Neuro - Parkinson's Disease, Parkinsonism and Huntington’s disease Flashcards

1
Q

List some causes of Parkinsonism

A

-Medications: dopamine antagonists (haloperidol), lithium
-Trauma: subdural haematoma, repetitive brain injury
-Cerebrovascular disease: lacunar infarcts in basal ganglia and small vessel disease of cerebral white matter
-Hydrocephalus or tumour
Infections: encephalitis lethargica and Japanese B encephalitis
-Atypical parkinsonian disorders: MSA, PSP and corticobasal degeneration
-Wilson’s disease: high serum copper can cause copper deposits in basal ganglia - pts present in teens/early adult life with atypical Parkinsonism, tremor, dystonia, cerebellar signs and cognitive decline/psychiatric sx

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2
Q

What is MSA?

A
  • Multiple system Atrophy - rare condition with neurones of multiple systems in the brain degenerate (affects basal ganglia and other areas) - leads to a PD presentation
  • There are two types, MSA P (predominantly parkinsonian features) and MSA C (predominantly cerebellar features)
  • Onset at around 57 years
  • Degeneration in other areas leads to autonomic dysfunction (postural hypotension, constipation, abnormal sweating, erectile dysfunction and cerebellar dysfunction (ataxia)
  • No cognitive decline
  • ‘’Hot cross bun sign’’ on MRI shows degeneration of the middle cerebllar peduncle
  • Does not respond to L-Dopa
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3
Q

What is corticobasal degeneration?

A
  • Rare disorder characterised by unilateral involvement with rigidity and dystonia in an arm.
  • No tremor but other parkinsonian sx and signs are present + cognitive and visual spatial neglect, limb apraxia (can’t make purposeful movements) and myoclonus of affected arm
  • Dysphasia and dysphagia may occur
  • Affected arm may eventually become functionally useless followed by other side becoming affected - patients eventually become bed bound through immobility and die within 6-8 years
  • L-Dopa has no effect
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4
Q

What is PSP?

A
  • Progressive supranuclear palsy
  • Mean onset is 63 years and survival is approximately 7 years

Signs:

  • Early falls
  • Symmetrical Parkinsonism and supranuclear palsy (cannot look down initially, eventually might affect all eye movements , disarthria, dysphagia) -Cognitive decline
  • think of this diagnosis in patients who do not respond to levodopa treatment and who present with recurrent falls
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5
Q

What is PD? Describe the pathophysiology

A
  • Condition where there is progressive reduction of dopamine in the basal ganglia of the brain - leads to disorders of movement
  • Pathophysiology: loss of dopaminergic neurones in substantia nigra leads to decreased dopamine (loss of stimulation of direct pathway and loss of inhibition of indirect pathway).
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6
Q

What are the three key features of PD? Name other possible features

A

Key features

  • Unilateral tremor: frequency of 4-6 Hz, pill rolling, more pronounced when resting and improved on voluntary movement, worsened when pt is distracted
  • Cogwheel rigidity: resistance to passive movement of a joint where the tension gives way to movement in small increments/jerks
  • Bradykinesia: smaller and slower movements leads to micrographia, shuffling gait, difficulty initiating movement, difficulty turning around when standing, hypomimia (reduced facial movements)

Other features:

  • Depression and or psychosis
  • Sleep disturbances and insomnia
  • Anosmia
  • Postural instability
  • Cognitive impairment and memory problems
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7
Q

What investigations should you perform on a patient with suspected PD?

A
  • Bloods: TFT, B12, LFT, serum ceroloplasmin (Wilson’s disease)
  • MRI: but may be normal in uncomplicated PD
  • DAT CT: may show decreased dopamine transporter binding in the basal ganglia but cannot distinguish between MSA, PD and PDP - should not be used routinely to confirm a diagnosis of PD
  • Diagnosis is mainly clinical
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8
Q

Name some treatments available for PD

A
  • Levodopa
  • COMT inhibitors
  • Dopamine agonists
  • MOA-B inhibitors
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9
Q

Treatment: synthetic dopamine MOA and SEs

A
  • PO synthetic dopamine is given to boost own dopamine levels and is combined with drug that inhibits peripheral breakdown of dopamine before it crosses the BBB (eg carbidopa or benserazide)
  • Examples: co-benyldopa or co-careldopa
  • Most effective treatment of sx but becomes less effective over time - reserved for when other tx are not managing to control sx.

SEs: usually caused by excessive dopamine doses - causes dyskinesia (abnormal movements associated with excessive motor activity) such as: -Dystonia: excessive muscle contraction

  • Chorea: abnormal involuntary movements
  • Athetosis: involuntary twisting or writhing movements of fingers, hand and feet
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10
Q

Treatment: COMT inhibitors MOA

A
  • Inhibitors of catechol-o-methyltransferase, which metabolises levodopa in both the body in the brain. COMT inhibitors are taken with levodopa + decarboxylase inhibitor to slow down the breakdown of levodopa, thus extending effective duration of levodopa
  • Eg entacapone
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11
Q

Treatment: monoamine oxidase B inhibitors MOA and name examples

A
  • Monoamine oxidase enzymes break down neurotransmitters (dopamine, serotonin and adrenaline) - MOA B enzyme is more specific and doesn’t act on adrenaline or serotonin.
  • MOAB inhibitors block this enzyme and t/f increase circulating dopamine
  • Can be used to help delay the use of levodopa and then in combination with levodopa to reduce required levodopa dose
  • Examples of drugs: selegiline and rasagiline
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12
Q

Treatment: dopamine agonists MOA and SEs

A
  • Mimic dopamine in the basal ganglia and stimulating dopamine receptors but are less effective than levodopa in reducing sx
  • Can be used to delay use of levodopa and then can be used in combination with levodopa to reduce dose of levodopa required.

Important SEs

  • Cause addiction and gambling behaviours (can be extremely traumatic for pt and family)
  • Ergot-derived dopamine agonists cause pulmonary fibrosis: carbergoline and pergolide
  • Use non-ergot derived agonists: ropinirole
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13
Q

How would you differentiate between a PD tremor and a benign essential tremor?

A

PD tremor

  • Asymmetrical, 4-6hz
  • Worse at rest and improves with intentional movement
  • Other PD features are present
  • No change with alcohol

Benign essential tremor

  • Symmetrical, 5-8 Htz
  • Improves at rest and worse with intentional movement
  • No other PD features
  • Improves with alcohol
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14
Q

What is Huntington’s disease?

A
  • Autosomal dominant genetic condition that causes a progressive deterioration in the nervous system.
  • Patients are usually asymptomatic until 30-50 ya (anticipation for next generations)
  • Trinucleotide repeat (CAG) disorder that involves a mutation in the HTT gene on chromosome 4 - leads to accumulation of Huntingtin protein in the striatum (caudate nucleus and putamen)
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15
Q

What is the PC of Huntington’s disease?

A
  • Typically begins with cognitive, psychiatric or mood problems
  • Chorea: involuntary abnormal movements
  • Eye movement disorders
  • Dysarthria
  • Dysphagia
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16
Q

What medications can be given (symptomatic relief) in a patient with Huntington’s? Outline some key aspects of management for patients with this condition

A

Medication:

  • Antipsychotics: eg Olanzapine
  • Benzos
  • Dopamine-depleting agents (tetrabenazine)

Management:

  • Effective breaking bad news
  • MDT: OT, PT, psychology
  • SALT: dysarthria and dysphagia
  • Genetic counselling: pre and post test
  • Advanced directives
  • EoL care planning