tremor, rigidity, bradykinesia and a shuffling gait. You suspect he has Parkinson's disease. Parkinson's disease results from which of the following mechanisms?
Answer:
Parkinson's disease is a chronic, progressive neurodegenerative condition resulting from the loss of the dopamine-containing cells of the substantia nigra. The resulting dopamine deficiency within the basal ganglia leads to a movement disorder with classical parkinsonian motor symptoms. Parkinson's disease is not clinically apparent until at least 50% of dopaminergic cell activity has been lost.Parkinson's Disease
Neurology
Last Updated: 12th February 2021
Parkinsonism is an umbrella term for the clinical syndrome involving bradykinesia plus at least one of tremor, rigidity, and/or postural instability.
- Parkinson's disease is the most common form of parkinsonism.
- Other causes of parkinsonism include drug-induced parkinsonism, cerebrovascular disease, Lewy body dementia, multiple system atrophy, and progressive supranuclear palsy.
Pathophysiology
Parkinson's disease is a chronic, progressive neurodegenerative condition resulting from the loss of the dopamine-containing cells of the substantia nigra. The resulting dopamine deficiency within the basal ganglia leads to a movement disorder with classical parkinsonian motor symptoms. Parkinson's disease is not clinically apparent until at least 50% of dopaminergic cell activity has been lost.
The exact cause of Parkinson's disease remains unknown, and it seems to result from a complex interplay of genetic and environmental factors. The majority of cases are thought to arise sporadically, although up to 20% of people with Parkinson's disease have a family history of Parkinson's disease in a first-degree relative.
Clinical features
Suspect Parkinson's disease if a person has progressive:
- Bradykinesia (slowness in initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive actions, such as finger or foot tapping) or
- Hypokinesia (poverty of movement) — for example:
- Reduced facial expression, arm swing, or blinking.
- Difficulty with fine movements such as buttoning clothes and opening jars, or small, cramped handwriting (micrographia).
- Slow, shuffling, festinating gait, or difficulty turning in bed.
In addition, the person typically presents with at least one of the following:
- Stiffness or rigidity predominantly affecting the side of onset, which may be:
- Lead-pipe rigidity, which describes the constant resistance felt when a limb is passively flexed in the presence of increased tone without tremor, or
- Cogwheel rigidity, which describes the regular intermittent relaxation of tension felt when a limb is passively flexed in the presence of tremor and increased tone.
- Resting tremor, which:
- Usually improves on moving, with mental concentration, and during sleep.
- May affect the thumb and index finger ('pill-rolling'), the wrist, or the leg. It may also affect the lips, chin, and jaw, but rarely involves the head, neck, or voice.
- Is absent in up to 30% of people at disease onset.
- Balance problems and/or gait disorders.
- Postural instability is suggested by the 'pull test' — a tendency 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.
Differential diagnosis
Other causes of parkinsonism include:
- Drug-induced parkinsonism
- Possible causative drugs include:
- Antipsychotics (parkinsonism symptoms usually appear within 10 weeks of starting the drug):
- Antiemetics e.g. prochlorperazine, metoclopramide
- Other drugs (more rarely) e.g. antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), calcium-channel blockers, cinnarizine, amiodarone, lithium, cholinesterase inhibitors, such as donepezil or memantine, sodium valproate, methyldopa, pethidine
- Cerebrovascular disease
- Non-Parkinson's dementia (including dementia with Lewy bodies and Alzheimer's disease).
- Other neurodegenerative parkinsonian syndromes, which involve a wider area of the nervous system than idiopathic Parkinson's disease, such as:
- 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
- Repeated head injury
Other causes of tremor include:
- Postural and action tremor
- Essential tremor (Essential tremor is common; onset is at any age, and often there is a family history. Typically tremor is bilateral and symmetrical; may worsen with stress, caffeine, sleep deprivation; typically involves the head, neck, or voice as well as the limbs; and often improves with alcohol and beta-blockers.)
- Exaggerated physiological tremor
- Dystonic tremor
- Hyperthyroidism
- Drugs, such as beta-2 agonists
- Intention tremor
- Cerebellar disorders
Diagnosis and management
- Refer all people with suspected Parkinson's disease urgently, and untreated, to a specialist with appropriate expertise in movement disorders (such as a neurologist or elderly care physician), for confirmation of the diagnosis and exclusion of alternative diagnoses. The diagnosis is almost entirely based on clinical examination.
- Ensure that any person with confirmed Parkinson's disease is under the care of a specialist in movement disorders and a multidisciplinary team including a Parkinson's disease nurse specialist, who can advise on management issues and provide ongoing support.
- Specialist management of motor symptoms or complications of Parkinson's disease may include the following drugs, depending on the person's symptoms and wishes, comorbidities, risks from polypharmacy, and potential benefits and harms of the different drug classes:
- First-line treatments
- Levodopa, which is usually given with a dopa decarboxylase inhibitor, as co-beneldopa or co-careldopa
- Levodopa is usually offered to people in the early stages of Parkinson's disease whose motor symptoms impact on their quality of life.
- Levodopa typically provides more improvement in motor symptoms and daily functioning, fewer adverse effects such as excessive sleepiness, hallucinations, and impulse control disorders, but may cause more motor complications than other drug classes.
- Oral monoamine oxidase-B (MAO-B) inhibitors (selegiline, rasagiline, or safinamide)
- These typically provide less improvement in motor symptoms and daily functioning, fewer motor complications, and fewer adverse effects such as excessive sleepiness, hallucinations, and impulse control disorders than other drug classes.
- Oral dopamine agonists, such as pramipexole or ropinirole; or transdermal dopamine agonist, such as rotigotine
- These typically provide less improvement in motor symptoms and daily functioning, fewer motor complications, but more adverse effects such as excessive sleepiness, hallucinations, and impulse control disorders than other drug classes.
- Levodopa, which is usually given with a dopa decarboxylase inhibitor, as co-beneldopa or co-careldopa
- Adjuvant treatment
- Oral catechol-O-methyl transferase (COMT) inhibitors (such as entacapone)
- These may be used as an adjunct to levodopa for people who have developed dyskinesia or motor fluctuations despite optimal levodopa therapy.
- Oral amantadine
- This may be considered if dyskinesia is not adequately managed by modifying existing antiparkinsonian therapy.
- Subcutaneous apomorphine (dopamine agonist)
- This may be offered to people with advanced Parkinson's disease on optimal oral treatment, as intermittent subcutaneous bolus injections and/or continuous subcutaneous infusion.
- Deep brain stimulation (DBS) of the subthalamic nucleus
- This may be considered for people with advanced Parkinson's disease with motor complications refractory to optimal medical treatment who are fit, levodopa-responsive, and have no comorbid mental health conditions.
- Oral catechol-O-methyl transferase (COMT) inhibitors (such as entacapone)
- First-line treatments
Complications
- Motor complications
- Deteriorating function
- Loss of drug effect
- Motor fluctuations
- Dyskinesia
- Freezing of gait
- Falls
- Non-motor complications
- Mental health conditions:
- Depression, anxiety, and apathy
- Dementia and cognitive impairment
- Impulse control disorders and psychotic symptoms (delusions and hallucinations)
- Autonomic dysfunction:
- Constipation
- Orthostatic hypotension
- Dysphagia and weight loss
- Excessive salivation and sweating
- Bladder and sexual problems
- Other complications:
- Nausea and vomiting
- Pain
- Sleep disturbance and daytime sleepiness
- Aspiration pneumonia
- Pressure sores
- Mental health conditions:
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
