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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 ?