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what is MS characterised by?
- plaques of demyelination in the CNS and axon loss
- not PNS
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
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
what is an acute episode of MS?
- optic neuritis
- limitation of activity
how are acute relapses of MS treated?
- steroids: methylprednisolone 1g/24h iv or po for 3d
- NB sparingly as SE
which drugs are used to alter disease progression?
- 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
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
- 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
what is tardive dyskinesia a side effect of?
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)
What is the treatment for EARLY PD?
- dopamine agonist
- delay L-DOPA for as long as posse
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
- 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
what is the side effect of DA agonist?
- nausea: but treated by peripheral DA antag domperidone
- post hypotension
- daytime somnolence
what must apomorphine be given with and why?
- apomorphine is very emetogenic
what are the 2 categories of drugs that inhibit DA metabolism?
- MAO-B inhibitor: selegiline
- COMT inhibitor: tolcapone, entacapone
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
what is dementia?
- chronic confusion
- progressive, irreversible
- memory, thought, mood changes
- dependence on state and carer
what are the 4 common causes of dementia?
- Vacsular (multi-infarct)
- Lewy body dementia
- Fronto-temporal dementia
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?
what are the features of vascular dementia?
- impaired exécutive fonction (choc cake)
- 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?
in vCJD dementia what are the MRI signs?
high signal in posterior thalami
in sCJD what are the EEG signs?
periodic spike and wave