Download Chapter 16: Basal Ganglia

Chapter 16:
Basal Ganglia
Outline
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Anatomy
Circuitry
Clinical concepts
Clinical cases
Overview of function
• BG Influence descending motor systems by
participating in complex networks
• Do not directly project to periphery
• Lesions lead to two broad phenotypes
– Hypokinetic
– Hyperkinetic
Anatomy
• Grey matter nuclei deep within white matter
BASAL GANGLIA
Striatum
Cellular bridges
Caudate
(head, body, tail)
Putamen
Globus pallidus
Subthalamic nucleus
Substantia nigra
Pars reticulata, pars compacta
Lentiform nucleus
Anatomy
• Relationships
– Head of caudate + lentiform nucleus separated by
Anterior limb of internal capsule
– Lentiform nucleus and thalamus separated by
Posterior limb internal capsule
– So:
• Caudate and thalamus always medial to IC
• Putamen and GP always lateral to IC
Brief review vascular supply
• Main supply via lenticulostriate branches of
MCA
• Recurrent artery of Heubner (ACA)
– Head of caudate and anterior lentiform nucleus
• Anterior choroidal artery (ICA)
– Medial GP
Input, Output, Connections
Inputs
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Main input to BG is to striatum
Cortex  +, Glutamate
SNpc  + and -, DA
Thalamus  +, Glutamate
– Intralaminar nuclei in internal medullary lamina
• Raphe nuclei  modulation, serotonin
Outputs
• SNpr and GPi are main outputs, inhibitory
•  Thalamus
– VL, VA, intralaminar, mediodorsal
•  Pontomedullary reticular formation
– Affects reticulospinal tract
•  Superior colliculus
– Affects tectospinal pathways
Intrinsic connections
• Excitatory/inhibitory connections within BG
• Two main pathways:
– Direct pathway
– Indirect pathway
– Both pathways exert effect via thalamus
– Both receive input from SNpc (DAergic
nigrostriatal pathway)
Direct and Indirect Pathways
Parallel BG pathways
• Motor channel
– Regulation of movement
• Oculomotor channel
– Regulation of eye movements
• Prefrontal channel
– Cognitive processes involving frontal lobes
• Limbic channel
– Limbic regulation of emotions and motivational drives
– Role in neurobehavioral and psychiatric disorders
Understanding movement disorders
based on Pathways
• Parkinson’s disease
– Degeneration of DA-ergic neurons in SNpc
• Hemiballismus
– Contralateral STN lesion
• Huntington’s disease
– Degeneration of striatum, initially indirect pthway
Understanding movement disorders
Key Clinical Concept 1 –
Movement Disorders
• “Movement disorders” usually refers to
abnormal movement 2ary to BG lesion
• Exert effect via projections to cortex
• Gradient of hypo- to hyperkinetic
Bradykinesia, Hypokinesia, Akinesia
• BG lesions that increase inhibition of thalamus
– Loss of DA-ergic input from SNpc
• Typified by PD
– Loss of inhibition of SNr/GPi via direct pthwy
– Loss of inhibition of STN
• Other lesions
– Diffuse lesions of frontal cortex, subcortical white
matter, thalami, reticular formation
– Depression, schizophrenia
Rigidity
• Increased resistance to passive limb mvment
• Spasticity
– Velocity-dependent rigidity in UMN lesions
• Clasp-knife spasticity (corticospinal tract lesion)
– Increase then decreased in resistive tone as stretch
• Lead-pipe rigidity (BG lesion)
– Continuous resistive tone throughout stretch
• Cogwheel rigidity (PD and related disorders)
– Rigidity with superimposed tremor
• Paratonia or gegenhalten (frontal lobe dysfctn)
– Active resistance to limb movement
Dystonia
• Abnormal, distorted position of limbs, trunk, face
– May be focal, unilateral or generalised
• Usually, no focal lesion in BG is found
• Examples
– Torticollis, blepharospasm, spasmodic dysphonia,
writer’s cramp
• Etiology
– Antipsychotic or anti-emetic medications
• Acute or after long-term use (tardive dyskinesia)
– BG lesions 2ary infarct, tumor, abscess
– Wilson’s, Huntington’s, Parkinson’s disease
Athetosis
• Writhing, twisting movements of limbs, face,
trunk
• May merge with chorea  choreoathetosis
• Etiology
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Perinatal hypoxia involving BG, Kernicterus
Wilson’s disease
Ataxia telangiectasia
Huntington’s disease
Antipsychotic and anti-emetic medications
Treatment of PD with levodopa
Chorea
• Nearly continuous, involuntary movements that have fluid
or jerky, varying quality
• Involves limbs, trunk, neck, face, resp muscles
• Range from mild low-amplitude to severe, large-amplitude
movements
• Worsen with distraction and ambulation
• Etiology
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Huntington’s disease
