Parkinson’s Disease

• Parkinson’s disease is a condition where there is a progressive reduction in dopamine in the basal ganglia, leading to disorders of movement.
• The symptoms of Parkinson’s disease are characteristically asymmetrical, with one side of the body affected more.
• The typical patient with Parkinson’s disease is an older man, around 70 years old, with a gradual onset of symptoms.
• There is a classic triad of features in Parkinson’s disease: Resting tremor, Rigidity, and Bradykinesia.
• The basal ganglia are a group of structures situated near the centre of the brain, responsible for coordinating habitual movements such as walking, controlling voluntary movements and learning specific movement patterns.
• Dopamine plays an essential role in the basal ganglia function.
• Patients with Parkinson’s disease have a slow but progressive drop in dopamine production.
• Tremor in Parkinson’s is worse on one side and has a 4-6 hertz frequency, meaning it cycles 4-6 times per second.
• Tremor in Parkinson’s is described as a “pill-rolling tremor” due to the appearance of rolling a pill between their fingertips and thumb.
• Tremor in Parkinson’s is more noticeable when resting and improves on voluntary movement.
• Tremor in Parkinson’s gets worse when the patient is distracted.
• Rigidity is the resistance to the passive movement of a joint.
• Multiple system atrophy is a rare condition where the neurones of various systems in the brain degenerate, including the basal ganglia, leading to a Parkinson’s presentation.
• Dementia with Lewy bodies is a type of dementia associated with features of Parkinsonism, causing a progressive cognitive decline.
• Performing a task with the other hand, such as miming the act of painting a fence, exaggerates the tremor.
• Parkinson’s tremor is asymmetrical, occurs at a frequency of 4-6 hertz, worsens at rest, improves with intentional movement, and is worse with intentional movement.
• Degeneration in other areas of the brain in multiple system atrophy leads to autonomic dysfunction (causing postural hypotension, constipation, abnormal sweating and sexual dysfunction) and cerebellar dysfunction (causing ataxia).
• Bradykinesia describes the movements getting slower and smaller and presents in several ways: handwriting gets smaller and smaller (micrographia), small steps when walking (“shuffling” gait), rapid frequency of steps to compensate for the small steps and avoid falling (“festinating” gait), difficulty initiating movement (e.g., going from standing still to walking), difficulty in turning around when standing and having to take lots of little steps to turn, reduced facial movements and facial expressions (hypomimia).
• Progressive supranuclear palsy and corticobasal degeneration are other Parkinson’s-plus syndromes to be aware of.
• The NICE guidelines (2017) recommend the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria for the diagnosis of Parkinson’s disease.
• Parkinson’s disease is diagnosed clinically based on the history and examination findings, and should be made by an experienced specialist.
• Other features of Parkinson’s disease include depression, sleep disturbance and insomnia, loss of the sense of smell (anosmia), postural instability (increasing the risk of falls), cognitive impairment and memory problems.
• Patients may describe themselves as “on” when the medications are acting, and they are moving freely, and “off” when the medications wear out, they are experiencing symptoms and their next dose is due.
• Treatment for Parkinson’s disease is initiated and guided by a specialist, tailored to each individual and their response to different medications, with no cure, and focused on controlling symptoms and minimising side effects.
• Taking a hand and passively flexing and extending the arm at the elbow demonstrates tension in the arm that gives way to movement in small increments, like little jerks, which is described as “cogwheel” rigidity.
• Pulmonary fibrosis is a notable side effect with prolonged use of dopamine agonists.
• Monoamine oxidase-B inhibitors block the action of monoamine oxidase-B enzymes, helping to increase the circulating dopamine.
• Monoamine oxidase-B inhibitors are typically used to delay the use of levodopa, then in combination with levodopa to reduce the “end of dose” worsening of symptoms.
• COMT Inhibitors, such as entacapone, are inhibitors of catechol-o-methyltransferase (COMT), which metabolises levodopa in both the body and brain.
• Levodopa is the most effective treatment for symptoms but becomes less effective over time.
• Examples of monoamine oxidase-B inhibitors include Selegiline, Rasagiline.
• Examples of dopamine agonists include Bromocriptine, Pergolide, and Cabergoline.
• Combination drugs include Co-beneldopa (levodopa and benserazide), with the trade name Madopa, and Co-careldopa (levodopa and carbidopa), with the trade name Sinemet.
• Levodopa is often reserved for when other treatments are not controlling symptoms.
• Dopamine agonists are less effective than levodopa in reducing symptoms and are typically used to delay the use of levodopa, then used in combination with levodopa to reduce the required dose.
• Monoamine oxidase-B is more specific to dopamine.
• The main side effect of levodopa is dyskinesia, which refers to abnormal movements associated with excessive motor activity.
• Examples of dyskinesia include Dystonia, Chorea, Athetosis, and Amantadine is a glutamate antagonist that may be used to manage dyskinesia associated with levodopa.
• Dopamine agonists mimic the action of dopamine in the basal ganglia, stimulating the dopamine receptors.
• Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow the breakdown of the levodopa in the brain, extending the effective duration of the levodopa.