the motor regulator - med study...
TRANSCRIPT
![Page 1: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/1.jpg)
1) Basal ganglia/nucleus
The motor regulator
![Page 2: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/2.jpg)
Neural structures involved in the control of movement
![Page 3: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/3.jpg)
- Components of the basal ganglia
- Function of the basal ganglia
- Connection and circuits
- Functional circuitry of the basal ganglia
e.g., direct and indirect pathways, transmitters
- Symptoms and disorders discussed
Basal Ganglia
![Page 4: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/4.jpg)
Parts
![Page 5: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/5.jpg)
Atlas Fig. 6-37
![Page 6: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/6.jpg)
Atlas Fig. 6-36
![Page 7: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/7.jpg)
Atlas Fig. 6-35
![Page 8: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/8.jpg)
Atlas Fig. 6-34
![Page 9: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/9.jpg)
![Page 10: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/10.jpg)
Atlas Fig. 6-32
![Page 11: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/11.jpg)
Atlas Fig. 6-32
![Page 12: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/12.jpg)
Function of the basal ganglia
![Page 13: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/13.jpg)
Direct = Dark grey – Red – Blue – Light grey
Indirect = Dark grey – Green – Blue – Light grey
Text Fig. 26-9
![Page 14: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/14.jpg)
Medium spiny neuron projections
![Page 15: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/15.jpg)
Neurons of the basal ganglia
![Page 16: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/16.jpg)
Connections and circuits
![Page 17: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/17.jpg)
Connections and circuits
![Page 18: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/18.jpg)
Motor Loop
![Page 19: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/19.jpg)
Visuomotor Loop
![Page 20: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/20.jpg)
Executive Loop
Dorsomedial
![Page 21: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/21.jpg)
Motivational Loop
![Page 22: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/22.jpg)
Functional loops
![Page 23: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/23.jpg)
Text Fig. 26-10A,B
![Page 24: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/24.jpg)
_
+
+
Text Fig. 26-10A,B
![Page 25: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/25.jpg)
Text Fig. 26-10C,D
![Page 26: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/26.jpg)
+ _
+
+ Text Fig. 26-10C,D
+
![Page 27: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/27.jpg)
Modulators (associated nuclei)
![Page 28: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/28.jpg)
- Subthalamic Nucleus ?????
- Nigral Complex
- Parabrachial Pontine Reticular Formation
- Zona inserta
- Ventral Basal Nuclei
Modulators (associated nuclei)
![Page 29: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/29.jpg)
Modulators (associated nuclei)
- Subthalamic Nucleus ?????
- Nigral Complex
- Parabrachial Pontine Reticular Formation
- Zona inserta
- Ventral Basal Nuclei
![Page 30: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/30.jpg)
Nigral modulation
R
glu
DA
Direct transmission
EPSP
![Page 31: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/31.jpg)
glu
DA
Almost No direct effect of DA
Direct transmission vs. modulation
![Page 32: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/32.jpg)
R
enhanced or diminished
response
Modulation
glu
DA D1-Rs in the direct pathway: 1) increase GluR phosphorylation
2) alters ionic conductances
to amplify cortical input
Direct transmission vs. modulation
Striatal medium spiny neuron
![Page 33: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/33.jpg)
R
enhanced
or diminished response
Modulation
glu
DA
Direct transmission vs. modulation
D2-Rs in the indirect pathway: 1) increase GluR phosphorylation
2) alters ionic conductances
to dampen cortical input
Striatal medium spiny neuron
![Page 34: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/34.jpg)
Direct and Indirect Pathways
(Including the Substantia Nigra
Text Fig. 26-14A,B
![Page 35: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/35.jpg)
Hypokinetic disorders
• insufficient direct pathway output
• excess indirect pathway output
Motor behavior is determined by the balance
between direct/indirect striatal outputs
![Page 36: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/36.jpg)
Corticostriatial
Striatopallidal
Pallidothalammic
Thalamocortical
Corticospinal, Corticonuclear
Text Fig. 26-12A,B
![Page 37: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/37.jpg)
Text Fig. 26-10A,B
![Page 38: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/38.jpg)
Hypokinetic disorders
• insufficient direct pathway output
• excess indirect pathway output
Hyperkinetic disorders
• excess direct pathway output
• insufficient indirect pathway output
Motor behavior is determined by the balance
between direct/indirect striatal outputs
![Page 39: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/39.jpg)
Corticostriatal, Corticosubthalamic
Striatopallidal
Pallidosubthalamic
Subthalamopallidal
Pallidothalamic
Thalamocortical
Corticospinal, Corticonuclear
Text Fig. 26-12C,D
![Page 40: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/40.jpg)
Involuntary (unwanted) movements
• Chorea (dance-like)
• Ballismus
• Dystonia (torsion spasm)
• Athetosis (changeable or writhing
movements)
• Choreoathetosis
• athetotic dystonia
Hyperkinetic symptoms
(Choreatic symptoms)
![Page 41: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/41.jpg)
Basal Ganglia disorders
![Page 42: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/42.jpg)
Parkinson’s disease
Pathophysiology
Primary: loss of
nigrostriatal DA
projection
SNc
Striatum
Michael J. Fox Muhammad Ali
![Page 43: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/43.jpg)
Normal Parkinson’s
disease
Human midbrain
![Page 44: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/44.jpg)
Loss of Dopaminergic Nigral Connections
Text Fig. 26-14C,D
![Page 45: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/45.jpg)
Parkinson’s disease
![Page 46: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/46.jpg)
Motoric
Tremor (~4-5 Hz, resting)
Bradykinesia
Rigidity
Loss of postural reflexes
Depression
Dementia
Parkinson’s disease
Symptoms
![Page 47: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/47.jpg)
Parkinson’s disease Treatment
L-DOPA
This is initially effective, but after 5-10
years, 50% of patients develop DOPA-
induced dyskinesia.
