Movement disorders

Question 1

What are movement disorders

Answer 1

group of nervous system diseases mainly manifested by motor symptoms such as voluntary movement delay, involuntary movement, abnormal muscle tone, postural and gait disorders, and mostly related to basal nucleus or basal ganglia lesions

Question 2

What is the basal nucleus

Answer 2

is a group of grey matter nuclei in the subcortex, composed of caudate nucleus, putamen, globus pallidus, subthalamic nucleus and substantia nigra.
In higher animals, the basal nucleus regulates motor functions; mainly through the connections between the cerebral cortex- basal nucleus- thalamus- cerebral cortex or cortio-basal ganglia-thalamo-cortical loop

Question 3

Provide a description of the basal ganglia

Answer 3

consists of 5 pairs of nuclei: caudate nucleus, putamen, globus pallidus, subthalamic nucleus and substantia nigra

Question 4

What is the striatum

Answer 4

Part of basal ganglia
- consists of dorsal striatum: caudate nucleus
and ventricular striatum: nucleus accumbens and olfactory tubercle

Question 5

What is the globus pallidus

Answer 5

• part of basal ganglia
  consists of an internal segement (GPi) and external segment (GPe)

Question 6

What is the substantia nigra

Answer 6

• part of basal ganglia
  Striatal dopaminergic pathological changes in pathway will lead to increased output of basal nucleus and excessive inhibition of cortical motor function, resulting in parkinsonism, which is mainly characterised by rigidity and hypokinesia

Question 7

What can striatum and subthalamic nucleus lesions lead to

Answer 7

lead to decreased output of basal nucleus and excessively facilitated cortical motor function, leading to chorea as main manifestation

Question 8

What is done during surgical treatment of parkinsons disease

Answer 8

One side of subthalamic nucleus of medial globua pallidus is damaged –> applying high frequency electrical stimulation to these two nuclei can alleviate contralaateral symptoms of parkinsons disease which may be to correct abnormal output of basal nucleus

Question 9

What are the main mainfestations of parkinsonism disease

Answer 9

resting tremors, rigidity, bradykinesia and postural instability

Question 10

What is the etiology and pathogenesis of parkinsons disease

Answer 10

degeneration and death of substantia nigra dopaminergic neuron
(multi-factorial)

Question 11

Which genes are associated with PD

Answer 11

Familial cases: LRRK2, PARK7, PINK1, PRKN, or SNCA gene

Question 12

For the pathology of PD, what basic lesions can be seen

Answer 12

• dopaminergic neurons and other pigment containing neurons in the substantia nigra compact area are degenerated and lost
• loss of pigmentation in substantia nigra is contrasted with a normal midbrain that still has dark pigmentation in the region of the substantia nigra above the cerebral peduncles
• eosinophilic inclusion bodies appear in cytoplasm of remaining neurons –> Lewy bodies

Question 13

For pathology PD, what biochemical changes can be seen

Answer 13

• due to significant degeneration and loss of strong dopaminergic neurons in patient with PD, substantia nigra striatal dopaminergic pathway changes
• levels of dopamine transmitters in striatum is significantly reduced
• <70-80%: clinical symptoms of dopamine transmitter decrease will appear
• the functions of 2 major transmitter systems, dopamine and ACh in striatum oppose each other, and the balance between the two plays an important role in regulating the motor function of basal nucleus
• striatal dopamine levels are significanlty reduced –> hyperactive ACh system, this transmitter imbalance is closely related to disturbance of cortical basal nucleus thalamus-cortical circuit, the increase in muscle tone and the reduction of movement
• the significant reduction of dopamine levels in the midbrain limbic system and midbrain cortex system is biochemical basis of high-level neural activity abnormailities such as mental decline and mood disorders

Question 14

What are the clinical manifestations of PD

Answer 14

average age of onset is about 55 years old. it is more common after 60 years of age, before the age of 40 is relatively rare for men to have isidious onset and slow progress
Motor symptoms:
- static tremor
- rigidity
- bradykinesia
- postural instability
Non-motor symptoms:
- cognitive dysfunction and dementia
- psychosis and hallucinations
- sleep disturbances
- fatugue
- autonomic/olfactory/GI dysfunction
- pain and sensory disturbances

Question 15

Ancillary tests for PD

Answer 15

• routine examinations of blood, salvia and brain fluid are normal
• structural images such as CT and MRI have no characteristuc changes
• molecular imaging PET or SPECT can show abnormalities in early stage of disease or even in subclinical stage and has a high diagnostic value. Dopamine transporter function imaging can also show a significant decrease

Question 16

How is PD diagnosed

Answer 16

• based on distinctive clinical feature discerned from history and neurologic examination (bradykinesia plus temor/rigidity must be present)

Question 17

Differential diagnosis for PD

Answer 17

• essential tremor
• dementia with Lewy bodies
• multiple system atropy
• cortico-basal degeneration
• progressive supranuclear palsy
• huntington disease
• secondary parkinsonism

Question 18

What are the 4 main anti-parkinson drugs used for treatment of PD

Answer 18

1. Monoamine oxidase type B (MAO B) inhibitors
2. Amantadine
3. Dopamine agonists (Das)
4. Levadopa

• Anti-cholinergic drugs have some anti-tremor activity