Neurodegenerative Diseases

Question 1

Define neurodegenerative disease

Answer 1

A progressive, irreversible condition leading to neuronal loss, usually due to accumulation of misfolded proteins which may be intracellular or extracellular

Question 2

Define dementia

Answer 2

A global impairment of cognitive function and personality without impairment of consciousness, beyond what might be expected from normal ageing, in more than one domain including memory

Question 3

Name the cognitive domains which can be affected by dementia

Answer 3

Memory, speech and language (aphasia), learned purposeful tasks (apraxia), object recognition (agnosia), executive function

Question 4

Name at least 4 neurodegenerative diseases caused by misfolded tau

Answer 4

Alzheimer’s disease, corticobasal degeneration, progressive supranuclear palsy, Pick’s disease, FTD-17

Question 5

Describe the macroscopic appearance of the brain in Alzheimer’s disease

Answer 5

Generalised atrophy, widened sulci, narrow gyri, enlarged ventricles - most marked in temporal and frontal lobes

Question 6

Describe the microscopic appearance of the brain in Alzheimer’s disease

Answer 6

Extracellular beta-amyloid plaques, intracellular neurofibrillary tau tangles, loss of cholinergic neurons, cerebral amyloid angiopathy

Question 7

Describe the management of Alzheimer’s disease

Answer 7

Anti-cholinesterases (e.g. donepezil, rivastigmine), glutamate antagonists (e.g. memantine), supportive (e.g. memory book)

Question 8

Describe the typical features of dementia with Lewy bodies

Answer 8

Day-to-day fluctuations in cognitive performance, visual hallucinations, spontaneous parkinsonism, recurrent falls, syncope

Question 9

Describe the pathology of Parkinson’s disease/ dementia with Lewy bodies

Answer 9

Loss of dopaminergic neurons in the substantia nigra with presence of Lewy bodies of abnormal alpha-synuclein, leading to decreased stimulation of the motor cortex by the basal ganglia

Question 10

Describe the main clinical features of Parkinson’s disease

Answer 10

Tremor, rigidity, akinesia, postural instability, neuropsychiatric symptoms, autonomic instability, sleep disorders

Question 11

Describe the main features of progressive supranuclear palsy

Answer 11

4R tauopathy causing supranuclear palsy, early (backwards) falls, axial rigidity, akinesia, dysarthria, and dysphagia

Question 12

Describe the main features of corticobasal syndrome

Answer 12

4R tauopathy classically causing unilateral parkinsonism, dystonia, apraxia, and alien limb phenomenon. May cause progressive non-fluent aphasia

Question 13

Describe the main features of multiple system atrophy

Answer 13

Alpha-synucleinopathy which can be predominantly cerebellar or predominantly parkinsonian. Associated with early autonomic dysfunction. Signs include tremor, squeaky hypophonia, dysrhythmia of rapid alternating movements, and hypermetria

Question 14

Describe the clinical features of multiple sclerosis

Answer 14

Presents at 20-40 with two lesions disseminated in time and space (e.g. optic neuritis, poor coordination). May be relapsing-remitting or primary progressive.

Question 15

Describe the histology of multiple sclerosis

Answer 15

Plaques showing sharp margins of myelin loss

Question 16

Name two proteins which may be targeted by autoantibodies in multiple sclerosis

Answer 16

Myelin basic protein, proteolipid protein

Question 17

Describe the macroscopic appearance of the brain in multiple system atrophy

Answer 17

Motor and premotor cortical atrophy, marked cerebellar atrophy, shrinkage of the middle cerebellar peduncle, pons, and inferior olivary nucleus, and pallor of the locus coeruleus and substantia nigra

Question 18

What is the microscopic difference between Parkinson’s disease and multiple system atrophy?

Answer 18

Parkinson’s disease has only neuronal involvement/ alpha-synuclein, multiple system atrophy has neuronal and glial inclusions