Neuropathology 2

Question 1

Describe the pathophysiology of ALS

Answer 1

• LMNs affected in bulbar and spinal locations

* UMNs affected in Brain, brainstem and spinal cord locations (less in extraocular area)

Question 2

Describe the potential causes of ALS

Answer 2

• most are sporadic
• abou 10% genetic from defective Super Oxide Dismutase which results in increase reactive O2 species forming causing cell death

Question 3

Describe the common signs of ALS

Answer 3

• focal weakness and clumsiness that spreads
• painful fasciculation and cramping
• possible dysarthria, dysphasia or resp issues
• UMN and LMN signs
• EMG showing denervation and reinnervation in 2 extremities

Question 4

What are the different types of dementia?

Answer 4

• Alzheimer’s Disease (65%)
• LBD (20%)
• vascular dementia (10%)
• frontotemporal dementia (5%)

Question 5

Describe the pathology of Alzheimer’s Disease

Answer 5

• reduced Brain weight
• cortical atrophy
• enlarged ventricles
• cell loss in medial temporal lobes and hippocampus

Question 6

Describe the microscopic pathological features in Alzheimer’s Disease

Answer 6

• NFT made of hyperphosphorylated helical filaments of tau (usually responsible for stabilising axons)
• neuritic amyloid plaques (of A-beta peptides) surrounded by thick distorted neuronal processes - associated with cognitive decline

Question 7

Describe the pathology of Parkinson’s Disease

Answer 7

• neuronal loss in substantia nigra - what’s left contains Lewy bodies
• degeneration in nigrostriatal tract
• loss of dopamine in basal nuclei

Question 8

What are the symptoms of CJD?

Answer 8

• rapidly developing dementia
• difficulty walking
• muscle fatigue and stiffness
• speech problems

Later:
* hallucinations and confusion

Question 9

Describe the pathophysiology of MS

Answer 9

• immune cells stimulated to phagocytose normal myelin found along axons of nerves
• this slows conduction resulting in delays along the pathway
• this results in desynchronisation between these motor delays and proprioception and feedback systems
• causes muscle fatigue and difficulty controlling movement

Question 10

What radiological sign can be used to aid an MS diagnosis?

Answer 10

• ‘Dawson’s fingers’ lesion - sign of demyelination

* found on the ventricles or fluid filled spaces in the Brain

Question 11

What histopathological feature is significant in MS?

Answer 11

• black staining reveals overgrown astrocyte mats

* sign of recurrent inflammation which also interferes with re-myelination

Question 12

List the causes of peripheral neuropathy

Answer 12

• diabetes mellitus
• idiopathic
• toxic - alcohol/drugs
• vitamin B12 deficiency
• post infection (Guillain- Barre Syndrome)
• paraneoplastic (consequence of cancer) - T-cell autoimmune response
• leprosy
• amyloid/other inflammation (eg. Vasculitis)

Question 13

What is a possible diagnostic procedure of peripheral neuropathy and some of the consequences associated with it?

Answer 13

• Sural nerve biopsy (nerve responsible for sensation to distal ankle and foot)
• some patients report reduced/loss of sensation in area distributed by sural nerve
• some report increase in pain

Question 14

Describe the contractile properties of muscle fibres

Answer 14

• slow twitch (I) innervated by smaller alpha 2 neurons
• fast twitch (II) innervated by larger alpha 1 neurons (higher excitation threshold and conduction velocity)
• neurons are recruited in order of size

Question 15

Describe how muscle biopsies are performed

Answer 15

• LA used on deltoid, quadriceps or tibialis anterior

* CPK (test for muscular dystrophy) and EMG (tests muscle innervation) usually done first

Question 16

List the types of inherited muscle diseases

Answer 16

• dystrophies
• congenital myopathies
• mitochondrial maternal line
• metabolic
• myotonic

Question 17

List the types of acquired muscle diseases

Answer 17

• inflammatory
• metabolic
• toxic
• disuse atrophy
• rhabdomyolysis (breakdown of skeletal muscle)