Degenerative Diseases of the CNS Flashcards
what is very typical of neurodegenerative diseases?
usually late onset and have gradual progression
what is dementia?
a syndrome consisting of progressive impairment of multiple domains of cognitive function in alert patients leading to loss of acquired skills and interference in occupation and social role
what are the causes of dementia?
late onset (>65)= Alzheimer's, vascular, Lewy body young onset (<65)= Alzheimer's, vascular, frontotemporal and other
how is dementia diagnosed?
history= type of deficit, progression, risk factors and FH
how is someone with dementia examined?
cognitive function, neurological and vascular
what investigations are performed fro suspected dementia?
bloods, CT/MRI (see patterns of atrophy), CSF (inflammatory case and biomarkers for Alzheimer’s), EEG, functional imaging and genetics
what is Alzheimers disease?
commonest neurodegenerative condition, mean age onset= 70 and caused by beta-amyloid plaques and neurofibrillary tangles
how is Alzheimers disease treated?
cholinesterase inhibitors increase cholinergic function= donepezil, rivastigmine, galantamine and NMDA antagonists have a similar role eg memantine
what is frontotemporal dementia?
disorder of tau pathology, early change in personality and behaviour
what is dementia with Lewy bodies?
pathology of Lewy bodies= accumulations of the abnormal alpha synuclein
what is Parkinsonism?
a clinical syndrome with >= of bradykinesia (slowness of movement), rigidity (stiffness), tremor and postural instability (unsteadiness)
what is the pathology of Parkinsonism?
progressive reduction of dopamine in the basal ganglia of the brain leading to disorders of movement– symptoms are asymmetrical and one side is affected more that the other
how do we determine the difference between a Parkinson’s tremor and a benign essential tremor?
a parkinsons tremor is asymmetrical, worse at rest, no change with alcohol and improves with intentional movement and a BET is symmetrical, improves with rest, worse with intentional movement and improves with alcohol
how does Parkinson’s typically present?
older aged man, unilateral tremor (pill-rolling), cogwheel rigidity, bradykinesia (describes how their movements get slower and smaller)
how is Parkinson’s diagnosed?
symptoms and examination
what are Parkinson’s plus syndromes?
neurodegenerative disorders which have additional atypical features to distinguish them from idiopathic Parkinson’s disease
what is multiple system atrophy?
neurones in multiple systems in the brain degenerate - if affects basal ganglia will present like Parkinson’s but can cause autonomic or cerebellar dysfunction
what is dementia with Lewy bodies?
a type of dementia with features of Parkinson’s, causes progressive cognitive decline, hallucinations, delusions, disorders of REM sleep and fluctuating consciousness
what is progressive supra nuclear palsy?
progressive cognitive decline and an eye movement disorder called supranucelar gaze palsy
what is corticobasal degeneration?
gives cortical signs and Parkinsonism from basal ganglia involvement
what are risk factors for Parkinson’s?
LRRK2 (autosomal dominant= late onset), Parkin (recessive= young onset), GBA (involves Gaucher’s disease), pesticides (increase risk), smoking and caffeine (decrease risk)
what functional imaging can be used for Parkinson’s?
dopamine transported SPECT scan - radioisotope binds to the dopamine transporter on dopaminergic cells in the brain (strongly in the basal ganglia) - will distinguish between PD and essential tremor
how is Parkinson’s managed?
cannot be cured so treat symptoms, usually give levodopa which boost dopamine levels and combined with a drug which prevents its breakdown before it enters the brain eg carbidopa and benserazide
what are the possible side-effects of levodopa?
gets less effective over time and when the dose is too high can cause dyskinesia which are abnormal movements associated with excessive motor activity
what is the role of COMT inhibitors?
slows the breakdown of levodopa so extending its effective duration eg entacapone
what is the role of dopamine agonists?
these mimic dopamine in the basal ganglia and stimulate the dopamine receptors, they are less effective than levodopa but are usually used to delay the use of levodopa and then used in combination to reduce the dose of levodopa eg pergolide and carbergoline - possible side effect= pulmonary fibrosis
what is the role of MOA-B inhibitors?
breaks down dopamine and so helps increase the circulating dopamine eg selegiline, rasagiline
