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Question 1

Nigrostriatal pathway

Answer 1

control of movement

affected in parkinson’s disease

Substantia nigra pars compacta > striatum

Question 2

Describe cortical input to the basal ganglia

Answer 2

Cortical inputs are excitatory (glutamate) for the medium spiny neurons in the striatum.

GPi, Substantia nigra pars reticulata are the same nucleus. The neurons are inhibitory (Gabaergic)

Question 3

Describe the circuit from GPI to motor output

Answer 3

GPi is inhibitory, it will release GABA onto the VA/VL of the thalamus

The thalamus is excitatory onto the primary motor cortex

Motor output.

Question 4

Subthalamus is activated, what does it do to the pathway?

Answer 4

Subthalamic nucleus excites GPi, causing inhibition of the cortex (and movement)

Lesions of the subthalamic nucleus produce too much movement (contralateral hemiballismus)

Question 5

What is the “Direct Pathway”

Answer 5

Cortex excites Striatum

Striatum increases inhibition of Gpi.

Disinhibition: Gpi decreases inhibition on thalamus

Thalamus increases excitatory output to primary motor cortex

Increased output

Question 6

What is the indirect pathway

Answer 6

Cortex releases excitatory input to striatum

Striatum is inhibitory for GPe! (inhibitory)

GPe decreases inhibition of subthalamic.

Subthalamic is more excitatory for GPi.

GPi increases inhibition of thalamus.

Thalamus decreases stimulation of motor cortex, decreases output.

Question 7

How does SNpc influence the direct?

Answer 7

Dopamine activates DA1 receptors on the striatum.

Striatum increases inhibitory output to Gpi, thereby increasing motor output.

Question 8

How does SNpc affect the indirect pathway

Answer 8

Dopamine activates DA2 receptors on the striatum.

This time it is inhibitory, so the striatum decreases inhibition of GPe.

GPe increases inhibition of the subthalamic

Subthalamic decreases stimulation of the Gpi

GPi decreases inhibition on the thalamus, increasing excitation of the cortex, increasing motor output.

Question 9

What is the role of ACh in striatum?

Answer 9

It will increase striatal output for both pathways.

However it will preferentially increase striatal output into the indirect pathway, increase inhibition of GPe.

This is why anticholinergics are used for parkinsons disorder

Question 10

Hemiballismus

Chorea

Athetosis

Answer 10

Hemiballismus:
• Spontaneous, involuntary movements
• Usually caused by lacunar infarcts in the subthalamic nucleus

Chorea:
• Nearly continuous rapid movements of face, tongue, or limbs.
• Most common in Huntington’s disease.

Athetosis:
• Slow, writhing movements, mostly in hands and fingers. Patients
cannot maintain a fixed position. Often in children with cerebral
hypoxia, affecting the basal ganglia.
(somewhere between chorea and posture instability)

Question 11

Hypokinesia

Rigidity

Answer 11

Hypokinesia – decreased amplitude of movements

Rigidity - described as “waxy” or “lead-pipe.”
May be “cogwheeling,” with regular interruptions.

Unlike spasticity, rigidity will resist the whole range of movement, and maybe push back at you.

Question 12

Dystonia

Answer 12

Dystonia
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Slower	than chorea,	 sustained contractions in twisting	postures 
-Triggered	by	voluntary	movements 
-Writer’s cramp	is most common 

Most cases are familial A causes:
• Genetic
• Focal lesions of basal ganglia
• Disorders of dopamine metabolism

Treatment:
• Botulinum toxin
• DBStimulation of the GP

Question 13

Tardive dyskinesia

Answer 13

abnormality or impairment of voluntary movement:
resulting from drugs that have dopaminergic actions

• antipsychotic drugs (traditional>atypical)
• anti-emetic drugs
• manganese
• these drugs decrease dopamine, this can lead to an upregulation of dopamine receptors and too much sensitivity to dopamine.

