Neurodegenerative ETC Flashcards
Memory loss over months or years
Dementia
Memory loss over weeks
Depression
Memory loss over days
Infection or stroke
Prevalence of Dementia
Rare if 65 years
20% if >80 years
79% if >100 years
Associated symptoms of dementia
Agitation, aggression, wandering, hallucinations, slow repetitious speech, apathy
Ameliorable metabolic causes of dementia
Hypothyroidism
B12/folate deficiency
Pellegra (tryptophan/nicotinic acid - vit B3 deficit)
Infective causes of dementia
Neurocystericosis
HIV
Syphilis
Whipple’s disease
CNS causes of dementia
PD
Alzheimer’s Disease
Subdural haematoma
Tumours - meningioma
What % of dementia is vascular dementia
25%
What causes vascular dementia
Cumulative effects of many mini-strokes
Sudden onset and stepwise progression are features
3rd most common cause of dementia?
Lewy Body Dementia
Fluctuating cognitive impairment
with visual hallucinations
Followed by parkinsonism
Signs of fronto-temporal dementia
Executive impairment
Behavioural/personality changes early on
Early preservation of episodic memory
Disinhibition and emotional unconcern
Medication for disinhibition/altered behaviour in dementia
Trazodone (antipsychotic) or lorazepam
If worse - quetiapine, risperidone, olanzapine - but will worsen cognition
Haloperidol used short-term
Medication for depression in dementia
SSRI eg. citalopram
Drugs to avoid in dementia
Neuroleptics/antipsychotics, sedatives, tricyclics
These all impair cognition
Main features of AD
Progressive global cognitive impairment Visuo-spatial skill decrease Memory loss Decreased verbal abilities Executive function (planning)
What is anosognosia?
Lack of insight into the problems engendered by the disease
Pathology of AD
B-amyloid accumulation in amyloid plaques
Neurofibrillary tangles
Decreased acetylcholine
Risk factors for AD
1st degree relative with AD
Down’s syndrome (AD inevitable)
ApoE E4 allele homozygote
Vascular risk factors - vascular dementia in 95% of AD patients
Low physical or cognitive activity
Depression
Loneliness
Smoking >20 cigarettes a day accelerates onset by 2.3years
Prognosis of AD
Mean survival is 7 years from onset of unequivocal symptoms
Medication in AD
Acetylcholinesterase inhibitors
Appear to help more with laying down of new memories than the conservation of old memories
Seem to help in dementia of PD and LB dementia
Eg. Donepezil, Rivastigmine, Galantamine
Side effects of acetylcholinesterase inhibitors
Worsen peptic ulcer disease and heart block
D&V, cramps
Incontinence
Headaches , dizziness, insomnia
Another non-Ach medication in AD
Memantine
NMDA antagonist
Reasonably effective in late stage disease
3 primary features of Parkinsonism
Tremor - resting tremor, pill-rolling
Rigidity - Cogwheel rigidity
Bradykinesia - slow to initiate movement and slow movement
Therefore festinating gait (decreased arm swing)
Micrographia
Expressionless face
Monotonous hypophonic speech
Typical age of onset of PD
65 years
Pathology of PD
Mitochondrial DNA dysfunction leads to degeneration of dopaminergic neurons in the SN of the BG
Features of bradykinesia in PD
Progressive fatiguing - decrement in amplitude of repetitive movement
Upper limb usually affected first and is unilateral
Features of tremor in PD
Unilateral in upper limb then to lower limb on that side and then to other arm
Made worse by emotion or stress
Unmasking - overflow - count backwards from 10
Features of rigidity of PD
Unmasked - synkinesis - get to move other arm
Also called reinforcement
Features of posture and gait in PD
Postural instability and hypotension - not usually present in first 5 years of disease
Feature which may lead to death in PD
Speech and swallowing difficulties - therefore aspiration pneumonia as terminal event
Sleep in PD
REM Behaviour Disorder
Talking and thrashing out in sleep with no recollection
Treat with clozapine or quetiapine
Main medication in PD
L-DOPA
Given with domperidone to prevent nausea and vomiting
Also Carbidopa or Benserazide to prevent peripheral conversion
Levodopa extender
Entacapone
COMT inhibitor
DA agonists
Ropinirole and pramipexole
Rotigotine patches
Bromocriptine/pergolide and cabergoline - not really used because can cause heart problems and lung fibrosis
Preventing breakdown of dopamine at synapse
Selegeline and rasagiline
MAOinhibitors
Management of LDOPA induced dyskinesia
Amantadine
Anticholinergics - Benzhexol and Orphenadrine
Treatment of ON-OFF
Apomorphine - short-acting DA agonist
L-Dopa intestinal gel infusion pump
Avoid protein rich meals - prevents levodopa absorption
Features of Progressive Supranuclear Palsy
Postural instability early on
Pseudobulbar palsy
Vertical supranuclear gaze palsy (can’t look up or down)
Also dementia and parkinsonism
Little response to L-DOPA (but parkinsonian features may respond)
Features of Multi-System Atrophy
Parkinsonism is more symmetrical and WITHOUT TREMOR
Autonomic failure - severe
Olivopontocerebellar atrophy - cerebellar signs
PD features may respond but Ldopa
Cortico basal degeneration features
Alien limb phenomenon
Myoclonus
PD signs and dementia
LDOPA has no effect
What type of tremor caused by cerebellar problems?
Intention tremor
What is a essential tremor, two types and what causes it?
Postural - when limb held out against gravity
Kinetic - present on movement
eg. Benign essential tremor Thyrotoxicosis Anxiety B-agonists
Essential - improves with alcohol
Causes of chorea
and treatment
Huntingtons Sydenhams chorea (strep)
Thyrotoxicosis
SLE
Dopamine blocking drugs or treat underlying disorder
Egs of Tics
and treatment
Tourettes (motor and vocal)
Physical tics
Clonazepam and clonidine if severe
Dystonia examples
Primary dystonia - children/young adult, usually starts with foot and then spreads - treat with DBS
Focal dystonias - torticollis - writers cramp, blepharospasm - worsened by stress - treat with BOTOX
