Neurodegenerative conditions Flashcards
What are the symptoms of AD?
Progressive, global impairment
- cognition
- visuo-spatial skills
- memory
- verbal skills
- planning
Later: mood changes, depression, psychosis, behaviour changes, agnosis
What are the symptoms of vascular dementia?
Cumulative effect of many small strokes
Sudden onset
Evidence of arteriopathy - high BP, past strokes, focal neurology
What are the symptoms of Lewy Body dementia?
Fluctuating cognitive state
Hallucinations (visual)
Parkisonism
Don’t give anti-psychotics
What are the symptoms of fronto-temporal dementia?
Behaviour/personality change
- disinhibition, hyperorality, emotional unconcern
Memory and spatial orientation maintained until later stages
What is Pick’s disease?
Fronto-temporal dementia with Pick inclusion bodies (spherical clusters of tau laden neurons)
What is the pathology of dementia/AD?
APOE - main gene
- beta amyloid plaques
- tau tangles
What is the medical management of dementia/AD?
AChE-I
- Donepexil
- Rivastigmine
- Galantamine
Anti-glutamatergic (NMDA antagonist)
- Memantine
Anti-psychotics
- give for psychosis/extreme agitation
- DO NOT GIVE: PD, AD, Lewy body, vascular
Also refer to a memory service
BP control
What is the diagnostic triad of Parkinson’s?
Extrapyrimidal:
- tremor (at rest, ‘pill-rolling’)
- hypertonia (cogwheel rigidity)
- bradykinesia (slow movement initiation, decreasing movement amplitude)
What are the prodromal symptoms of PD?
Depression
Agnosia - loss of sense of smell
What are the symptoms of PD?
Autonomic dysfunction - postural hypoTN, constipation, urinary frequency Sleep disturbance Loss of smell Neuropsychiatric dysfunction - depression - dementia - psychosis
What are some PD plus syndromes?
Progressive supernuclear palsy
- postural instability, vertical gaze palsy, falls, speech and swallowing problems
Multiple system atrophy
- early autonomic features, postural hypoTN, cerebellar and pyrimidal signs, rigidity > tremor
Cortico-basal degeneration
- akinetic rigidity in one limb, cortical sensory loss, apraxia
How is PD managed?
Levodopa (in combination with a DDC)
- co-beneldopa
- co-careldopa
Can cause dyskinesia, dystonia, vomiting
Dopamine agonists
- Ropinirole, pramipexole
- Rotigotine patches
- Bromocriptine/cabergoline less favoured
What medical management can be added in later stage PD?
Amantadine (for drug induced dyskinesias)
Anticholinergics - benzhexol
MAO-B I - rasagiline, selegiline
COMT I - entacapone, tolcapone
What is the pathology of MS?
Inflammatory plaques of demyelination in the CNS
What are the symptoms of MS?
UL optic neuritis - pain when moving eyes and loss of central vision, diplopia, hemianopia
Pins and needles, loss of vibration sense, trigeminal neuralgia
Spastic weakness
ED, anorgasmia, urinary retention/incontinence
Trunk and limb ataxia, intention tremor, scanning speech
Cognitive decline
What might investigations show in MS?
MRI - demyelination
CSF - oligoclonal bands of IgG (not present in serum)
Delayed evoked potentials
How is MS managed?
Disease modifying drugs (relapsing remitting) - di-methyl fumarate (relapsing remitting), alemtuzumab (T cells)
Methylprednisolone (for a relapse)
Spasticity - gabapentin, baclofen
Tremor - botulinum
Urinary urgency/frequency - self-catheterisation, tolteridine
Fatigue - amantadine, CBT, exercise
What is the pathology of MND?
Loss of neurons in motor cortex, CN nuclei and anterior horn cells
NO sensory/sphincter problems
What are patterns of MND?
ALS - loss in motor cortex and anterior horns (UMN, LMN)
Bulbar palsy - loss in CN IX - XII (LMN in tongue)
Muscular atrophy - loss in anterior horn (LMN)
Primary lateral sclerosis - loss in motor cortex (UMN)
What are the symptoms of MND?
Stumbling, spastic gait Foot drop Proximal myopathy Weak grip Shoulder abduction (hard to wash hair)
UMN and LMN signs
What is the pathology of Myasthenia gravis?
Abs to nicotinic ACh receptors - post synaptic side
B and T cells involved
What are the symptoms of MG?
Increasing/relapsing muscular fatigue
- extraocular -> bulbar -> face -> neck -> limbs -> trunk
Symptoms worsen with exercise, gent, pregnancy, tetraciclines, quinine, b-blockers
Ptosis, diplopia, myasthenic snarl, eye ‘peek’ sign, voice fading
Normal reflexes
What do tests for MG show?
Abs - anti-AChR, MUSK abs
EMG - decremental muscle response to repeated stimulation
How is MG managed?
Anticholinesterase - pyridostigmine
Prednisolone (relapses)
Osteoporosis prophylaxis
Thymectomy (even without thymoma)
How is a myasthenic crisis managed?
Weakness of respiratory muscles
Treat cause, plasmapheresis (remove Ab), IVIg
What is the pathology of Lambert Eaton?
AI - Ab to voltage-gated Ca channels on presynaptic membrane
Paraneoplastic - small cell lung cancer
What are the symptoms of Lambert Eaton?
Gait difficulty (before eye signs unlike MG) Autonomic - dry mouth, constripation, impotence Hyporeflexia and weakness - improves after exercise
Diplopia and respiratory muscle involvement are rare
How is Lambert Eaton treated?
Pyridostigmine
3,4-diaminopyridine
IVIg
What is the pathology of GBS?
Acute inflammatory demyelinating polyneuropathy
Occurs a few weeks after infection - Abs attack nerves
What are the symptoms of GBS?
Rapid onset, proximal muscle involvement first, symmetrical
Sweating High pulse BP change Arrythmias CN involvement Mild sensory symptoms
How is GBS managed?
IV Ig
Plasma exchange
Do not give steroids
Complete paralysis can still have complete recovery
What is the pathology of Duchenne’s/Becker’s?
X-linked recessive
Dystrophin gene
What are the symptoms of Duchenne’s/Becker’s?
Onset at 4yo
Clumsy walking
Difficulty standing
Respiratory failure
Later onset and better outcomes in Becker’s
Very high CK levels
What is the pathology of myotonic dystrophy?
Autosomal dominant
Trinucleotide repeat expansions
What are the symptoms of myotonic dystrophy?
Hand/foot drop
Weak SCM
Myotonia
Facial weakness and wasting
What is the trinucleotide repeat in Huntingdon’s?
CAG
What are the symptoms of Huntingdon’s?
Middle age onset Depression Chorea Aggression Athetosis (abnormal muscle contraction)
What are the signs of neurofibromatosis 1 (NF1)
Cafe au lait spots Freckles Dermal neurofibromas Nodular neurofibromas Lisch nodules
What are the signs of NF2?
Bilateral acoustic neuromas (vestibular schwannomas)
Sensorineural hearing loss
Tinnitus
Vertigo
What is the trinucleotide repeat in Friedrich’s ataxia?
GAA in FXN gene
What is a Ddx of dementia?
Normal pressure hydrocephalus
- wet (incontinent)
- wacky (confused)
- wobbly
What is the trinucleotide repeat in Friedrich ataxia?
GAA
What is the trinucleotide repeat in myotonic dystrophy?
CTG
What is the trinucleotide repeat in fragile X syndrome?
CGG
