neurodegenerative diseases Flashcards
what is multiple sclerosis
inflammatory demyelinating disorder of the CNS
who usually presents with MS
females aged 20-50
name some environmental factors associated with MS
viral infections e.g. EBV and vitamin D deficiency
smoking, latitude, diet and obesity in early life
pathophysiology of MS
autoimmune disease that causes accumulation of plaques of demyelination in the white matter of the CNS
+ gliosis (scarring)
what is the most common first presentation of MS
optic neuritis
clinical presentation of optic neuritis
unilateral decrease in visual acuity, poor discrimination of colours, pain worse on eye movement, RAPD, central scotoma
fundoscopy of optic neuritis
pale, swollen disc
what are the 3 main patterns of disease in MS
relapsing remitting
secondary progressive
primary progressive
what is the most common pattern of disease in MS
relapsing remitting
relapsing remitting MS
episodes or exacerbations of symptoms followed by periods of recovery
secondary progressive MS
RR patients who have deteriorated and develop signs and symptoms between relapses
primary progressive MS
steady progression and worsening of the disease from the onset (without remissions)
how is a relapse of MS defined
onset of new symptoms or worsening of existing ones, lasting longer than 24hrs in the absence of infection or any other cause, after a stable period of at least a month
what is a common complication of progressive MS and why
urinary frequency, urgency and incontinence
due to neurogenic detrusor overactivty
clinical presentation of MS
paraesthesia, weakness, balance and mobility issues, fatigue, stiffness or spasms
investigations for MS
CSF, MRI, bloods
CSF positive finding of MS
oligoclonal bands of IgG
MRI positive finding of MS
periventricular white matter lesions
acute management of MS
glucocorticoids -> methylprednisolone
what does NMOSD stand for
neuromyelitis optica spectrum disorder
what is NMOSD
inflammatory disease of the CNS that causes demyelination of the optic nerve and spinal cord
who usually presents with NMOSD
females, mid 30s
what can NMOSD often be mistaken for
multiple sclerosis
how can we differentiate between MS and NMOSD
presence of aquaporin 4 antibodies
acute management of NMOSD
high dose steroids
(plasma exchange if needed)
chronic management of NMOSD
immunosuppression with steroid-sparing agents e.g. azathioprine
who is more likely to develop MND
males (slightly!)
what is the most common type of MND in adults
amyotrophic lateral sclerosis
what is the average survival time for a patient diagnosed with MND
3 years
what is often associated with MND
frontotemporal dementia
what is the main cause of death in patients with MND
weakness of respiratory muscles
where is predominantly affected by MND
upper and lower motor neurones in the spinal cord, cranial nerve motor nuclei and cortex
name some upper motor neuron signs
increased tone, hyper-reflexia, spastic gate, slowed movements
name some lower motor neuron signs
muscle wasting, weakness, FASCICULATIONS, absent or reduced deep tendon reflexes
what sign is associated with greater functional decline in MND
catabolism (hypermetabolism)
what are the 4 main types of MND
spinal ALS
bulbar ALS
progressive muscular atrophy
primary lateral sclerosis
what is split hand syndrome
preferential wasting of the thenar group (guttering) typically seen in ALS
clinical presentation of spinal ALS
upper and lower motor neuron symptoms
e.g. spasticity, hyperreflexia, fasciculations, muscle
atrophy
usually in one limb
who presents with bulbar ALS
men aged 60-80
clinical presentation of bulbar ALS
early tongue and bulbar involvement
dysarthria, dysphagia, nasal regurgitation of fluids and choking
clinical presentation of progressive muscular atrophy
ONLY LOWER MOTOR NEURONE FEATURES
weakness, muscle wasting, fasciculations
clinical presentation of primary lateral sclerosis
ONLY UPPER MOTOR NEURONE FEATURES
management of MND
supportive - MDT, pain relief, SLT involvement
disease-modifying treatment in MND and what it does
riluzole - extends life expectancy by around 3 months
what is Creutzfeldt-Jakob disease
a neurodegenerative disorder caused by prion proteins
what are prions
misfolded proteins that induce normal proteins within the brain to misfold and aggregate, leading to neuronal loss
genetics involved with Creutzfeldt-Jakob disease
PRNP gene mutation
clinical presentation of Creutzfeldt-Jakob disease
rapidly progressive dementia, sleep disturbances, aphasia, apraxia, tremor, dystonia
how do we confirm suspected Creutzfeldt-Jakob disease and when is investigation indicated
brain tissue biopsy
only indicated if there is a reversible condition suspected in the differential
management of Creutzfeldt-Jakob disease
symptom control and palliative care
what is the most common type of dementia
alzheimers
what are the 4 main types of dementia
alzheimers
frontal lobe
lewy body
vascular
name some secondary causes of dementia
brain infection, haematoma, normal pressure hydrocephalus, alcohol dementia, deficiencies
clinical presentation of normal pressure hydrocephalus
triad of gait disturbance, dementia and urinary incontinence
normal pressure hydrocephalus on imaging
ventricular enlargement
what causes alzheimers disease
build up of amyloid protein deposits around brain cells and tau protein tangles within brain cells
which type of dementia is liked to down syndrome
alzheimers
what is vascular dementia
brain damage due to cerebrovascular disease
how will vascular dementia present
usually later onset
presence of CVD + a clear temporal relationship between the onset of dementia and CVD
what causes lewy body dementia
deposition of abnormal protein (a-synuclein) with neurons in the brainstem and neocortex
what is the key area of the brain affected in lewy body dementia
substantia nigra
inheritance seen in huntingtons
autosomal dominant
name some secondary causes of dementia (with the mnemonic)
VITAMINS
vascular
infection
trauma
alcohol and drugs
metabolic (thyroid)
intracranial SOLs
nutritional deficiencies
SOLs
which genetic phenomena does huntingtons demonstrate and what is it
anticipation - each generation develops a genetic disease at an earlier age
clinical presentation of alzheimers
gradual onset, decline of short-term memory
autobiographical memory usually preserved
poor concentration, sleep and low mood
clinical presentation of vascular dementia
step-wise deterioration, dysphasia, dyscalculia
how does fronto-temporal dementia present
cognitive impairment, personality change, disinhibition
which type of dementia is associated with constructional apraxia
fronto-temporal dementia
how does dementia with lewy bodies present
visual hallucinations, fluctuating cognition, REM sleep behaviour disorder
which cognitive assessment is used for suspected dementia
addenbrooks
what can be a good tool for differentiating between alzheimers and vascular dementia
hachinski ischaemic score
what is huntington’s disease
genetic disorder that causes progressive breakdown of nerve cells in the brain
which area of the brain is most commonly degenerated in huntington’s disease
basal ganglia
what is the classic triad patients with huntington’s present with
choreoathetosis, dementia and psychiatric abnormalities e.g. depression
what is choreoathetosis
unpredictable, flowing and writhing movements
management of the symptoms of huntington’s
chorea: tetrabenazine
depression: SSRIs
standard imaging for suspected dementia
CT
management of severe alzheimers
memantine
mechanism of action of memantine
NMDA receptor blocker
name some other drugs used to manage alzheimers and their mechanism of action
cholinesterase inhibitors
donepezil, rivastigmine, galantamine
management of vascular dementia
manage risk factors +/- cholinesterase inhibitors