Benign familial chorea
Sydenham’s chorea
Lupus
Antipsychotics, anti-emetics, levodopa in PD, phenytoin
Ballismus
• Movements of proximal limb muscles with
large amplitude, more rotatory or flinging
than chorea
• Hemiballismus
– Unilateral movements 2ary to contralateral BG
lesion
– Classically, lacunar infarct in STN
– Other causes: hemorrhage, tumor, infection
Tics
• Sudden, brief action
– Preceded by urge to perform action
– Followed by sense of relief
• Motor tics – usu. involve face, neck
• Vocal tics – variable, can be elaborate
• Etiology
– Tourette’s syndrome
– Idiopathic tic disorders
– 2ary to encephalitis, infarcts, hemorrhage, tumors
Myoclonus
• Sudden, rapid muscular jerk that is focal,
unilateral or bilateral
• Localisation: cortex, cerebellum, BG, brainstem,
spinal cord
• Etiology
– Anoxic brain injury, encephalitis, toxic and metabolic
encephalopathies
– Epileptic cortical activity (e.g. JME)
– Paraneoplastic disroders (SCLC, ovarian, breast)
– CJD, CBD, late in Alzheimer’s
Tremor
• Rhythmic or semi-rhythmic oscillating mvmnts
• Both agonist and antagonist muscles involved
• Classification
– Resting
• Parkinsonian (3-5Hz), cerebellar (rubral), palatal
– Postural
• When pt’s limbs actively held in a position
• Essential tremor (5-8Hz), toxic/metabolic, physiologic, NM
disorder, PD, cerebellar
– Intention (ataxic)
• Appears when trying to move limb towards target
• Cerebellar appendicular ataxia, postural tremor
Key Clinical Concept 2 –
Idiopathic Parkinson’s Disease
• Sporadic, unknown etiology, onset 40-70 y.o.
– Rarely, familial
• Loss of DA-ergic neurons in SNpc
– Lewy bodies in remaining DA-ergic neurons
– Loss of pigmented neurons elsewhere in CNS
• Diagnosis based on clinical features
Idiopathic PD – Clinical Features
• Resting tremor
• Parkinsonian gait
– Slow, shuffling, en bloc
• Bradykinesia/hypokinesia
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Masked facies
Hypophonia
Slow saccades
Micrographia
• Cogwheel rigidity
• Postural instability
• Retropulsion
turn, decreased arm
swing
• Dementia
– 15-40%, late
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Bradyphrenia
Starts unilaterally
Insidious progression
Responds to levodopa
L-dopa in Idiopathic PD
• Most effective drug for treatment
• If no response to treatment  consider
alternative diagnosis
• As disease progresses, on-off phenomena
– Abnormal regulation of DA levels
– May manage with SR, COMT inhibitors, MAOIs
• Other treatment options
– DA agonists (e.g. pramipexole)
– Anticholinergics (e.g. benztropine)
– MAOI (e.g. selegiline)
Parkinsonism Plus Syndromes
• Neurodegenerative conditions w/ atypical
parkinsonism
– Symmetrical Sx, no resting tremor, early postural
instability, little response to DA-ergic agents
• Examples
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Multisystem atrophy
Progressive supranuclear palsy
Lewy body dementia
Cortical basal ganglionic degeneration
Huntington’s, Wilson’s
Huntington’s Disease
• Autosomal dominant inheritance pattern
– Gene on chromosome 4, CAG trinuc repeats
• 4-5/100,000, usu age of onset 30-50 y.o.
• Progressive atrophy of striatum
– Caudate > putamen > Nacc
– All 4 functions of BG affected
• Cortical atrophy later in course
• Diagnosis
– Clinical features, family Hx, genetic testing
Clinical Features
• Motor control
– Clumsiness, subtle chorea, athetosis, tics, dystonic
posturing
• Eye movement control
– Slow saccades, impaired smooth pursuit, difficulty
initiating saccades
• Cognition
– Decreased attn, decreased memory, impaired
executive function
• Emotion regulation
– Depression, anxiety, OCD, manic-like behavior
Case 1
• 65M, HIV positive
• HPI
– Involuntary flinging mvmnts of Rt arm/leg
– Worsened over 1 mo
– Difficult to walk and use hand
• O/E
– Continuous wild, uncontrollable flapping and circular
movements of Rt arm
– Jerky mvments of Rt leg
– Unsteady gait, falling to right
Case 1
• What would you call this movement disorder?
• On the basis of the symptoms and signs,
where is the lesion?
• What is the most likely diagnosis and what are
some possibilities?
Case 1
• Decreased inhibition of
contralateral thalamus
– Subthalamic lesion
– Damage to indirect
pathway
Case 1
Case 2
• 35M, recent-onset jerky mvmnts, marital
problems
• HPI
– Occasional irregular jerking of head, trunk, limbs over
past months
– Occasional stumbling with fall down stairs
– Bitter arguments with wife
– Pt denied involuntary mvmnts, gait change, mood
disturbance
• Family History
Case 2
• Mental status:
– Normal orientation,
speech, memory.
