Degenerative Diseases of the CNS Flashcards
Common features of neurodegenerative diseases
Aetiology largely unknown Usually late onset Gradual progression Neuronal loss Structural imaging often normal
What is dementia?
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
What is the incidence of dementia?
200 per 100,000
Prevalence of dementia
1,500 per 100,000
What is Parkinsonism?
Clinical syndrome with 2 or more of; Bradykinesia Rigidity Tremor Postural instability
Cause of Parkisonism
Pathology in the basal ganglia, predominantly dopamine loss
Incidence of Parkinsonism
15-20 per 100,000 per year
Causes of late onset dementia (65+)
Alzheimer’s disease
Vascular causes
Lewy body
Others
Causes of young onset dementia (< 65)
Alzheimer’s disease
Vascular causes
Frontotemporal causes
Other e.g. toxic, genetic, infection, inflammatory
Presentation of Alzheimer’s disease
Commonest neurodegenerative condition Temperoparietal dementia Early memory disturbance Language and visuospatial problems Personality preserved until later
Presentation of frontotemporal dementia
Early changes in personality/behaviour e.g. loss of inhibition, violence, sexually explicit
Changes in eating habits
Early dysphasia
Memory/visuospatial awareness relatively preserved
Treatable causes of dementia
Vitamin B12 deficiency
Endocrine e.g. thyroid disease, hypothyroidism
Infective e.g. HIV, syphilis
Mimics e.g. hydrocephalus, tumour, depression
Causes of Parkinsonism
Idiopathic Parkinson’s disease
Drug-induced e.g. dopamine antagonists
Vascular Parkinsonism
Parkinson’s plus syndromes
How do Parkinson’s plus syndromes present?
Spasticity Weakness Incontinence Progressive supranuclear palsy Corticobasal degeneration Multiple system atrophy
Domains of cognitive function examined when diagnosing dementia/Parkinsonism
Memory Attention Language Visuospatial Behaviour Emotion Executive function Apraxias Agnosias
Screening tests for dementia/Parkinsonism
Mini-mental state examination (MMSE)
Montreal (MOCA)
Clues to diagnosis of dementia/Parkinsonism
Type of cognitive deficit
Speed of progression (rapid or stepwise)
Other neurological signs e.g. abnormal movements - Huntington’s disease
How is dementia diagnosed?
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
Clinical diagnosis of Parkinson’s disease
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
When is Parkinson’s disease less likely as a diagnosis?
Rapid progression Symmetrical Lack of rest tremor Poor response to treatment Early falls Early dementia Abnormal neurological signs
Describe the Parkinsonian gait
Small stride
Loss of arm swing
Slight stoop
Non-pharmacological symptomatic treatment of dementia
Information and support, dementia services
Occupational therapy
Social work, support, respite, placement
Voluntary organisations
Symptomatic features of dementia that can be treated pharmacologically
Insomnia
Behavioural issues
Depression
Treatment for Alzheimer’s +/- Lewy Body dementia
Cholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine - small symptomatic improvement in cognition
NMDA antagonist e.g. memantine
Parkinson’s disease treatment
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
Why might levodopa and carbidopa/benserazine given to treat Parkinson’s disease?
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
Why might MAO-B inhibitors be given to treat Parkinson’s disease?
Some dopamine in the brain is broken down by MAO-B enzyme so the inhibitor blocks the loss of dopamine via this pathway
Drug induced complications of Parkinson’s disease
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
Non-drug induced later complications of Parkinson’s disease
Depression Dementia Autonomic side effects e.g. postural hypertension, bladder and bowel problems Speech problems Swallowing problems Balance problems
Later treatment of Parkinson’s disease
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
