1) The basal ganglia are a group of subcortical nuclei that play an important role in motor control and learning. Dysfunction of the basal ganglia can result in movement disorders. 2) Parkinson's disease is a common hypokinetic movement disorder caused by degeneration of dopaminergic neurons in the substantia nigra. Symptoms include tremors, rigidity, bradykinesia, and postural instability. 3) Essential tremor is characterized by a bilateral postural or action tremor of the hands and arms and has a strong genetic component. Sydenham chorea is an acquired chorea associated with rheumatic fever.

1. MOVEMENT DISORDERS
Sisay Gizaw Geberemichael, M.D
Addis Ababa University, School of Medicine, Department of Neurology
Year -III Introductory Lecture

2. LECTURE OBJECTIVES
1) Illustrate basal ganglia anatomy
2) Overview of basal ganglia dysfunction
3) Overview of common diseases of basal ganglia

3. BASAL GANGLIA ANATOMY

4. Basal ganglia anatomy…
• What do you understand by the terms
pyramidal, extrapyramidal & basal ganglia?
• Motor systems:
1. Pyramidal (primary motor cortex)
2. Non-pyramidal
• Basal ganglia
• Cerebellum
• Others (brainstem nuclei, etc…)
Subcortical motor
systems

5. Basal ganglia anatomy…
• Components of basal ganglia (or nuclei):
1. Caudate
2. Putamen
3. Globus pallidus (GP)
• Interna (GPi) & externa (GPe)
4. Substantia nigra
• Pars compacta (SNc) & reticularis (SNr)
5. Subthalamic nucleus (STN)
6. Other (not important): nucleus accumbens
etc…
neostriatum
Lentiform
nucleus
Corpus
striatum

7. 3. Globus pallidus
1. Caudate nucleus (head)
2. Putamen
1
2
3
1
2
3
Thalamus
Internal capsule

8. Cerebral peduncle

9. EXTRAPYRAMIDAL MOTOR SYSTEM
DYSFUNCTIONS

10. Extrapyramidal dysfunctions…
MOTOR LOOPS:
• Cortex
• Subcortex
• Cortex
• Spinal cord
Cerebral cortex
cerebellum
Spinal cord
Basal ganglia
Feedback
1. Muscles
2. Sensory

11. Prefrontal
Other cortical
areas
M1
M2
Caudate &
putamen
VLo
Distal Limbs
"Basal Ganglia
Motor Loop"
VlLo =Ventrolateral nucleus, oralis (thalamus) M1=Primary motor cortex M2= supplementary motor cortex
Substantia
nigra
Glutamate
(+)
Dopamine (+/-)

12. Caudate &
putamen
Subthalamic
nucleus
Thalamus
Globus pallidus
externa (GPe)
Globus pallidus
interna (GPi)
Caudate &
putamen
Cortex
Globus pallidus
interna (GPi)
GABA (-)
GABA(-)
GABA(-)
GABA
Glutamate (+)
Glutamate (+)
Direct loop: excitatory
Pathways from the striatum to the thalamus
Indirect loop: inhibitory
Dopamine(-)

13. Prefrontal PPC
M1
M2
Cerebellum
Pons
VLc
Distal Limbs
"Lateral
Cerebellar
Motor Loop"
VLc=Vetrolteral nucleus, caudalis (thalamus)

14. Extrapyramidal dysfunctions…
Functions:
• Basal ganglia
– Motor
• Selection/ initiation
• Control slow mov't
• Tone-posture
– Non-motor:
• Emotion, cognition &
oculomotor function
• Cerebellum
– Motor
• Coordinate
• Learning
• Tone-posture
– Non-motor

15. Extrapyramidal dysfunctions…
• Effects of dysfunction in general:
1. Involuntary (excessive) movement
2. Altered movement (poverty of movement)
a. Slow
b. Interrupted
c. Uncoordinated
3. Altered posture & tone
4. Non-motor features
Hyperkinetic movement disorders
Hypokinetic movement disorders

17. Extrapyramidal dysfunctions…
• Parkinsonism:
– Causes:
• Idiopathic PD
• Neurodegenerative disorders
• Secondary parkinsonism
– Combinations of:
• Tremor (resting)
• Bradykinesia
• Rigidity
• Postural instability

18. Extrapyramidal dysfunctions…
• Tremor:
– Rhythmic & oscillatory mov't of body part,
constant frequency & variable amplitude
– Static
• Rest: parkinsonism & rubral
• Postural : physiological, essential & neuropathic
– Kinetic
• Action: physiological & essential
• Intention: cerebellar & rubral
– Psychogenic

19. Extrapyramidal dysfunctions…
• Chorea:
– Causes:
• Developmental/aging
• Hereditary
• Secondary
– Drugs, toxins, metabolic, infectious etc…
– Continuous, unsustained, rapid,
abrupt, and random muscle
contraction
• Hypotonia may occur

20. Extrapyramidal dysfunctions…
• Athetosis:
– Continuous, sinuous & nonpatterned writhing mov't
('slow chorea'), mainly due to cerebral palsy
• "Without fixed position”
• Ballismus:
– Sever, coarse chorea, usually unilateral
• Hemi- or biballismus
– Lesion of contralateral subthalamic nucleus &
adjacent structures (stroke usually)

