Parkinsons disease

Question 1

Describe the pathophysiology of Parkinson’s disease including the characteristic pathological features and the degeneration of specific neuronal populations.

Answer 1

Parkinson’s disease is characterized by neuronal loss in pigmented brainstem nuclei, presence of Lewy bodies with abnormal α-synuclein aggregates, and progressive loss of dopaminergic neurons in the pars compacta. Additionally, there is degeneration of cholinergic neurons in the pedunclopontine nucleus, GABA-containing neurons in the striatum, and noradrenergic/serotonergic neurons in the locus coeruleus and raphé nucleus.

Question 2

How do motor symptoms manifest in Parkinson’s disease, and what are the key features of bradykinesia?

Answer 2

Motor symptoms in Parkinson’s disease include bradykinesia, resting tremor, extrapyramidal rigidity, and postural instability. Bradykinesia is characterized by slowness in initiating voluntary movements, progressive reduction in speed and amplitude of actions, reduced facial expression, arm swing, blinking, fine movements, and micrographia.

Question 3

Define Parkinsonism and differentiate it from Parkinson’s disease. What are the clinical features of Parkinsonism?

Answer 3

Parkinsonism is a clinical syndrome characterized by bradykinesia along with at least one of tremor, rigidity, or postural instability. Parkinson’s disease is the most common form of Parkinsonism. Clinical features include bradykinesia, tremor, rigidity, and postural instability.

Question 4

Describe the prognosis of Parkinson’s disease, including the progression, complications, and factors influencing outcomes.

Answer 4

Parkinson’s disease progresses slowly but variably, leading to a range of motor and non-motor complications. Factors such as older age at onset, longer disease duration, and higher prevalence of complications can impact prognosis. Life expectancy decreases, with higher mortality rates and increased risk of dementia.

Question 5

What are Lewy bodies in the context of Parkinson’s disease, and how do they contribute to the pathology of the condition?

Answer 5

Lewy bodies are protein aggregates of abnormal α-synuclein found in surviving cells in Parkinson’s disease. They are not specific for PD but are a characteristic feature. The presence of Lewy bodies contributes to neuronal death, particularly in the substantia nigra, exacerbating the loss of dopaminergic neurons.

Question 6

Describe the impact of Parkinson’s disease on specific neuronal populations such as cholinergic, GABAergic, noradrenergic, and serotonergic neurons.

Answer 6

Parkinson’s disease leads to degeneration of cholinergic neurons in the pedunclopontine nucleus, GABAergic neurons in the striatum, and noradrenergic/serotonergic neurons in the locus coeruleus and raphé nucleus. This degeneration contributes to various symptoms such as postural instability, dysphagia, dyskinesias, and depression.

Question 7

Describe the characteristics of resting tremor in Parkinson’s disease.

Answer 7

Resting tremor in Parkinson’s disease is a rhyth movement with a frequency of 4-6 Hz that usually improves on moving, with mental concentration, and during sleep. It may affect thumb and index finger (‘pill-rolling’), wrist, or leg, but rarely involves the head, neck, or voice. It can be absent in up to 30% of people at disease onset.

Question 8

What are the features of extrapyramidal rigidity in Parkinson’s disease?

Answer 8

Extrapyidal rigidity in Parkinson’s disease is due to increased muscle tone and predominantly affects the side of onset. It can present as lead pipe rigidity, which is constant resistance felt when a limb is passively flexed, or cogwheel rigidity, which is regular intermittent relaxation of tension felt during passive flexion.

Question 9

How does postural instability manifest in Parkinson’s disease?

Answer 9

Postural instability in Parkinson’s disease is a late feature characterized by a tendency to be unstable when standing due to impaired reflexes necessary for maintaining an upright position. Patients may experience difficulty when rising from bed or chair, turning, or pivoting, leading to an increased risk of falls.

Question 10

Describe the features of festinating gait in Parkinson’s disease.

Answer 10

Festinating gait in Parkinson’s disease is characterized by an abnormal stooped posture, progressive increase in speed, and shortening of step. Patients take multiple short steps to catch up with the center of gravity and avoid falling. Turning and changing direction become difficult.

