82608742 Basal Ganglia
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The basal ganglia
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Basal Ganglia
Consist of Four Nuclei
striatum
caudate and putamen globus pallidus
substantia nigra
subthalamus
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The basal ganglia are the principal
subcortical components of a family of
parallel circuits linking the thalamus
with the cerebral cortex
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Motor Function of the Basal Ganglia
control of complex patterns of motor activity
using scissors
throwing balls
shoveling dirt
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Function of the Basal Ganglia?
not much is known about the specific functions of
each of these structures
thought to function in timing and scaling of
motion and in the initiation of motion
most information comes from the result of
damage to these structures and the resulting
clinical abnormality
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Caudate extends into all
lobes of the cortex andreceives a large input from
association areas of the
cortex
Mostly projects to globus
pallidus, no fibers to sub-thalamus or substantia
nigra
Most motor actions occur
as a result of a sequence ofthoughts. Caudate circuit
may play a role in the
cognitive control of motor
functions
Caudate Circuit
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Putamen Circuit
Mostly from premotor andsupplemental motor cortex toputamen then back to motor
cortex.
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Neurotransmitters in the Basal Ganglia
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Lesions of Basal Ganglia
globus pallidus
athetosis - spontaneous writing movements of thehand, arm, neck, and face
putamen chorea - flicking movements of the hands, face, and
shoulders
substantia nigra
Parkinson's disease - rigidity, tremor and akinesia
loss of dopaminergic input from substantia nigra tothe caudate and putamen
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subthalamus
hemiballismus - sudden flailing movements of
the entire limb
caudate nucleus and putamen
huntingtons chorea - loss of GABA containing
neurons to globus pallidus and substantia nigra
Lesions of Basal Ganglia
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Integration of Motor Control
spinal cord level
preprogramming of patterns of movement of allmuscles (i.e., withdrawal reflex, walkingmovements, etc.).
brainstem level maintains equilibrium by adjusting axial tone
cortical level
issues commands to set into motion the patterns
available in the spinal cord controls the intensity and modifies the timing
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Integration of Motor Control (contd)
cerebellum
function with all levels of control to adjust cordmotor activity, equilibrium, and planning ofmotor activity
basal ganglia
functions to assist cortex in executing
subconscious but learned patterns of movement,and to plan sequential patterns to accomplish apurposeful task
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Overall scheme for
integration of
motor function
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History of Parkinsons disease (PD)
First described in 1817 by an English physician,
James Parkinson, in An Essay on the Shaking
Palsy.
The famous French neurologist, Charcot, further
described the syndrome in the late 1800s.
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Epidemiology of PD
The most common movement disorder
affecting 1-2 % of the general population
over the age of 65 years.
The second most common
neurodegenerative disorder afterAlzheimers disease (AD).
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Incidence of PD
Age
Inc
idence/
1000
00
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Prevalence of PD
Age
Prevalence/
1
000
00
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Epidemiology of PD
May be less prevalent in China and other Asian
countries, and in African-Americans.
Prevalence rates in men are slightly higher than in
women; reason unknown, though a role for
estrogen has been debated.
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Risk factors of PD
Age -the most important risk factor
Positive family history
Male gender
Environmental exposure: Herbicide and pesticide exposure,
metals (manganese, iron), well water, farming, rural residence,wood pulp mills; and steel alloy industries
Race
Life experiences (trauma, emotional stress, personality traits
such as shyness and depressiveness)? An inverse correlation between cigarette smoking and caffeine
intake in case-control studies.
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Clinical features of PD
Three cardinal
features:
resting tremor bradykinesia
(generalized
slowness of
movements) muscle rigidity
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Clinical features of PD
Resting tremor: Most common first symptom, usually asymmetric
and most evident in one hand with the arm at rest.
Bradykinesia: Difficulty with daily activities such as writing,shaving, using a knife and fork, and opening buttons; decreased
blinking, masked facies, slowed chewing and swallowing.
Rigidity: Muscle tone increased in both flexor and extensor
muscles providing a constant resistance to passive movements of
the joints; stooped posture, anteroflexed head, and flexed knees
and elbows.
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Additional clinical features of PD
Postural instability: Due to loss of postural reflexes.
Dysfunction of the autonomic nervous system: Impaired
gastrointestinal motility, bladder dysfunction, sialorrhea,
excessive head and neck sweating, and orthostatic hypotension.
Depression: Mild to moderate depression in 50 % of patients.
Cognitive impairment: Mild cognitive decline including impaired
visual-spatial perception and attention, slowness in execution of
motor tasks, and impaired concentration in most patients; at least
1/3 become demented during the course of the disease.
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Neuropathology of PD
Eosinophilic, round intracytoplasmic inclusions
called lewy bodies and Lewy neurites.
First described in 1912 by a German
neuropathologist - Friedrich Lewy.
