The Basal Ganglia

The Basal Ganglia

Outline
* Components of the basal ganglia
* Arrangement of basal ganglia components in the brain
* Architecture: cytology & neurochemistry
* Pathways & circuitry
* Function(s) of the basal ganglia
* Dysfunction and pathology
* Differences between human and rodent basal ganglia?

What are the Basal Ganglia?
The basal ganglia include…
* Neostriatum
o Caudate nucleus
o Putamen
o Nucleus Accumbens
* Globus Pallidus
o Internal segment
o External segment
o Ventral pallidum
* Subthalamic nucleus
* Substantia nigra
o Pars compacta
o Pars reticulata
* Pedunculopontine nucleus**
Subgroups of the basal ganglia
* Striatum
o Caudate nucleus
o Putamen
* Lenticular nuclei
o Globus pallidus
o Putamen
* Corpus striatum
o Caudate
o Lenticular nuclei

How are the basal ganglia arranged in the brain?
Caudate Nucleus
o C shaped structure
o Lateral wall of lateral ventricle
o Head, body and tail of caudate

Putamen and Globus Pallidus
* Putamen + Globus Pallidus = lentiform or lenticular nuclei
* Fills in space between the inferior horn and the anterior horn and body of the lateral ventricle.
* Gap between the lentiform nuclei and the lateral ventricle filled by the caudate nucleus.
* The posterior limb of the internal capsule separates the lentiform nuclei from the thalamus.

* Claustrum
* Septum pellucidum
* Insular cortex
* Corpus callosum
* Caudate nucleus
* Putamen
* Nucleus accumbens
* Internal capsule
* External capsule
* Extreme capsule
* Caudate nucleus
* Putamen
* Globus pallidus external (GPe)
* Globus pallidus internal (GPi)
* Ventral pallidum
* Anterior commissure
* Substantia innominata
* Internal capsule
* Lentiform nucleus**
* Caudate (Head, body, tail)
* Putamen
* GPe & GPi
* Lateral ventricle, anterior and temporal horn
* Internal capsule, anterior and posterior horn
* Caudate nucleus (body and tail)
* Putamen
* Globus pallidus
* Subthalamic nucleus
* Substantia nigra

- Pars compacta
- Pars reticulata
* Subthalamic nucleus
* Substantia nigra
* Globus pallidus external
* Subthalamic nucleus
* Substantia nigra
* Ventral tegmental area

Functions of the Basal Ganglia
* Extrapyramidal motor system
* Motor planning, sequencing and learning
* Striatal neuronal activity is not sufficiently explained by the stimuli presented or the movements performed
* Dependent on certain behavioral situations, certain conditions or particularly types of trials
+ -sensory stimuli but only when they elicit movements
+ -instruction cues (go-no go)
+ -memory related cues
+ -reward (especially ventral striatum)
+ -self-initiated moves
* Basal ganglia distinguished from cerebellum by connections with limbic system

Architecture of the basal ganglia: cellular and neurochemistry

Cytoarchitecture
* Main neurotransmitter in basal ganglia is GABA
* 95% of neurons in neostriatum are medium spiny neurons
o Contain GABA
o Principal neurons: project to globus pallidus and SNpr
o Subpopulations are distinguished by peptides, neurotransmitter receptors and connections
o Receive bulk of afferent input
* Several populations of interneurons
o aspiny
o ACh, somatostatin, GABA/parvalbumin
Neuronal circuitry of the basal ganglia
The Neostriatal Mosaic
* Neostriatum divided into two compartments:
patch (striosome) & matrix
* First described by Ann Graybiel in 1978 using AChE stain
* Not visible in Nissl stains (“hidden chemoarchitecture”)
* Define input/output architecture of neostriatum

Neostriatal Mosaic and Input/Output Organization
* Most inputs to the neostriatum terminate in a patchy fashion (“matrisomes”)
* Input from a given cortical region terminates over an extended anterior-posterior extent
* Functionally related cortical areas project to the same patches
* Output neurons to a given efferent subregion are also arranged in patches
* Neurons in patches project to both GPi/SNpr and GPe

Functional subdivisions
* Sensorimotor
o Putamen + globus pallidus/SNpr
o SNpc
* Association
o Caudate nucleus + globus pallidus/SNpr
o SNpc
* Limbic
o Nucleus accumbens + ventral pallidum
o VTA

Basal ganglia connections and pathways
Connections
* Afferents/inputs (neostriatum):
o Cerebral cortex (entire cortex)
o Thalamus (intralaminar and midline nuclei)
o Amygdala (basolateral nucleus)
o Raphe, substantia nigra pars compacta, VTA
* Efferents/output (GPi, VP, SNpr)
o Ventral tier nuclei of thalamus
o Subthalamic nucleus
o Superior colliculus
Organization of inputs to basal ganglia
Organization of basal ganglia outputs

All regions of cerebral cortex project to the basal ganglia, but output of basal ganglia is directed towards the frontal lobe, particularly pre-motor and supplementary motor cortex
Basic Circuit of Basal Ganglia

Neostriatum
GPi/SNpr
Cerebral Cortex
VA/VL thalamus
Direct vs. indirect pathways
* Different populations of spiny neurons
* Neuromodulators/co-transmitters
* Striosomes vs. matrix
* Dopamine receptor subtypes
Both

Recurrent loops
* Motor loop
o sensorimotor areas 1,2,3,4,5,6 -> putamen -> GP -> VA ->SMA
* Ocularmotor loop
o prefrontal cortex & ppc 9,12, 7 -> caudate -> GP -> VA -> frontal eye fields & SC
* Cognitive loop
o prefrontal cortical areas 9,12 -> caudate -> GP -> VA -> prefrontal cortex
* Limbic loop
o cingulate -> caudate (striosomes)-> GP -> MD -> ant. cingulate.
Topography is maintained within each loop!