Question 11

What are some common non-motor symptoms associated with Parkinson’s disease?

Answer 11

Non-motor symptoms in Parkinson’s disease include autonomic dysfunction (drooling, seborrhea, urogenital difficulties), depression, anxiety, fatigue, cognitive impairment, psychosis, sleep disturbance, and orthostatic hypotension.

Question 12

Discuss the differential diagnosis of Parkinson’s disease.

Answer 12

The ‘All that shakes is not Parkinson’s disease’ concept highlights other causes of parkinsonism, such as drug-induced parkinsonism, cerebrovascular disease, non-Parkinson’s dementia, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, repeated head injury, and essential tremor.

Question 13

Describe the characteristics of drug-induced parkinsonism, including its reversibility, common demographics, motor symptoms, and the impact of withdrawing the offending drug.

Answer 13

Drug-induced parkinsonism is potentially reversible upon stopping the causative drug. It is more common in the elderly and women. Motor symptoms are rapid in onset, bilateral, and may present as action tremor without rigidity or resting tremor. Withdrawal of the offending agent leads to improvement in about 80% of cases, although full resolution may take up to 18 months.

Question 14

How is drug-induced parkinsonism diagnosed, and what are the challenges associated with its diagnosis?

Answer 14

Diagnosing drug-induced parkinsonism can be challenging. General practitioners encounter one new case of Parkinson’s disease approximately every 3.3 years. Diagnosis requires the presence of bradykinesia and tremor at rest, rigidity, or postural instability, along with the absence of secondary causes like drugs or metabolic issues. Definitive diagnosis usually only occurs post-mortem.

Question 15

Define the Hoehn and Yahr scale in Parkinson’s disease management, outlining the different stages and their descriptions.

Answer 15

The Hoehn and Yahr scale categorizes Parkinson’s disease progression into stages. Stage 1 involves unilateral involvement with minimal functional disability, while stage 5 signifies confinement to bed or wheelchair. The scale helps clinicians assess disease severity and progression.

Question 16

What are the initial treatment options for early Parkinson’s disease management, and when might therapy with multiple antiparkinsonian drugs be necessary?

Answer 16

Initial treatment for early Parkinson’s disease includes levodopa, dopamine-receptor agonists, and monoamine-oxidase-B inhibitors. As the disease progresses, therapy with two or more antiparkinsonian drugs may be required. Most patients eventually need levodopa and may develop motor complications.

Question 17

Describe the common drugs that can induce parkinsonism, including antipsychotics, antiemetics, antidepressants, and others, and explain their role in causing this condition.

Answer 17

Various drugs can induce parkinsonism, including antipsychotics (especially 1st generation), antiemetics like prochlorperazine and metoclopramide, antidepressants such as SSRIs, and others like Ca2+ channel blockers, amiodarone, lithium, cholinesterase inhibitors, sodium valproate, methyldopa, and pethidine. These medications can lead to the development of parkinsonian symptoms.

Question 18

Describe the first-line treatments for managing motor symptoms in Parkinson’s disease.

Answer 18

The first-line for managing motor symptoms in Parkinson’s disease include Levodopa dopa decarboxylase inhibitor, oral monoamine oxidase-B (MAO-B) inhibitors, oral agonists, oral catechol-O-methyl transferase (COMT) inhibitors oral amantadine, and subcutaneous apomorphine.

Question 19

How does Levodopa work in the management of Parkinson’s disease?

Answer 19

Levodopa by replenishing depleted striatal dopamine. It is given with an extracerebral dopa-decarboxylase inhibitor to limit peripheral conversion of levodopa to dopamine, reducing side effects like nausea and vomiting. It is effective and well tolerated in the majority of patients.

Question 20

Define the concept of response fluctuations in Parkinson’s disease treatment with Levodopa.

Answer 20

Response fluctuations in Parkinson’s disease treatment with Levodopa refer to the alternating periods of normal function (‘on’ period) and weakness/restricted mobility (‘off’ period). This can also include ‘end-of-dose’ deterioration. Modified-release preparations may help manage these fluctuations.

