Neuropathology 2

Question 1

what are the problems of

Answer 1

• Sampling error
• Accessibility of tissue
• Often tissue only available late in disease process (i.e. post- mortem)

Question 2

• Amyotrophic lateral sclerosis (ALS)

Answer 2

brisk reflexes AND fasciculations!

most commonest type of MND

begins with cramps and weakness on one side followed by progression to the same area on the other side

patients often die due to the disease progressing to the respiration centres

genetic mutation in the super oxide dismutase

Question 3

• primary lateral sclerosis

Answer 3

affects Upper MNs predominantly

Question 4

• spinal muscular atrophy

Answer 4

affects lower motor neurons predominantly

Question 5

UMN cell bodies are

Answer 5

in brain or brainstem and do not project outside the CNS

Question 6

LMN cell bodies are in

Answer 6

brainstem or spinal cord and project outside the CNS to muscle

Question 7

common characterisation of ALS

Answer 7

• focal weakness and clumsiness which spreads
• painful fasciculation and cramping
• dysarthria, dysphagia or respiratory issues
• upper and lower motor neurone signs

EMG would revel evidence of denervation and re-innervation in two extremities or body segments, arm and trunk or leg and head etc.

Question 8

which nuclei are effects by ALS

Answer 8

brainstem nuclei hypoglossal nuclei

Question 9

dementia key points to remember

Answer 9

• is a syndrome not a disease
• pathology post mortem is ultimately the only definitive diagnostic test
• no single reliable biomarker
• treatments work better the longer they are used

Question 10

what are the different types of dementia

Answer 10

• Alzheimer’s Disease 65%
• Dementia with Lewy Bodies 20%
• Vascular Dementia 10%
• Frontotemporal dementias 5%

Question 11

Alzheimer’s disease pathology

Answer 11

• Reducedbrainweight
• Cortical atrophy (reduced thickness)
• Enlarged ventricles
• Cell loss evident in medial temporal lobes and hippocampi

Question 12

Microscopic Pathological features of Alzheimers dementia

Answer 12

Neurofibrillary Tangles (NFTs) - these are not unique to AD

• predominantly composed of tau
• normal tau stabilises axons
• In AD tau is hyperphosphorylated in tangles and forms paired helical filaments in cytoplasm

Question 13

amyloid plaques

Answer 13

• Extracellular insoluable proteinaceous deposits

* Largely composed of Amyloid β peptides (Aβ peptides)

Question 14

diffuse plaque

Answer 14

often found in older people with no dementia

Question 15

neuritic plaque

Answer 15

surrounded bu thick distorted neuronal processes

strongly associated with cognitive decline

Question 16

parkinsons pathology

Answer 16

repetitive pill rolling movements

persistent tremors

shuffling gait, taking small steps

Question 17

• PD is characterised by:

Answer 17

• neuronal loss in the substantia nigra
• degeneration of the nigrostriatal tract
• profound loss of dopamine in the Basal nuclei (less than 20%
of normal)

Question 18

Lewy

bodies

Answer 18

Surviving nigral neurons contain these,

They can be stained with antibodies to alpha- synuclein

Question 19

Prion diseases in spongiform encephalopathies

Answer 19

Caused by a misfolded cell surface protein – causes cells and proteins to clump together resulting in cell death
Most common human form is CJD (Creutzfeldt-Jakob disease)

Varient CJD communicable by ingestion of meat infected with ‘mad cow disease’

Question 20

Symptoms of CJD

Answer 20

Rapidly developing dementia – key trigger for investigation (MRI, Biopsy) •Difficulty walking – needing a cane or frame
•Muscle stiffness and fatigue
•Speech problems
In later the stages patients can suffer from
•Hallucinations •Confusion

Question 21

CNS inflammation – Multiple Sclerosis

Answer 21

• Immune cells are stimulated to phagocytose the Myelin normally found insulating the axons of
nerve cells
• Where axon insulation is removed, the signal transmission along the fibre slows, and within a
pathway can become delayed
• Proprioceptive and other feedback systems do not then synchronise well with motor output
• Muscles fatigue and patients find it difficult to control movement properly

Question 22

Peripheral Neuropathy causes

Answer 22

• Diabetes Mellitus
• Idiopathic (cause unknown)
• Toxic – alcohol, drugs
• Vitamin Deficiency (B12)
• Post-infectious (Guillain-Barre syndrome)
• Paraneoplastic (T-cell autoimmune response)
• Leprosy
• Amyloid, other inflammation (e.g. vasculitis)

Question 23

Charcot- Marie-Tooth

Answer 23

Inherited Peripheral Neuropathy

Loss of distal motor and sensation with associated muscle wasting and weakness

‘peripheral myelin P22’ gene

Question 24

Sural nerve biopsy

Answer 24

loss sensation, 30% pain

Question 25

• Slow twitch (I) fibers innervated by

Answer 25

alpha 2 motor neurons, smaller of the two α motor neurons

Question 26

• Fast twitch (II) fibers innervated by

Answer 26

alpha 1 motor neurons, larger of the two α motor neurons

have higher excitation threshold and faster conduction velocity

Question 27

Motor Unit Recruitment

Answer 27

• Motor neurons recruited in order of size: Size Principle
• Smallest alpha motor neurons, α2, which belong to slow twitch recruited first
• Largest alpha motor neurons, α1, which belong to fast twitch recruited last

Question 28

Muscle Fibre Staining Properties

Answer 28

• Slow twitch (type I) have myosin isoforms with low ATPase activity.
• Fast twitch (type II) have myosin isoforms with high ATPase activity that promotes rapid breakdown of ATP for energy of high-speed muscle shortening.

Question 29

ST distribution

Answer 29

• Most individuals possess between 45 and 55% ST

Question 30

Muscle biopsy

Answer 30

• Usually done under LA
• Usually deltoid, quadriceps or tibialis anterior (often muscle & nerve) • Way of dealing with biopsy depends on what you’re looking for.
• Usually have done CPK and EMG first