Inclusions particularly numerous in the substantianigra pars compacta.
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Lewy bodies
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Neuropathology of PD: Lewy bodies
Not limited to substantia nigra only; also found in the locus
coeruleus, motor nucleus of the vagus nerve, the
hypothalamus, the nucleus basalis of Meynert, the cerebralcortex, the olfactory bulb and the autonomic nervous system.
Confined largely to neurons; glial cells only rarely affected.
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Functional neuroanatomy of PD
Substantia nigra: The major origin of the dopaminergic
innervation of the striatum.
Part of extrapyramidal system which processes information
coming from the cortex to the striatum, returning it back to
the cortex through the thalamus.
One major function of the striatum is the regulation of
posture and muscle tonus.
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Neurochemistry of PD
Late 1950s: Dopamine (DA) present in mammalian brain,
and the levels highest within the striatum.
1960, Ehringer and Hornykiewicz: The levels of DA
severely reduced in the striatum of PD patients.
PD symptoms become manifest when about 50-60 % of
the DA-containing neurons in the substantia nigra and
70-80 % of striatal DA are lost.
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Dopamine synthesis
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Dopamine pathways in human brain
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Therapy of PD: levodopa
Late 1950s: L-dihydroxyphenylalanine (L-DOPA; levodopa),
a precursor of DA that crosses the blood-brain barrier,
could restore brain DA levels and motor functions in
animals treated with catecholamine depleting drug
(reserpine).
First treatment attempts in PD patients with levodopa
resulted in dramatic but short-term improvements; took
years before it become an established and succesfull
treatment.
Still today, levodopa cornerstone of PD treatment; virtually
all the patients benefit.
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Therapy of PD: limitations of levodopa
Efficacy tends to decrease as the disease progresses.
Chronic treatment associated with adverse events(motor fluctuations, dyskinesias and
neuropsychiatric problems).
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Therapy of PD: limitations of levodopa
Does not prevent the continuous degeneration
of nerve cells in the subtantia nigra, the
treatment being therefore symptomatic.
Inhibition of peripheral COMT b entacapone
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Inhibition of peripheral COMT by entacapone
increases the amount of L-DOPA and dopamine
in the brain and improves the alleviation of PD
symptoms.
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Therapy of PD: Other treatments
DA receptor agonists (bromocriptine,
pergolide, pramipexole, ropinirole,
cabergoline)
Amantadine
Anticholinergics
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Diagnosis of PD
History and clinical examination
Positron Emission Tomography (PET) or Single-photon
Emission Computed Tomography (SPECT) withdopaminergic radioligands
Exclusion of several causes of secondary Parkinsonism
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Summary
1-2 % of the general population over the age of 65 y
Lewy bodies and Lewy neurites particularly in the substantia
nigra pars compacta dopaminergic neurons projecting to
striatum
DA levels severely reduced in striatum.
Resting tremor, bradykinesia, muscle rigidity
Levodopa and other dopaminergic drugs
No treatment which would prevent the continuous
degeneration of nerve cells in the substantia nigra and resultingstriatal DA loss
MCQ
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Which circuit in the basal ganglia is thought to be involved in the cognitive control of motor functions?
A.Caudate circuit
B.Putamen circuit
C.Papez circuit
D.Nigropallidothalamic circuit
ANS: A
Chorea and choreiform movement is a sign of dysfunction in which brain region?
A.Substantia nigra
B.Caudate nucleus and putamen
C.Subthalamic nucleus
D.Thalamus
ANS: B
Parkinson's disease is the result of
A.Disruption of the putamen circuit
B.Loss of GABA input from caudate nucleus and putamen to the substantia nigra
C.Loss of dopaminergic input from substantia nigra to the caudate nucleus and the putamen
D.Loss of serotonin input from substantia nigra to the thalamus and subthalamus
ANS: C
MCQs
MCQ
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MCQs
Neurological disease associated with the globus pallidus produces which type of symptom?
A.Rigidity
B.Chorea
C.Hemiballismus
D.Athetosis
ANS: D
Which of the following structures is notconsidered to be part of the basal ganglia?
A.Caudate nucleusB.Red nucleus
C.Substantia nigra
D.Putamen
ANS: B
Hemiballismus is associated with damage or dysfunction of which of the following structures?A.Thalamus
B.Caudate nucleus
C.Subthalamus
D.Red nucleus
ANS: C
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Parkinsonism and
Parkinsons disease
Problem based learning
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Task
Read the case detailsIdentify thekeywords
Define importantterms
Use our knowledgeof basic sciences to
interpret the variousabnormalities
Management of the
case
Home work
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Case Details
A 58-year-old male patient who was a univeristyprofessor by occupation, was seen by the neurologist
He visited the neurologist because for the past 3months, he was experiencing a recent onset of an
intermittent shaking movement involving both hisupper limbs that occurs primarily at rest.
