Degenerative Diseases of the CNS Flashcards
What are the common features of neurodegenerative diseases?
- Aetiology largely unknown
- > rarely mendelian genetic cases: often younger onset
- Usually late onset
- Gradual progression
- Neuronal loss (specific neuropathology)
- Structural imaging often normal (atrophy)
What is the definition of Dementia?
Progressive impairment of multiple domains of cognitive function in alert patient, leading to loss of acquired skills and interference in occupational and social role
What are the main aetiologies of Young onset vs. Late onset Dementia?
- often mixed pathology*
- Young onset (<65 yrs)
- > Alzheimer’s (most common)
- > Vascular
- > Frontotemporal (MND/ALS)
- > Other: toxic, genetic (ie. Huntington’s), infection (HIV, CJD), inflammatory (MS)
- Late onset (>65yrs)
- > Alzheimer’s (most common)
- > Vascular
- > Lewy Body
- > Others
What are the treatable causes of Dementia?
- Vit B12 deficiency
- Thyroid disease (endocrine)
- Infective: HIV, Syphilis
What is the differential diagnosis of Dementia?
- use a brain CT scan to exclude these pathologies!*
- Hydrocephalus
- Tumour
- Depression: “pseudodementia”
How do you make the diagnosis of Dementia?
- History (independent witness)
- Examination:
- > cognitive function:
- various domains: memory, attention, visuospatial, behaviour, emotion, executive function, apraxias, agnosias
- screening tests (MMSE, MoCA)
- neurophysiological assessment
- > neurological
- > vascular
- Investigations:
- > routine: bloods, CT (first-line), MRI
- > others: CSF, EEG, functional imaging, genetics
Which additional clinical features would raise suspicion of Huntington’s Dementia?
- Abnormal movements
Which additional clinical features would raise suspicion of Lewy Body Dementia?
- Parkinsonism
Which additional clinical features would raise suspicion of CJD Dementia?
- Rapid progression
- Myoclonus
Which additional clinical features would raise suspicion of Vascular Dementia?
- Stepwise progression
What is the most common neurodegenerative disease?
Alzheimer’s disease
Temporo-parietal Dementia
Which features are pathognomonic for Alzheimer’s disease?
- Beta-amyloid plaques
- Neurofibrillary tangles
What are the clinical features of Alzheimer’s?
- Temporo-parietal Dementia
- Early change in memory disturbance
- Language and Visuospatial problems
- Personality preserved until later (frontal lobe)
Which feature is pathognomonic for Frontotemporal Dementia?
Tau protein
What are the clinical features of Frontotemporal Dementia?
- Early change in personality + behaviour -> often changes in eating habits
- Early change in dysphasia (Broca’s)
- Memory/visuospatial relatively preserved
Which feature is pathognomonic for Lewy Body Dementia?
Lewy Body
What are the clinical features of Lewy body Dementia?
- Early visuospatial and executive dysfunction
- Prominent fluctuating cognition
- Parkinsonism and Visual Hallucinations common
What is the general treatment of Dementia?
Non-Pharmacological:
- info and support, dementia services
- OT
- social work, support, respite, placement
Pharmacological:
- Insomnia
- Behavioural - antipsychotics
- Depression
What is the specific treatment of Alzheimer’s +/- Lewy body Dementia?
- Cholinesterase inhibitors:
- > donepezil, rivastigmine, galantamine
- NMDA antagonists: (glutamate antagonists)
- > memantime
What is the specific treatment of Frontotemporal Dementia?
NONE
What is the specific treatment of Vascular Dementia?
- No robust evidence for decreasing vascular risk factors
What is the diagnosis of Parkinson’s?
Clinical (!!) syndrome with ≥2 of:
- Bradykinesia (slowness of movement)
- Rigidity (stiffness)
- Unilateral At-Rest Tremor (shakiness)
- Postural instability (unsteadiness/falls)
What are the clinical features of Parkinson’s?
- In the Subsantia Nigra - Basal Ganglia
- Predominantly Dopamine loss
- Lewy bodies (alpha-synuclein)
What are the different clinical types of Parkinson’s disease?
- Idiopathic Parkinson’s disease
- > Dementia w Lewy bodies
- Drug-induced Parkinson’s disease
- Vascular Parkinsonism (lower-half)
- Parkinson’s plus syndromes:
- > Multiple system atrophy
- > Progressive supranuclear palsy / corticobasal degeneration
What are the clinical features of Parkinson’s disease?
Cardinal signs:
- Tremor -> unilateral, at-rest
- Bradykinesia -> progressive decrement
- Postural Instability
Non-Motor Symptoms:
- Anosmia
- REM sleep behaviour disorder
- Autonomic (constipation, urinary, bowel, sexual)
- Neuropsychiatric (hallucinations, cognitive)
- Depression, fatigue, pain
What is the imaging of choice for Parkinson’s disease?
Dopamine Transporter SPECT
What is the treatment for Parkinson’s disease?
Early medical treatment:
- Levodopa (!!!)
- COMT inhibitor
- MAO-B inhibitor
- Dopamine agonists
Late treatment: (time-critical)
- Prolong Levodopa half-life
- > MAO-B inhibitors
- > COMT inhibitors
- > slow-release Levodopa
- Add oral Dopamine agonist
- Continuous infusion
- Functional neurosurgery (deep brian stimulation)
- Allied health professionals +/- care package
What are the side-effects of Levodopa?
- Motor fluctuations:
- > levodopa wears off
- Dyskinesias:
- > involuntary movements
- Psychiatric:
- > hallucinations
- > impulse control
What are the later complications of Parkinson’s disease?
- Balance/falls/fractures
- Dementia (50% after 10yrs)
- Speech, swallow
- Gait freezing