Can persist after discontinuation of drugs. Less of a problem with new anti-psychotics

Question 14

Parkinsons tremor vs Essential tremor

Answer 14

Parkinsons tremor:
(4-6 Hz at rest)

Hands and arms are more common, legs and mouth can also be affected 
-Begins unilaterally
-At rest 
-BG
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Essential tremor:
(6-8 Hz)

Hands, arms, head, face, legs, trunk 
Usually bilateral 
Increases with activity or posture 
-no other motor abnormalities. 
-Cerebellum

Question 15

Huntington Chorea

Answer 15

Autosomal dominant neurodegenerative disorder with cell loss in caudate and putamen
Also affects the cortex (mainly frontal and temporal)

Enkephalin-containing GABAergic cells affected in HD
> more inhibition of STN and increased movement.

Onset 40s and 50s. Progressive and neurodegenerative. Eventually leads to akinetic/rigid form of the disease
Median survival is 15 yrs due to respiratory complications.
Treatment: drugs that decrease dopamine

Major symptoms:

1. Chorea
2. Dementia

Psychiatric manifestations

• anxiety
• mood changes
• OCD
• impulsiveness
• cognitive impairment
• memory loss

Question 16

Parkinsons

Answer 16

Parkinsons

Clinical symptoms:

1. Bradykinesia: slowed movements
2. Resting tremor (pill rolling)
3. Rigidity: lead pipe through range of motion, or cog wheeling with regular jerking
4. Postural instability

(postural instability comes later in the disease)

Motor: 
masked facies (hypomimia) 
-loss of automaticity 
-stooped posture
-decreased arm swing
-difficulty rising from chair
-freezing
-*RETropulsion - take 2 steps back when pulled from behind (instead of 1 step) 

Non-motor

• loss of olfaction (hyposmia), very early sign.
• sleep problems
• personality changes
• pain
• urinary disturbances
• depression: MOST common psychiatric problem in PD.
• Dementia - dysexecutive syndrome, later in disease, no memory loss, loss of attention, loss of language fluency

Question 17

Histological marker of PD

Answer 17

Neurons in the SN of people with PD contain Lewy Bodies

Lewy Bodies are spherical masses within the cell body that contain abnormal aggregations of proteins: particularly alpha-synuclein, a cytosol protein found in many regions of the brain.
Alpha-synuclein is normally involved in vesicle transport.

Question 18

DBS and PD

Answer 18

the most common surgical approach to PD, thought to suppress excessive activity. For advanced and drug resistant PD.

GPi or subthalamic nucleus for PD symptoms (bradykinesia, rigidity, tremor)

VL for tremor predominant

Question 19

What are preclinical symptoms of parkinsons

Answer 19

1. Olfactory loss
2. Depression
3. Sleep abnormalities
4. Sympathetic denervation
5. Constipation
6. Genetic markers

Question 20

What are parkinsonism plus syndromes

Answer 20

Primary neurodegenerative syndromes that share characteristics of PD

• Lack of resting tremor
• symmetrical symptoms
• early postural instability
• lack of response to dopamine

Question 21

Progressive Supranuclear Palsy

Answer 21

• most common form of atypical parkinsonism
• neurodegenerative
• affects rostral midbrain
• symptoms begin after age 50
• differences from PD
• *decreased range of vertical eye movement (first sign)
• imbalance, falling, trunk rigidity (vs limbs in PD)
• swallowing changes
• Dementia progresses more rapidly

-some relief from dopaminergic therapies but not strong

Question 22

What side of the lesion are hypokinetic, hyperkinetic and dyskinesias found on?

Answer 22

The contralateral side.

Question 23

What is contralalteral hemiballismus?

Answer 23

Ballismus or ballism (called hemiballismus or hemiballism in its unilateral form) is a very rare movement disorder. It is a type of chorea caused in most cases by a decrease in activity of the subthalamic nucleus of the basal ganglia, resulting in the appearance of flailing, ballistic, undesired movements of the limbs.

Question 24

How does the Snpc play roles in indirect and direct pathways?

Answer 24

Dopamine always works on the striatum but

DA1: excitatory > increases striatal inhibitory output on Gpi

DA2: inhibitory > decreases striatal inhibitory output on Gpe > increases inhibition on subthalamic nuclei