Degenerative Diseases of the CNS

Question 1

what is very typical of neurodegenerative diseases?

Answer 1

usually late onset and have gradual progression

Question 2

what is dementia?

Answer 2

a syndrome consisting of progressive impairment of multiple domains of cognitive function in alert patients leading to loss of acquired skills and interference in occupation and social role

Question 3

what are the causes of dementia?

Answer 3

late onset (>65)= Alzheimer's, vascular, Lewy body
young onset (<65)= Alzheimer's, vascular, frontotemporal and other

Question 4

how is dementia diagnosed?

Answer 4

history= type of deficit, progression, risk factors and FH

Question 5

how is someone with dementia examined?

Answer 5

cognitive function, neurological and vascular

Question 6

what investigations are performed fro suspected dementia?

Answer 6

bloods, CT/MRI (see patterns of atrophy), CSF (inflammatory case and biomarkers for Alzheimer’s), EEG, functional imaging and genetics

Question 7

what is Alzheimers disease?

Answer 7

commonest neurodegenerative condition, mean age onset= 70 and caused by beta-amyloid plaques and neurofibrillary tangles

Question 8

how is Alzheimers disease treated?

Answer 8

cholinesterase inhibitors increase cholinergic function= donepezil, rivastigmine, galantamine and NMDA antagonists have a similar role eg memantine

Question 9

what is frontotemporal dementia?

Answer 9

disorder of tau pathology, early change in personality and behaviour

Question 10

what is dementia with Lewy bodies?

Answer 10

pathology of Lewy bodies= accumulations of the abnormal alpha synuclein

Question 11

what is Parkinsonism?

Answer 11

a clinical syndrome with >= of bradykinesia (slowness of movement), rigidity (stiffness), tremor and postural instability (unsteadiness)

Question 12

what is the pathology of Parkinsonism?

Answer 12

progressive reduction of dopamine in the basal ganglia of the brain leading to disorders of movement– symptoms are asymmetrical and one side is affected more that the other

Question 13

how do we determine the difference between a Parkinson’s tremor and a benign essential tremor?

Answer 13

a parkinsons tremor is asymmetrical, worse at rest, no change with alcohol and improves with intentional movement and a BET is symmetrical, improves with rest, worse with intentional movement and improves with alcohol

Question 14

how does Parkinson’s typically present?

Answer 14

older aged man, unilateral tremor (pill-rolling), cogwheel rigidity, bradykinesia (describes how their movements get slower and smaller)

Question 15

how is Parkinson’s diagnosed?

Answer 15

symptoms and examination

Question 16

what are Parkinson’s plus syndromes?

Answer 16

neurodegenerative disorders which have additional atypical features to distinguish them from idiopathic Parkinson’s disease

Question 17

what is multiple system atrophy?

Answer 17

neurones in multiple systems in the brain degenerate - if affects basal ganglia will present like Parkinson’s but can cause autonomic or cerebellar dysfunction

Question 18

what is dementia with Lewy bodies?

Answer 18

a type of dementia with features of Parkinson’s, causes progressive cognitive decline, hallucinations, delusions, disorders of REM sleep and fluctuating consciousness

Question 19

what is progressive supra nuclear palsy?

Answer 19

progressive cognitive decline and an eye movement disorder called supranucelar gaze palsy

Question 20

what is corticobasal degeneration?

Answer 20

gives cortical signs and Parkinsonism from basal ganglia involvement

Question 21

what are risk factors for Parkinson’s?

Answer 21

LRRK2 (autosomal dominant= late onset), Parkin (recessive= young onset), GBA (involves Gaucher’s disease), pesticides (increase risk), smoking and caffeine (decrease risk)

Question 22

what functional imaging can be used for Parkinson’s?

Answer 22

dopamine transported SPECT scan - radioisotope binds to the dopamine transporter on dopaminergic cells in the brain (strongly in the basal ganglia) - will distinguish between PD and essential tremor

Question 23

how is Parkinson’s managed?

Answer 23

cannot be cured so treat symptoms, usually give levodopa which boost dopamine levels and combined with a drug which prevents its breakdown before it enters the brain eg carbidopa and benserazide

Question 24

what are the possible side-effects of levodopa?

Answer 24

gets less effective over time and when the dose is too high can cause dyskinesia which are abnormal movements associated with excessive motor activity

Question 25

what is the role of COMT inhibitors?

Answer 25

slows the breakdown of levodopa so extending its effective duration eg entacapone

Question 26

what is the role of dopamine agonists?

Answer 26

these mimic dopamine in the basal ganglia and stimulate the dopamine receptors, they are less effective than levodopa but are usually used to delay the use of levodopa and then used in combination to reduce the dose of levodopa eg pergolide and carbergoline - possible side effect= pulmonary fibrosis

Question 27

what is the role of MOA-B inhibitors?

Answer 27

breaks down dopamine and so helps increase the circulating dopamine eg selegiline, rasagiline