![Page 48: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/48.jpg)
Parkinson’s disease Treatment
L-DOPA
This is initially effective, but after 5-10
years, 50% of patients develop DOPA-
induced dyskinesia.
Deep brain stimulation
The indirect pathway is increased in
Parkinson’s. This parkinsonian patient
has bilateral STN stimulating
electrodes:
high frequency stimulation inactivates
the STN.
![Page 49: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/49.jpg)
Parkinson’s disease Treatment
L-DOPA
This is initially effective, but after 5-10 years,
50% of patients develop DOPA-induced
dyskinesia.
Deep brain stimulation
SN or subthalamic nucleus (STN)/ globus pallidus
interna (GPi)
high frequency stimulation inactivates the STN or
GPi.
![Page 50: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/50.jpg)
Parkinson’s disease Treatment
L-DOPA
Deep brain stimulation
Novel treatments
Anti cholinergic , anti AMPA, & A2
![Page 51: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/51.jpg)
Hyperkinetic disorders:
choreatic syndromes
1. Huntington’s chorea
2. Dystonia
3. Tardive dyskinesia
4. DOPA-induced dyskinesia
5. Hemiballismus
6. Tourette’s syndrome
Causes:
Genetic (autosomal dominant)
Genetic or idiopathic Chronic neuroleptic use Parkinson’s therapy
Unilateral vascular accident, typically subthalamic nucleus
Excessive D2-subtype DA receptor expression(?)
![Page 52: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/52.jpg)
Choreatic symptoms
Involuntary (unwanted) movements
• Chorea (dance-like)
• Athetosis (changeable or writhing movements)
• Dystonia (torsion spasm)
![Page 53: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/53.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
![Page 54: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/54.jpg)
Huntington’s disease
Pathophysiology
• Atrophy of striatum
• Loss of striatal GABAergic neurons
• Neuropathological sequence
• start , rostral and medial then caudal and
lateral
absentmindedness, irritability, depression,
clumsiness, and sudden
falls. Choreiform
![Page 55: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/55.jpg)
Huntington’s disease pathology
Huntington’s
Normal
![Page 56: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/56.jpg)
Huntington’s disease
![Page 57: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/57.jpg)
Huntington’s disease
Symptoms
Early motor signs
chorea (brief,
involuntary
movements)
dystonia (abnormal
postures)
Choreatic gait
Dystonic movements
![Page 58: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/58.jpg)
Huntington’s disease
Cognitive abnormalities Executive function (complex tasks)
Recent and remote memory (poor retrieval)
Psychiatric changes Depression
Psychosis
Later decline Immobility
Weight loss
Death within 10-25 years (often from pneumonia)
![Page 59: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/59.jpg)
Etiology of Huntington’s disease
Huntingtin mutation
• Mutation near 5’ end contains >>CAG repeats
• Produces protein with excess glutamines near NH2 terminus
Why cell death?
• Not yet certain
• Excitotoxicity? Glutamate acting via NMDA receptors can kill medium spiny neurons; glutamate antagonists block
![Page 60: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/60.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
Cervical dystonia (torticollis)
After botulinum toxin
![Page 61: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/61.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
Axial (thoracic and/or
lumbar) dystonia
![Page 62: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/62.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
![Page 63: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/63.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
*DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
*50% of PD patients on L-DOPA will develop DOPA dyskinesia
![Page 64: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/64.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus
Tourette’s syndrome
![Page 65: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/65.jpg)
Hyperkinetic disorders: choreatic syndromes
Huntington’s disease
Dystonia
Tardive dyskinesia
DOPA-induced dyskinesia
Hemiballismus – unilateral
STN stroke
Tourette’s syndrome
After treatment with the D2-R blocker sulpiride
![Page 66: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/66.jpg)
Atlas Fig. 8-33A,B
![Page 67: The motor regulator - Med Study Groupmsg2018.weebly.com/uploads/1/6/1/0/16101502/basal-ganglia-physiology_11.pdf · The motor regulator . Neural structures involved in the control](https://reader031.vdocument.in/reader031/viewer/2022041503/5e22cc61739060766f05e61c/html5/thumbnails/67.jpg)
Sydenham Chorea