He also had difficulty in getting out of bed in themornings
But once he got up he carried on with his daily work He also complained of difficulty in turning his body
rapidly when someone called him from the back
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Key words
A 58-year-old male patient who was a univeristyprofessor by occupation, was seen by the neurologist
He visited the neurologist because for the past 3months, he was experiencing a recent onset of an
intermittent shaking movement involving both hisupper limbs that occurs primarily at rest.
He also had difficulty in getting out of bed in themornings
But once he got up he carried on with his daily work He also complained ofdifficulty in turning his body
rapidly when someone called him from the back
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Questions
What are the presenting symptoms in this
patient ?
Why do you think he went to a neurologist ?
Which parts of the CNS are involved in thecontrol of movement ?
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Case details
Neurologic evaluation reveals mild upper limb
rigidity in addition to the resting tremor in the
upper limbs.
The doctor noticed that all the movement of thepatient were slow.
On further neurological examination, when the
patient is asked to walk to and fro his arms do notsway and he finds it difficult to turn around.
His blood pressure and vital signs are normal
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Key words
Neurologic evaluation reveals mild upper limb
rigidity in addition to the resting tremor in the
upper limbs.
The doctor noticed that all the movement of thepatient were slow.
On further neurological examination, when the
patient is asked to walk to and fro his arms do notsway and he finds it difficult to turn around.
His blood pressure and vital signs are normal
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Questions
What is rigidity ? (Increased tone of the
muscles due to a lesion of the extra pyramidal
system)
What do you mean by tremor ?
What is the neurological term for slowness of
movement ?
What does the triad of tremor rigidity and
bradykinesia suggest ?
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Case details
After a detailed history and examination, the
neurologist concludes that the patient has
features ofParkinsonism.
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Keywords
After a detailed history and examination, the
neurologist concludes that the patient has
features ofParkinsonism.
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Questions
What is Parkinsonism ?
Parkinsonism is a neurological syndrome
characterized by tremor, hypokinesia, rigidity,
and postural instability
Which part of the nervous system is involved
with parkinsonism ?
How does the body perform a smooth,
controlled and coordinated movement?
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Key aspects of a goal directed movement
An individual must first be aware of thesurrounding environment and his position inspace. This information is generated throughsomatosensory, proprioceptive, and visualsensory inputs to the posterior parietal cortex.
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The individual then decides what action is desired.
This is accomplished via the parietal and anterior
frontal lobes, which are extensively interconnected.
These regions are thought to be important forabstract thought and decision making, and hence it is
here that decisions about what actions to take are
made and their likely outcomes are judged.
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A plan must then be constructed to determine howthe actions will be carried out. This is performed in
the premotor cortex (PMC) and supplemantary
motor areas (SMA), where axons from the both the
prefrontal and and parietal cortex converge. In this
area the signals indicating what actions are desired
are converted into signals that indicate how the
actions will be perfomed.
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Finally, a command to begin the action must beissued and the plan must be implemented. Thisinvloves the primary motor cortex, which,together with the PMC and SMA, contributesmost of the axons to the descending corticospinaltract. From this region of the brain signals passout to the muscles, converting the plan of actioninto an actual movement.
Wh t th t t i th b i
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Cerebellum Basal ganglia
What are the structures in the brainthat regulate and coordinate motor
activity ?
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Cerebellum
The main function of the cerebellum is the coordination of motoractivities.
Commands to initiate movement come from the somatomotorcerebral cortex, but the cerebellum fine-tunes motor control, givingsmoothness of motion and exactness of positioning.
The cerebellum makes comparisons of internal and external
feedback signals to correct ongoing movements. Lesions of the cerebellum result in movements that are jerky and
that overshoot or undershoot their intended mark.
The cerebellum is the site to ensure well-timed and co-ordinatedmovements and sequences.
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The term basal ganglia relate to a set of nucleithat are located deep in the hemispheres.
The basal ganglia are involved in theregulation of cortically initiated motor activity,which if disturbed leads to some form ofmovement disorder
Basal Ganglia
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the basal ganglia receive inputs from the cerebral cortex , the
inputs go onward to the various parts of the basal ganglia and
then signals go back to the cerebral cortex via the thalamus. What could be the purpose of this loop?
Evidently the basal ganglia function to maintain the muscle
tone needed to stabilize joint position (as, for example,holding a glass of water while talking) or to inhibit muscle
tone during the initiation of movement.
Interruption of the feedback loops of the basal ganglia bydamage to one of its structures results in the uncontrollable
oscillations manifested as tremors or as other movement
disorders.
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Home work
What are the parts of the basal ganglia ?
What are the functions of basal ganglia ?
What are the types of movement disorders ?
What are the causes of Parkinsonism ?
List the various clinical signs of parkinsonism.
What is Levo Dopa ?