Degenerative Diseases of the CNS

Question 1

what are common features of neurodegenerative diseases?

Answer 1

aetiology largely unknown
(mendelian genetic cases rare, often younger onset)
usually late onset
gradual progression
neuronal loss (specific neuropathology)
structural imaging often normal (atrophy)

Question 2

what is dementia?

Answer 2

Progressive impairment of multiple domains of cognitive function in alert patient leading to loss of acquired skills and interference in occupational and social role

Question 3

what are causes of dementia in late onset (65+)?

Answer 3

Alzheimer’s (55%)
Vascular (20%)
Lewy body (20%)
Others (5%)

Question 4

what are causes of dementia in early onset (<65)?

Answer 4

Alzheimer’s (33%)
Vascular (15%)
Frontotemporal (15%)
Other (33%)

Question 5

what are the “other” causes of dementia?

Answer 5

Toxic (alcohol)
Genetic (Huntington’s)
Infection (HIV, CJD)
Inflammatory (MS)

Question 6

what are treatable causes of dementia?

Answer 6

Vitamin deficiency - B12
Endocrine - thyroid disease
Infective - HIV, syphilis
(however left too long, it becomes untreatable)

Question 7

what are mimics of dementia?

Answer 7

Hydrocephalus
Tumour
Depression: “pseudodementia”

Question 8

what is the diagnostic history and examination of dementia?

Answer 8

History (independent witness) - type of deficit, progression, risk factors, FH
Examination:
cognitive function, neurological, vascular

Question 9

what are the investigations for dementia?

Answer 9

routine - bloods, CT / MRI

others - CSF, EEG, functional imaging, genetics (biopsy)

Question 10

how do you examine cognitive function?

Answer 10

Various domains:
Memory, attention, language, visuospatial,
Behaviour, emotion, executive function
Apraxias, agnosias

Question 11

how can the type of cognitive function help diagnose the cause?

Answer 11

rapid progression (CJD)
stepwise progression (vascular)
abnormal movements (Huntington’s)		
parkinsonism (Lewy body)
myoclonus (CJD)

Question 12

what is Alzheimer’s disease?

Answer 12

Commonest neurodegenerative condition
mean age onset 70 yr 
Temporo-parietal dementia
Early memory disturbance
Language and visuospatial problems
Personality preserved until later

Question 13

describe Frontotemporal dementia

Answer 13

Early change in personality / behaviour
Often change in eating habits
Early dysphasia
Memory / visuospatial relatively preserved

Question 14

what is the non pharmacological symptomatic treatment of dementia?

Answer 14

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

Question 15

what is the pharmacological symptomatic treatment of dementia?

Answer 15

Insomnia
Behaviour (care with antipsychotics)
Depression

Question 16

what is the treatment for Alzheimer’s (+/- Lewy body dementia)?

Answer 16

Cholinesterase inhibitors (cholinergic deficit)
Small symptomatic improvement in cognition (wash-out)
No delay in institutionalisation
NMDA antagonist (memantine)

Question 17

what is the no good evidence treatment for Vascular dementia?

Answer 17

↓ vascular risk factors

Question 18

what is Parkinsonism?

Answer 18

A clinical syndrome with  2 of:
Bradykinesia (slowness of movement)
Rigidity (stiffness)
Tremor (shakiness)
Postural instability (unsteadiness / falls)

Pathology in basal ganglia
predominantly dopamine loss

Question 19

what are the causes of Parkinsonism?

Answer 19

Idiopathic Parkinson’s disease (Dementia with Lewy bodies)
Drug-induced (e.g. dopamine antagonists)
Vascular parkinsonism (lower-half)
Parkinson’s plus syndromes
(Multiple system atrophy)

Question 20

what are the symptoms of Parkinsonism?

Answer 20

Bradykinesia + ≥1 tremor, rigidity, postural instability
Slowly progressive (> 5-10 yrs)
Supported by asymmetric rest tremor, good response to dopamine replacement treatment

Question 21

what are the investigations for Parkinsonism?

Answer 21

Dopamine transporter SPECT

Less dye will bind to transporters as there are less neurones/transporters

Question 22

what is the early medical treatment of PD?

Answer 22

Dopamine agonists
COMT inhibitor
MAO-B inhibitor

Question 23

what causes PD?

Answer 23

associated with loss of dopaminergic neurons

Question 24

what are drug-induced later complications of PD?

Answer 24

Motor fluctuations - levodopa wears off
Dyskinesias - involuntary movements (levodopa)
Psychiatric - hallucinations, impulse control

Question 25

what are non-drug induced later complications of PD?

Answer 25

Depression (20%) 
Dementia (~50% after 10 yrs) 
Autonomic:  BP, bladder, bowel
Speech, swallow
Balance

Question 26

what is the late treatment of PD?

Answer 26

Prolong levodopa half life:	
MAO-B inhibitors 
COMT inhibitor 
slow release levodopa
Add oral dopamine agonist
Continuous infusion (apomorphine, Duodopa)

Functional neurosurgery (deep brain stimulation)