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what is MS characterised by?
- plaques of demyelination in the CNS and axon loss
- not PNS
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what is the presentation of MS?
- unilateral optic neuritis: pain on eye movement and deteriorated central vision
- numbness or tingling in limbs
- leg weakness
- brainstem signs: diplopia
- cerebellar signs: ataxia
- speech problems
- UMN lesion signs
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which investigations need to be done for MS and what would they show?
- MRI: plaques of demyelination
- CSF electrophoresis: oligoclonal bands of IgG
- evoked potentials: DELAYED visual, auditory, somatosensory
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what is an acute episode of MS?
- optic neuritis
- limitation of activity
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how are acute relapses of MS treated?
- steroids: methylprednisolone 1g/24h iv or po for 3d
- NB sparingly as SE
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which drugs are used to alter disease progression?
- INF1beta
- Glatiramer: immunomodulator
- Cytotoxics: mitoxantrone (doxorubicin analogue) for rapidly progressing pts
- Monoclonal antibodies: natalizumab=adhesion molecule inhibitor to stop WBC entering CNS. only for rapidly evolving, severe relapsing remitting MS
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what is parkinson's disease characterised by?
degneration of dopaminergic neurones in substantial nigra that project to striatum
-
what are the cardinal features of PD?
- resting tremor - pill rolling
- cogwheel rigidity
- bradykinesia
- shuffling, festinant gait, no arm swing, hard to start and stop
-
what is the differential diagnosis of parkinsons? clue vodka
- vascular events elsewhere: (stroke, MI) = vascular parkinsons
- orthostatic hypotension and atonic bladder: multi system atrophy (Shy-Drager)
- dementia + vertical gaze paralysis: supranuclear palsy
- kayer-fleisher ring: wilsons disease
- apraxic gait: communicating hydrocephalus
-
what are the features and causes of drug induced parkinsons?
- more likely to be symmetrical
- any drug that blocks action of dopamine
- neuroleptics (rx schizo): clozapine, risperidone
- meds for N&V: metocloperamide, prochlorperazine
- CCB
-
what is tardive dyskinesia a side effect of?
neuroleptic drugs
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what are the principles of treatment in PD?
- restore DA activity
- reduce cholinergic activity
-
what is the first line treatment for LATER PD? and what do you give it with?
- Levo dopa: precursor for DA synthesis, crosses BBB
- combo with benserazide/carbidopa: peripheral DOPA-decarboxylase inhibitor (so cant turn Ldopa into dopamine in periphery)
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What is the treatment for EARLY PD?
- dopamine agonist
- delay L-DOPA for as long as posse
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what are the disadvantages of L-dopa?
- honeymoon period for 5-6 years: early phase of treatment, DA neurones still present and L-dopa can be stored in nerve terminals so it make a physiological concentration
- WITHOUT FLUCUTATION
- chronic use of L-dopa: motor complications - on and off as nerve endings lost
- Dyskinesia
- SE: psychiatric hallucinations, ortho hypotension, nausea
-
give an example of a dopamine agonist and its MOA and use and an advantage
- apomorphine, cabergoline, bromocriptine
- MOA: direct action on DA receptors, mimic endog DA
- adv: long duration of action esp. cabergoline so less fluctuation in symptom control
- early PD: L-DOPA sparing
- later disease: reduce motor fluctuations as an adjunct to L-DOPA
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what is the side effect of DA agonist?
- nausea: but treated by peripheral DA antag domperidone
- post hypotension
- hallucination
- daytime somnolence
- constipation
-
what must apomorphine be given with and why?
- domperidone
- apomorphine is very emetogenic
-
what are the 2 categories of drugs that inhibit DA metabolism?
- MAO-B inhibitor: selegiline
- COMT inhibitor: tolcapone, entacapone
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which is the rationale for using anti-cholinergics in PD? give some e.g. and SE
- rationale: depletion of DA leads to over activity of ACh
- use: improve tremor, stiffness, sialorrhoea, urinary urgency
- eg benzhexol, procyclidine
- SE: dry mouth, blurred vision, urinary retention, constipation, confusion in elderly
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what is dementia?
- chronic confusion
- progressive, irreversible
- memory, thought, mood changes
- dependence on state and carer
-
what are the 4 common causes of dementia?
- Alzheimer's
- Vacsular (multi-infarct)
- Lewy body dementia
- Fronto-temporal dementia
- CJD
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what are the 3 pathological features in Alzheimer's?
- beta amyloid plaques: due to accum of B amyloid peptide, a degradation product of amyloid precursor protein - resulting in progressive neuronal damage
- neurofibrillary tangles
- loss of ACh
- what is the treatment of Alzheimer's?
- cholinesterase inhibitors: donezepil, rivastigmine, galantamine
- NMDA antagonist: memantine (not NICE approved)
-
what are the RF for vascular dementia?
atherosclerosis
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what are the features of vascular dementia?
- impaired exécutive fonction (choc cake)
- apraxia
- emotional lability
- pseudo bulbar palsy (UMNL to corticobulbar path)
- urinary dysfunction
- but preservation of personality
-
what does MRI show in vascular dementia?
diffuse white matter disease
-
what does MRI show in alzheimer's?
atrophy, typically in medial temporal lobes
-
what are the features of fronto-temporal dementia?
- loss of social awareness
- initiation, planning
-
what are the MRI signs of fronto-temporal dementia?
frontal atrophy
-
in vCJD dementia what are the MRI signs?
high signal in posterior thalami
-
in sCJD what are the EEG signs?
periodic spike and wave
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