Neurodegenerative conditions

Question 1

What are the symptoms of AD?

Answer 1

Progressive, global impairment

• cognition
• visuo-spatial skills
• memory
• verbal skills
• planning

Later: mood changes, depression, psychosis, behaviour changes, agnosis

Question 2

What are the symptoms of vascular dementia?

Answer 2

Cumulative effect of many small strokes
Sudden onset
Evidence of arteriopathy - high BP, past strokes, focal neurology

Question 3

What are the symptoms of Lewy Body dementia?

Answer 3

Fluctuating cognitive state
Hallucinations (visual)
Parkisonism

Don’t give anti-psychotics

Question 4

What are the symptoms of fronto-temporal dementia?

Answer 4

Behaviour/personality change
- disinhibition, hyperorality, emotional unconcern

Memory and spatial orientation maintained until later stages

Question 5

What is Pick’s disease?

Answer 5

Fronto-temporal dementia with Pick inclusion bodies (spherical clusters of tau laden neurons)

Question 6

What is the pathology of dementia/AD?

Answer 6

APOE - main gene

• beta amyloid plaques
• tau tangles

Question 7

What is the medical management of dementia/AD?

Answer 7

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

Question 8

What is the diagnostic triad of Parkinson’s?

Answer 8

Extrapyrimidal:

• tremor (at rest, ‘pill-rolling’)
• hypertonia (cogwheel rigidity)
• bradykinesia (slow movement initiation, decreasing movement amplitude)

Question 9

What are the prodromal symptoms of PD?

Answer 9

Depression

Agnosia - loss of sense of smell

Question 10

What are the symptoms of PD?

Answer 10

Autonomic dysfunction 
- postural hypoTN, constipation, urinary frequency
Sleep disturbance 
Loss of smell 
Neuropsychiatric dysfunction 
- depression
- dementia
-  psychosis

Question 11

What are some PD plus syndromes?

Answer 11

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

Question 12

How is PD managed?

Answer 12

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

Question 13

What medical management can be added in later stage PD?

Answer 13

Amantadine (for drug induced dyskinesias)

Anticholinergics - benzhexol
MAO-B I - rasagiline, selegiline
COMT I - entacapone, tolcapone

Question 14

What is the pathology of MS?

Answer 14

Inflammatory plaques of demyelination in the CNS

Question 15

What are the symptoms of MS?

Answer 15

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

Question 16

What might investigations show in MS?

Answer 16

MRI - demyelination
CSF - oligoclonal bands of IgG (not present in serum)
Delayed evoked potentials

Question 17

How is MS managed?

Answer 17

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

Question 18

What is the pathology of MND?

Answer 18

Loss of neurons in motor cortex, CN nuclei and anterior horn cells

NO sensory/sphincter problems

Question 19

What are patterns of MND?

Answer 19

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)

Question 20

What are the symptoms of MND?

Answer 20

Stumbling, spastic gait
Foot drop 
Proximal myopathy 
Weak grip 
Shoulder abduction (hard to wash hair)

UMN and LMN signs

Question 21

What is the pathology of Myasthenia gravis?

Answer 21

Abs to nicotinic ACh receptors - post synaptic side

B and T cells involved

Question 22

What are the symptoms of MG?

Answer 22

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

Question 23

What do tests for MG show?

Answer 23

Abs - anti-AChR, MUSK abs

EMG - decremental muscle response to repeated stimulation

Question 24

How is MG managed?

Answer 24

Anticholinesterase - pyridostigmine
Prednisolone (relapses)
Osteoporosis prophylaxis

Thymectomy (even without thymoma)

Question 25

How is a myasthenic crisis managed?

Answer 25

Weakness of respiratory muscles Treat cause, plasmapheresis (remove Ab), IVIg

Question 26

What is the pathology of Lambert Eaton?

Answer 26

AI - Ab to voltage-gated Ca channels on presynaptic membrane Paraneoplastic - small cell lung cancer

Question 27

What are the symptoms of Lambert Eaton?

Answer 27

``` 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

Question 28

How is Lambert Eaton treated?

Answer 28

Pyridostigmine 3,4-diaminopyridine IVIg

Question 29

What is the pathology of GBS?

Answer 29

Acute inflammatory demyelinating polyneuropathy | Occurs a few weeks after infection - Abs attack nerves

Question 30

What are the symptoms of GBS?

Answer 30

Rapid onset, proximal muscle involvement first, symmetrical ``` Sweating High pulse BP change Arrythmias CN involvement Mild sensory symptoms ```

Question 31

How is GBS managed?

Answer 31

IV Ig Plasma exchange Do not give steroids Complete paralysis can still have complete recovery

Question 32

What is the pathology of Duchenne's/Becker's?

Answer 32

X-linked recessive | Dystrophin gene

Question 33

What are the symptoms of Duchenne's/Becker's?

Answer 33

Onset at 4yo Clumsy walking Difficulty standing Respiratory failure Later onset and better outcomes in Becker's Very high CK levels

Question 34

What is the pathology of myotonic dystrophy?

Answer 34

Autosomal dominant | Trinucleotide repeat expansions

Question 35

What are the symptoms of myotonic dystrophy?

Answer 35

Hand/foot drop Weak SCM Myotonia Facial weakness and wasting

Question 36

What is the trinucleotide repeat in Huntingdon's?

Answer 36

CAG

Question 37

What are the symptoms of Huntingdon's?

Answer 37

``` Middle age onset Depression Chorea Aggression Athetosis (abnormal muscle contraction) ```

Question 38

What are the signs of neurofibromatosis 1 (NF1)

Answer 38

``` Cafe au lait spots Freckles Dermal neurofibromas Nodular neurofibromas Lisch nodules ```

Question 39

What are the signs of NF2?

Answer 39

Bilateral acoustic neuromas (vestibular schwannomas) Sensorineural hearing loss Tinnitus Vertigo

Question 40

What is the trinucleotide repeat in Friedrich's ataxia?

Answer 40

GAA in FXN gene

Question 41

What is a Ddx of dementia?

Answer 41

Normal pressure hydrocephalus - wet (incontinent) - wacky (confused) - wobbly

Question 42

What is the trinucleotide repeat in Friedrich ataxia?

Answer 42

GAA

Question 43

What is the trinucleotide repeat in myotonic dystrophy?

Answer 43

CTG

Question 44

What is the trinucleotide repeat in fragile X syndrome?

Answer 44

CGG