Degenerative Diseases of the CNS

Question 1

Common features of neurodegenerative diseases

Answer 1

Aetiology largely unknown 
Usually late onset 
Gradual progression 
Neuronal loss 
Structural imaging often normal

Question 2

What is dementia?

Answer 2

A syndrome consisting of progressive impairment of multiple domains of cognitive function in an alert patient, leading to loss of acquired skill and interference in occupational and social roles

Question 3

What is the incidence of dementia?

Answer 3

200 per 100,000

Question 4

Prevalence of dementia

Answer 4

1,500 per 100,000

Question 5

What is Parkinsonism?

Answer 5

Clinical syndrome with 2 or more of;
Bradykinesia 
Rigidity 
Tremor 
Postural instability

Question 6

Cause of Parkisonism

Answer 6

Pathology in the basal ganglia, predominantly dopamine loss

Question 7

Incidence of Parkinsonism

Answer 7

15-20 per 100,000 per year

Question 8

Causes of late onset dementia (65+)

Answer 8

Alzheimer’s disease
Vascular causes
Lewy body
Others

Question 9

Causes of young onset dementia (< 65)

Answer 9

Alzheimer’s disease
Vascular causes
Frontotemporal causes
Other e.g. toxic, genetic, infection, inflammatory

Question 10

Presentation of Alzheimer’s disease

Answer 10

Commonest neurodegenerative condition 
Temperoparietal dementia 
Early memory disturbance 
Language and visuospatial problems 
Personality preserved until later

Question 11

Presentation of frontotemporal dementia

Answer 11

Early changes in personality/behaviour e.g. loss of inhibition, violence, sexually explicit
Changes in eating habits
Early dysphasia
Memory/visuospatial awareness relatively preserved

Question 12

Treatable causes of dementia

Answer 12

Vitamin B12 deficiency
Endocrine e.g. thyroid disease, hypothyroidism
Infective e.g. HIV, syphilis
Mimics e.g. hydrocephalus, tumour, depression

Question 13

Causes of Parkinsonism

Answer 13

Idiopathic Parkinson’s disease
Drug-induced e.g. dopamine antagonists
Vascular Parkinsonism
Parkinson’s plus syndromes

Question 14

How do Parkinson’s plus syndromes present?

Answer 14

Spasticity 
Weakness 
Incontinence 
Progressive supranuclear palsy 
Corticobasal degeneration 
Multiple system atrophy

Question 15

Domains of cognitive function examined when diagnosing dementia/Parkinsonism

Answer 15

Memory 
Attention
Language 
Visuospatial 
Behaviour 
Emotion 
Executive function 
Apraxias 
Agnosias

Question 16

Screening tests for dementia/Parkinsonism

Answer 16

Mini-mental state examination (MMSE)

Montreal (MOCA)

Question 17

Clues to diagnosis of dementia/Parkinsonism

Answer 17

Type of cognitive deficit
Speed of progression (rapid or stepwise)
Other neurological signs e.g. abnormal movements - Huntington’s disease

Question 18

How is dementia diagnosed?

Answer 18

History - independent witness, type of deficit, progression, risk factors, FH
Examination - cognitive function, neurological and vascular
Investigations - routine bloods, CT/MRI, CSF, EEG, functional imaging, genetics

Question 19

Clinical diagnosis of Parkinson’s disease

Answer 19

Must have bradykinesia and at least one of; tremor, rigidity, postural instability
No other cause/atypical features
Slowly progressive
Supported by asymmetric rest tremor
Good response to dopamine replacement treatment
Loss of facial expression

Question 20

When is Parkinson’s disease less likely as a diagnosis?

Answer 20

Rapid progression 
Symmetrical 
Lack of rest tremor 
Poor response to treatment 
Early falls 
Early dementia 
Abnormal neurological signs

Question 21

Describe the Parkinsonian gait

Answer 21

Small stride
Loss of arm swing
Slight stoop

Question 22

Non-pharmacological symptomatic treatment of dementia

Answer 22

Information and support, dementia services
Occupational therapy
Social work, support, respite, placement
Voluntary organisations

Question 23

Symptomatic features of dementia that can be treated pharmacologically

Answer 23

Insomnia
Behavioural issues
Depression

Question 24

Treatment for Alzheimer’s +/- Lewy Body dementia

Answer 24

Cholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine - small symptomatic improvement in cognition
NMDA antagonist e.g. memantine

Question 25

Parkinson's disease treatment

Answer 25

Revolves around loss of dopaminergic neurones Levodopa and carbidopa/benserazide Dopamine agonists e.g. ropinirole, pramipexole, rotigotine MAO-B inhibitors e.g. selegiline, rasagiline, safinamide

Question 26

Why might levodopa and carbidopa/benserazine given to treat Parkinson's disease?

Answer 26

Levodopa can cross the blood-brain barrier and drive the uptake system in the neurones so that the remaining neurones produce more dopamine Carbidopa/Benserazine are enzyme blockers so prevent the metabolism of levodopa peripherally

Question 27

Why might MAO-B inhibitors be given to treat Parkinson's disease?

Answer 27

Some dopamine in the brain is broken down by MAO-B enzyme so the inhibitor blocks the loss of dopamine via this pathway

Question 28

Drug induced complications of Parkinson's disease

Answer 28

Fluctuations in motor symptoms in long-term use of levodopa Dyskinesias Increased impulsivity due to dopamine replacement e.g. excessive spending of money, unsafe sexual activity

Question 29

Non-drug induced later complications of Parkinson's disease

Answer 29

``` Depression Dementia Autonomic side effects e.g. postural hypertension, bladder and bowel problems Speech problems Swallowing problems Balance problems ```

Question 30

Later treatment of Parkinson's disease

Answer 30

Prolong levodopa half-life e.g. MAO-B inhibitors, COMT inhibitor, slow-release levodopa Add oral dopamine agonist Continuous infusion of apomorphine/duodopa Functional neurosurgery Allied health professionals, care package