21. Extrapyramidal dysfunctions…
• Dystonia:
– Causes:
• Primary
• Secondary
• Psychogenic
– Repetitive, patterned, twisting &
sustained mov't (slow athetotic or rapid)
• Focal
• Segmental
• Generalized

22. Extrapyramidal dysfunctions…
• Myoclonus:
– Simple brief jerk-like mov't, not
coordinated or suppressible
• Segmental
• Generalized
– Causes:
• Physiological
• Pathological
– Essential
– Epileptic
– Symptomatic
– Seg 6.flv

23. Extrapyramidal dysfunctions…
• Tics:
– Sudden, brief intermittent mov't
(motor tics) or utterance (vocal ticks)
• Cease during sleep & partially suppressible
– Causes:
• Physiological (mannerism)
• Primary (transient or persistent)
• Secondary
– Drugs, autoimmune/ postinfectious, etc….
– Seg 7.flv

24. Extrapyramidal dysfunctions…
• Diagnostic evaluation:
– History
– Physical examination
– Laboratory studies
• Routine
• Optional

25. COMMON DISEASES OF THE BASAL GANGLIA
(MOVEMENT DISORDERS)

26. ….diseases of basal ganglia
• Common movement disorders:
– Parkinson's disease (PD)
– Essential tremor (ET)
– Sydenham chorea (SC)
– Tardive dyskinesia (TD)

27. ….diseases of basal ganglia
• Parkinson's disease
– Archetype of hypokinetic movement disorders
• 1-2% of population over 50yrs
• M: F=1:1
• Median age=57yr (rare <50yrs)
– Motor features
• Hypokinesia, rigidity, tremor, gait & postural disturbances
– Non-motor features
• Autonomic, sleep disorders, psychiatric & cognitive
abnormalities

28. Reminiscent of PD

29. Parkinson's disease pathophysiology
(nigrostriatal neurons death)
Cortex (SMA)
Putamen/caudate
Substantia nigra (SNc)
VLo(thalamus)
Subthalamic nucleus
Globus pallidus (GPi)
+ Glu
+
Glu
+ D
+ Glu
+ Glu _ GABA
_
GABA
X
Dopaminergic < cholinergic effect

30. ….diseases of basal ganglia
• Diagnosis
– Clinical (rarely neuroimaging required)
• PD treatment:
– Medical (pharmacological)
– Surgical (pallidoectomy, deep brain stimulation)
– Tissue transplant

31. ….diseases of basal ganglia
• Essential tremor (ET)
– Most common neurological cause of postural or
action tremor (up to 5% of population)
• Peak age 2nd and 6th decades
• M=F
• Familial tremor (AD) or sporadic (benign ET)
– Neuropathological basis:
• Brainstem and cerebellar lesions??
• Increased risk for PD and dementia ?

32. ….diseases of basal ganglia
• ET diagnostic criteria:
– Bilateral action tremor of hands & forearms (4-10Hz)
• Chronic disorder (>3yrs)
• Beneficial response to alcohol
– No neurological signs except cogwheel rigidity
– Positive family history (>50%)
• Treatment:
– Medical (propranolol & primidone) and surgical
(DBS & thalamotomy)

33. ….diseases of basal ganglia
• Sydenham chorea (SC)
– One of the major clinical criteria of ARF (in 18-36%)
• 1-8months after group A streptococcal pharyngitis (often
purely)
– Commonest acquired chorea in childhood, F:M 2:1
• Insidious onset of chorea, emotional lability & hypotonia
• Elevated anti-DNAse B & ASO antibodies
• Exclusion of other causes of chorea
• ARF= acute rheumatic fever

34. ….diseases of basal ganglia
• Reversible abnormalities of the striatum
– Improves gradually, mean duration of 12 to 15 wks
(occasionally ≥2yrs)
– Recurence rate 20-30%
• SC treatment:
– Valproate, phenobarbital, haloperidol & diazepam
(± prednisone)
– Benzathin penicillin prophylaxis

35. • Tardive dyskinesia (TD)
– Diagnosis of TD
• Occurrence of involuntary movements
– Variable mixture of orofacial dyskinesia (athetosis, chorea, tics
and facial grimacing ) and dystonia
• History of ≥1 month of dopamine receptor blocking
agents (antipsychotic drugs and metoclopramide) use
• Exclusion of other causes of abnormal movements
– Dopamine receptor supersensitivity ± structural
cellular alterations in the brain

36. • TD treatment:
– DC or change offending drug
• Often reversible (50-90%) within several months
– Pharmacologic treatments
• Benzodiazepines, botulinum toxin or anticholinergics
– Resume antipsychotic drugs
• Suppress TD (in treatment-resistant)
– DBS (in unresponsive)

37. Summary
• Extrapyramidal disorders don't cause weakness
• Diagnosis of movement disorders is essentially
clinical
• Underlying cause of movement disorders can
be identified with focused work-up
• Treatment of movement disorders requires
working knowledge of basal ganglia
neurobiochemisty