Lecture 23

Question 1

How are diseases of the brain traditionally divided into?

Answer 1

Neurological (physical) signs + symptoms

Psychiatric (mental) disorders

Question 2

What do general neurological assessment of patients include?

Answer 2

State of consciousness
Mental state, attitude, insight
Cognitive function - how well you think
e.g. problem solving questions
Gait - the way you walk
e.g. look for paralysis (peripheral damage), cerebellar dysfunction can cause stomping
Coordination and fine movements
- can be affected by neurotransmitter problems
Cranial nerves
Motor systems - (wasting, tremor, power, tone, reflexes)
Sensory systems - (vibration, touch, pain, 2 point discrimination)

Question 3

What do general psychiatric assessment include?

Answer 3

Appearance and general behavior
Mood and affect
Speech - disorders of thought (stream, form, content)
Insight
Abnormal beliefs (e.g. delusions), and perceptions (e.g.hallucinations)
Cognitive state - concentration, confusion, memory

Question 4

What are the symptoms of Parkinson’s disease?

Answer 4

Decrease in spontaneous movements
Gait difficulty 
Postural instability
Rigidity and tremor
 - can get worse under stress

Question 5

What is the pathology of Parkinson’s disease?

Answer 5

Degeneration of the pigmented neurons in the substantia nigra of the brain, resulting in decreasing dopamine availability

Question 6

What is the incidence of Parkinson’s disease?

Answer 6

1-2% frequency increases exponentially 60 uears
- mortality between 45 and 100 is 7%
- men and women equally affected
- -potentially that is a disease of aging
Higher incidence in developed countries
- more people are looking for it and there may be more people in developing countries than found currently
- could be due to shorter life span

Question 7

What does the lack of dopamine suggest?

Answer 7

abnormal metabolism

Question 8

What is the direct pathway in the basal ganglia circuit?

Answer 8

Outflow from the striatum indirectly inhibits GPi and SNr. Striatal neurons containing D1 receptors constitute the direct pathway and project to the GPi/SNr

Question 9

What is the indirect pathway in the basal ganglia circuit?

Answer 9

Comprises inhibitory connections between the striatum and the GPe and between the GPe and the STN. Striatal neurons containing D2 receptors are part of the indirect pathway and project to the GP3

Question 10

What influence does the STN exert?

Answer 10

Excitatory in GPi and SNr

Question 11

What does GPi/SNr output to?

Answer 11

Inhibitory

Ventral lateral nucleus (VL) of the thalamus

Question 12

Where is dopamine released from?

Answer 12

Nigrostriatal (SNc) neurons to activate the direct and inhibit the indirect pathwy

Question 13

What suppresses movement in Parkinson’s disease?

Answer 13

Increased inhibition of the thalamocortical pathway

Question 14

What suppresses movement in the direct pathway?

Answer 14

Decreased striatal dopamine stimulation causes decreases inhibition of the GPi/SNr

Question 15

What suppresses movement in the indirect pathway?

Answer 15

Decreased dopamine inhibition causes increased inhibition of the GPe, resulting in disinhibition of the STN. Increased STN output increases GPi/SNr inhibitory output to the thalamus

Question 16

In Parkinson’s disease, what does decreased striatal dopamine cause?

Answer 16

Increased inhibitory output from GPi/SNr

Question 17

What is the pathology of the disease is characterized by?

Answer 17

the accumulation of a protein called alpha-synuclei into inclusion called Lewy bodies in neurons, and from insufficient formation and activity of dopamine produced in certain neurons of parts of the midbrain

Question 18

What is the most effective site for deep brain stimulation?

Answer 18

STN

Question 19

What frequency alleviates symptoms of Parkinson’s and what frequency worsens symptoms?

Answer 19

Over 60Hz

Under 30Hz

Question 20

what is the hypothesis for deep brain stimulation?

Answer 20

Stimulation prevents low frequency rhythm generation and desynchronises the extrastriatal basal ganglia and cortex

Question 21

What are modern treatments for Parkinson’s disease?

Answer 21

Protection:
Ca voltage channel blockers (SN cells have high energy Ca burden?), glial derived neurotrophic factor (amgen)
Overstimulation of Ca channel causes problems in dopamine production
Regeneration:
Transplantation, stem cells (induced, embryonic)
Stimulation:
Smart stimulators, optogenetics

Question 22

What is optogenetics?

Answer 22

Flash a light on genes to activate it

Question 23

What are the symptoms of Huntington’s disease?

Answer 23

Progressive hyper/dyskinesias followed by akinesia and dystonia and dementia/psychoses

Question 24

What is the pathology of Huntington’s disease?

Answer 24

Striato-GPe neurons die first, followed by striato-GPi neurons and finally more widespread neurodegeneration
Associated with nuclear and cytoplasmic inclusions containing mutant huntingtin and other proteins

Question 25

What is the incidence of Huntington’s disease?

Answer 25

Rare; 0.04 - 0.1 %

Question 26

What is Huntingtin important for?

Answer 26

Synaptic vesicle dynamics and transmitter release

Question 27

What are Basal ganglia circuitry changes in huntington’s?

Answer 27

Striatum to GPe (GABA)
Straitum to SNr/GPi (GABA)
Animal models suggest that cortical dysfunction is the initial trigger in huntington’s disease