Disorders of the Basal Ganglia

Question 1

What are the components of the basal ganglia (aka extrapyramidal system)?

Answer 1

1. Striatum (caudate and putamen)
2. Globus pallidus
3. Substantia nigra
4. Subthalamic nucleus

Question 2

Pathogenesis of Parkinson’s disease?

Answer 2

Progressive loss of dopaminergic neurons in the substantia nigra -> decreased “direct pathway” inhibition -+ increased “indirect pathway” stimulation of the medial globus pallidus -> net increased inhibitory output of the GPm to the ventrolateral thalamic motor nuclei -> reduced stimulation of the motor cortex -> slow or absent clinical movements

Question 3

Pathogenesis of hyperkinetic disorders?

Answer 3

Net decrease of GPm output -> reduced inhibition of VL motor nucleus -> greater stimulation of motor cortex -> excessive motor activity

Question 4

Pathogenesis of hemiballismus?

Answer 4

Destruction of the subthalamic nucleus

Question 5

Pathogenesis of Huntington’s disease?

Answer 5

Loss of “indirect pathway” putaminal neurons to the lateral GP (inhibitory) -> increased inhibition of STN -> inhibition of GPm -> decreased inhibition of VL -> increased motor activity

Question 6

DDx - basal ganglia lesions?

Answer 6

Ischemic infarction, hemorrhage, tumor in the striatum or subthalamic nucleus -> contralateral choreoathetosis or hemiblassimus

Degenerative disorders (Huntington’s, Parkinson’s)

Question 7

Etiologies of parkinsonism?

Answer 7

Dopamine antagonist medication
Toxic exposure to manganese or carbon dioxide
Multiple ischemic infarctions of the basal ganglia
Parkinson’s

Question 8

Most common cause of parkinsonism?

Answer 8

Parkinson’s disease

Question 9

Primary clinical signs of Parkinson’s disease?

Answer 9

Resting tremor
Rigidity
Bradykinesia
Impaired postural reflexes

Question 10

Features of the resting tremor seen in Parkinson’s?

Answer 10

Prominent when sitting/reclining
Most often involving the distal upper limbs asymmetrically, sometimes the chin or lower limbs
Worse with stress
May accompany volitional movements such as waling
Pill-rolling
Begins on one side of the body, predominate on that side even when it spreads

Question 11

Features of the rigidity seen in Parkinson’s disease?

Answer 11

Stiffness or weakness
Constant resistance or increased tone when passively moving the affected limb (cogwheeling)
May not naturally swing when walking
Begins on one side of the body, predominates on that side even when it spreads

Question 12

Features of the bradykinesia seen in Parkinson’s disease?

Answer 12

Slowness or lack of movement
Patient may rock several times to rise off a chair and then slowly shuffle across the room with stooped posture
Need to take multiple small steps to turn around
Patient may “freeze” the feet to the floor
Manual tasks are slowed and clumsy
Automatic movements like blinking occur at slower rates, unconscious swallowing of secretions is inadequate -> drooling

Question 13

Features of impaired postural reflexes in Parkinson’s?

Answer 13

Balance instability while standing or walking, often out of proportion to the degree of rigidity

Question 14

Secondary signs of Parkinson’s?

Answer 14

Masked facies (lack of subtle facial movements)
Hypophonic speech (hoarse, soft, difficult to understand)
Micrographia
Involvement of the ANS -> severe constipation, bladder dysfunction, orthostatic hypotension
REM behavior sleep disorder

Question 15

Dx Parkinson’s?

Answer 15

Clinical: eliminate other causes, at least 2 of the 4 primary clinical signs should be present, and atypical features should be absent
Virtually all show some improvement with dopaminergic medication

Question 16

Pathologic hallmark of Parkinson’s?

Answer 16

Loss of the pigmented dopaminergic neurons in the substantia nigra, many of which have alpha-synuclein positive, eosinophilic, cytoplasmic inclusions called Lewy bodies

Question 17

Rx Parkinson’s disease?

Answer 17

L-dopa - most effective, combined with carbidoba (limits peripheral catabolism of L-dopa before it enters the brain)

Can further increase levels of L-dopa with COMT inhibitor (entacapone, etc.)

MOA type B inhibitor (selegiline) - extends benefits of dopamine

Dopamine agonists (ropinirole, pramipexole) - may reduce the longer term side effects of dyskinesia

Pallidotomy if severe

Deep brain stimulation to the subthalamic nucleus

Question 18

Presentation of Huntington’s disease?

Answer 18

35-40 years of age (early motor symptoms)
Choreoathetosis
Dementia
Behavioral syndromes (depression, anxiety, agitation, moodiness)

Question 19

Pathogenesis of Huntington’s?

Answer 19

AD degenerative disease

Question 20

Dx Huntington’s?

Answer 20

Blood test demonstrating multiple trinucleotide repeats in the huntingtin gene on chromosome 4

Question 21

Pathologic findings of Huntington’s?

Answer 21

Atrophy of the caudate nuclei (readily detected on MRI or CT if advanced -> frontal horns of the lateral ventricles appear relatively enlarged)

Question 22

Rx Huntington’s?

Answer 22

Dopamine antagonists help lessen the choreoathetosis, manage psychiatric symptoms

Tetrabenazine (catecholamine depleter)

Antidepressants - high rate of suicide