– Blunted affect
• CN:
– Slow saccades
• Motor:
– Rare, brief, irregular
mvments face, neck,
trunk
– Slightly decreased tone
• Reflexes
– Normal and symm
• Coordination
– Normal
• Gait
– Unsteady tandem
Case 2
• On the basis of SSx, which of the four channels
through BG are involved?
• Which part of BG could lead to this disorder?
• What is most likely diagnosis?
• What genetic abnormality causes this
disorder?
• What parts of the brain are predominantly
affected?
Case 3
• 53M, Rt-handed, 2nd opinion for bradykinesia,
tremor, rigidity, unsteady gait
• HPI
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10 yrs ago, slowness and difficulty using Rt arm
8 yrs ago shaking of Rt arm and leg
Dx PD  Sinemet started, beneficial
Progressively worse Sx
• Tremor of whole body, slower, stiffer, difficulty initiating
movements.
– Family Hx negative, no antipsychotic meds
Case 3
• Mental status
– Micrographia
• CN
– Mask-like facies,
hypophonia
• Motor
– 4Hz tremor U+L/E, Rt > Lt
– Cogwheel rigidity
– FFM, RAM slow
• Reflexes
– No extinction of glabellar
(+ve Myerson)
• Coordinationn
– Slow, no ataxia
• Gait
– Can’t raise from chair w/o
assistance
– Slow, stiff gait, stooped
posture, short steps,
decreased arm swing
– En bloc turning
Case 3
• Idiopathic or atypical parkinsonism?
• Degeneration of neurons in which structure
1arily responsible for idiopathic PD?
• What is main neurotransmitter?
• How does loss of neurons lead to hypokinetic
disorder?
• If pt has on-off phenomena, what procedures
can be recommended?
Case 4
• 48 F
• HPI
– Difficulty type-writing 2ary bilat finger stiffness
– Unsteady gait, multiple falls
– No benefit with levodopa
• Exam 5 yrs after symptom onset
– Slow saccades, masked facies, slow dysarthric speech
– Prominent bilateral bradykinesia and rigidity of axial
and neck muscles
– Slow, shuffling gait with retropulsion
– No ataxia or autonomic dysfunction
Case 4
• Idiopathic vs atypical parkinsonism?
• What is most likely diagnosis?
• Which neurons degenerate in this condition?
Case 4
• Striatonigral
degeneration
– Loss of DA-ergic neurons
in SNpc AND
– Degeneration of striatal
neurons projecting to
GPi and SNpr
• Therefore, decreased
transmission of DA-ergic
stimulation from striatum
to GPi/SNpr
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the posterior parietal cortex clearly plays a role in voluntary movements, by
assessing the context in which they are being made. The parietal cortex receives
somatosensory, proprioreceptive, and visual inputs, then uses them to determine
such things as the positions of the body and the target in space. It thereby
produces internal models of the movement to be made, prior to the involvement
of the premotor and motor cortices.
Within the posterior parietal cortex, two particular areas are distinguished. Area 5
receives information from somatosensory areas 1, 2, and 3 of the cortex. Area 7
further integrates the already highly integrated signals from the visual areas of the
cortex, such as MT and V5.
The parietal lobes are themselves closely interconnected with the prefrontal areas,
and together these two regions represent the highest level of integration in the
motor control hierarchy. It is here that the decisions are made about what action
to take. The posterior parietal and prefrontal areas send their axons to Area 6
which, once it has been informed about the kind of action to take, helps to
determine the characteristics of the appropriate movement for this purpose.
Direct pathway
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From striatum directly to SNpr, GPi
Cortex stimulates striatum 
Striatum inhibits SNpr, GPi 
Loss of inhibition of thalamus 
Facilitation of movement via increased
thalamic output to motor and premotor
cortex
Indirect pathway
Indirect pathway
• Net effect
– Increased inhibition of thalamus
– Therefore inhibition of movements
Some Nomenclature
• GPi  thalamus output pathway
– Ansa lenticularis
• Fibers loop ventrally under IC
– Lenticular fasciculus
• Fibers penetrate straight through IC
– Join to form thalamic fasciculus
• GPe  Subthalamic nucleus and  GPi
– Subthalamic fasciculus
Understanding Movement Disorders
• Hemiballismus
– Wild flinging movement of extremities
– Classically, contralateral subthalamic nucleus lesion
– Net result: disinhibition of thalamus
• Huntington’s disease
– Choreiform movements
– Degeneration of striatum
• Initially neurons of indirect pathway more affected with
resultant inhibition of subthalamic nucleus
– Net result: disinhibition of thalamus