Question 21

Describe the role of Monoamine-oxidase-B (MAO-B) inhibitors in Parkinson’s disease treatment.

Answer 21

MAO-B inhibitors like rasagiline and selegiline hydrochloride slow down the breakdown of dopamine in the striatum, leading to a ‘Levodopa sparing’ effect. They may delay the onset of motor complications and have fewer adverse effects compared to other drug classes. They do not interact with tyramine-rich foods.

Question 22

How do dopamine agonists work in the treatment of Parkinson’s disease?

Answer 22

Dopamine agonists act directly on dopamine receptors. They are often used as initial treatment, with drugs like pramipexole, ropinirole, and rotigotine. They have fewer motor complications in long-term use compared to levodopa but are associated with more psychiatric side effects. S/C apomorphine hydrochloride is used in advanced disease for unpredictable ‘off’ periods.

Question 23

Describe the potential side effects associated with dopamine agonists in Parkinson’s disease treatment.

Answer 23

Dopamine agonists in Parkinson’s disease treatment can lead to side effects such as ‘sleep attacks’ with sudden drowsiness, excessive daytime somnolence, and impulse control disorders like pathological gambling, hypersexuality, and excessive shopping. Patients should be advised about these risks, especially regarding driving.

Question 24

Describe the use of Catechol-O-methyl transferase (COMT) Tolcapone and Entacapone, including their differences and monitoring requirements.

Answer 24

Catechol-O-methyl transferase (COMT) inhibitorscapone and Entacapone are used in Parkinson’s disease. Tolcapone was suspended due to hepatotoxicity fears but reintroduced with strict monitoring. Entacapone does not affect liver function and helps reduce ‘off’ time. Tolcapone is used after Entacapone, with liver function tests monitored biweekly for the first year.

Question 25

What are the characteristics and uses of antimuscarinic drugs in Parkinson’s disease treatment, and how do they differ from dopaminergic drugs?

Answer 25

Antimuscarinic drugs are useful in drug-induced parkinsonism but not idiopathic PD. They are less effective than dopaminergic drugs and can increase neuropsychiatric and cognitive adverse events. Drugs like Orphenadrine, procyclidine, and trihexyphenidyl can alleviate symptoms induced by antipsychotic drugs, but they do not improve tardive dyskinesia.

Question 26

How do motor complications manifest in Parkinson’s disease, and what are the different types of motor fluctuations observed?

Answer 26

Motor complications in Parkinson’s disease include deteriorating function, motor fluctuations like end-of-dose fading, on-off phenomenon, and dyskinesia (choreiform, dystonic). Other manifestations include freezing of gait, falls, and neuroleptic malignant syndrome.

Question 27

Describe the management strategies for non-motor symptoms like constipation, nausea, vomiting, sleep disturbance, depression, and orthostatic hypotension in Parkinson’s disease.

Answer 27

Management of non-motor symptoms in Parkinson’s disease involves a stepped approach for constipation, avoiding metoclopramide or prochlorperazine for nausea/vomiting, addressing sleep hygiene for sleep disturbances, being cautious with SSRIs for depression, and stopping contributing medications for orthostatic hypotension.

Question 28

How should healthcare providers address issues like vitamin D supplementation, driving, medication review, co-morbidities, and support for patients and carers in Parkinson’s disease management?

Answer 28

In Parkinson’s disease management, healthcare providers should consider vitamin D supplementation, assess driving safety, conduct regular medication reviews, manage co-morbidities, and provide additional support for patients and carers through referral to multidisciplinary teams and other sources of support.

Question 29

Explain the reasons behind the suspension and reintroduction of Tolcapone in Europe for Parkinson’s disease treatment, highlighting the precautions taken upon its reavailability.

Answer 29

Tolcapone, a Catechol-O-methyl transferase (COMT) inhibitor, was initially suspended in Europe due to hepatotoxicity concerns. It was reintroduced in 2005 with strict prescribing and monitoring requirements, including the need to use it only after Entacapone, and regular liver function tests every two weeks for the first year.