Neuro - Parkinson's Disease, Parkinsonism and Huntington’s disease Flashcards
List some causes of Parkinsonism
-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
What is MSA?
- 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
What is corticobasal degeneration?
- 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
What is PSP?
- 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
What is PD? Describe the pathophysiology
- 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).
What are the three key features of PD? Name other possible features
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
What investigations should you perform on a patient with suspected PD?
- 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
Name some treatments available for PD
- Levodopa
- COMT inhibitors
- Dopamine agonists
- MOA-B inhibitors
Treatment: synthetic dopamine MOA and SEs
- 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
Treatment: COMT inhibitors MOA
- 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
Treatment: monoamine oxidase B inhibitors MOA and name examples
- 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
Treatment: dopamine agonists MOA and SEs
- 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
How would you differentiate between a PD tremor and a benign essential tremor?
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
What is Huntington’s disease?
- 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)
What is the PC of Huntington’s disease?
- Typically begins with cognitive, psychiatric or mood problems
- Chorea: involuntary abnormal movements
- Eye movement disorders
- Dysarthria
- Dysphagia