Motor loop
Somatotopic subdivisions of the input remain segregated throughout the circuit.
Adapted from Rothwell, 1994; from Alexander and Crutcher, 1990
Processing in the basal ganglia
Huntington’s and Parkinson’s diseases
* Neurodegenerative diseases
* Motor dysfunction
* Brainwide pathology with focus on basal ganglia elements
* Genetic and/or environmental causes
Huntington’s Disease
Clinical symptoms
* Hyperkinetic & hemiballistic movements

Pathology hallmarks
* Striopallidal degeneration
* Decreased striatal volume
* Decrease in 5-HT1B receptors in ventral pallidum
Hyperkinetic hypothesis
* Reduced Glu (+) from STN to GPi, due either to STN lesions or reduced striatopallidal inhibitory influences along the in direct pathway lead to reduced inhibitory outflow from GPi/SNr and excessive disinhibition of the thalamus.
* Increased Glu (+) to cortical areas engaged by the motor circuit (SMA, PMC, MC) results in hyperkinetic movements.
Parkinson’s Disease
Clinical symptoms
* Hypokinetic movement
* Cogwheel rigidity

Pathology hallmarks
* Nigostriatal degeneration
* DA neuronal degeneration in SN
Hypokinetic hypothesis
* Inhibition of GPe within the indirect pathway leads to disinhibition of the STN
* Increased STN to the basal ganglia output nuclei (Gpi/SNr), leads to excessive thalamic inhibition.
* This is reinforced by reduced inhibitory input to Gpi/SNr through the direct pathway.
* Overall result is a reduction in reinforcing influence of the motor circuit upon cortically initiated movements.

PD Therapeutics: The approaches
* Pharmacology
o DA, mGluR, MAO(B) inhibitors, antioxidants, iron chelators
* Surgical
o Pallidal ablation
o DBS of globus pallidus or STN
* Transplantation
o Fibroblast cells
o Stem cells
* Vaccines
* RNA interference (RNAI)-based treatments

DBS: Deep Brain Stimulation of STN
Common themes in neurodegeneration
* Neurotoxicity
* Inflammation (glia)
* Apoptosis
* Abnormal protein aggregation
Thank you!
Notable differences between basal ganglia of human and rodents …..
There are differences in:
* Divisions & nomenclature
* Proportions
* Topography of afferent and efferent projections
Globus pallidus and entopeduncular nucleus (rodent)
vs.
Globus pallidus (external) and Globus pallidus (internal) (primate)
Regional proportion by volume
(% of total volume)
Spinal Cord

Major projection differences

* Neurons projecting to the motor and associative striatum
o Rats: reside in distinct regions
o Primates: arranged in interdigitating clusters.
* Terminal fields of projections arising from the motor and associative striatum
o rats: largely segregated
o Primates: not segregated
* Organization of patch- and matrix-projecting dopamine cells
o Rats: organized in spatially, morphologically, and histochemically distinct ventral and dorsal tiers,
o Primates: no (bi)division of the dopaminergic system that results in two areas which have all the characteristics of the two tiers in rats.

The Basal Ganglia.ppt
http://login.ncmir.ucsd.edThe Basal Ganglia

Outline
* Components of the basal ganglia
* Arrangement of basal ganglia components in the brain
* Architecture: cytology & neurochemistry
* Pathways & circuitry
* Function(s) of the basal ganglia
* Dysfunction and pathology
* Differences between human and rodent basal ganglia?

What are the Basal Ganglia?
The basal ganglia include…
* Neostriatum
o Caudate nucleus
o Putamen
o Nucleus Accumbens
* Globus Pallidus
o Internal segment
o External segment
o Ventral pallidum
* Subthalamic nucleus
* Substantia nigra
o Pars compacta
o Pars reticulata
* Pedunculopontine nucleus**
Subgroups of the basal ganglia
* Striatum
o Caudate nucleus
o Putamen
* Lenticular nuclei
o Globus pallidus
o Putamen
* Corpus striatum
o Caudate
o Lenticular nuclei

How are the basal ganglia arranged in the brain?
Caudate Nucleus
o C shaped structure
o Lateral wall of lateral ventricle
o Head, body and tail of caudate

Putamen and Globus Pallidus
* Putamen + Globus Pallidus = lentiform or lenticular nuclei
* Fills in space between the inferior horn and the anterior horn and body of the lateral ventricle.
* Gap between the lentiform nuclei and the lateral ventricle filled by the caudate nucleus.
* The posterior limb of the internal capsule separates the lentiform nuclei from the thalamus.

* Claustrum
* Septum pellucidum
* Insular cortex
* Corpus callosum
* Caudate nucleus
* Putamen
* Nucleus accumbens
* Internal capsule
* External capsule
* Extreme capsule
* Caudate nucleus
* Putamen
* Globus pallidus external (GPe)
* Globus pallidus internal (GPi)
* Ventral pallidum
* Anterior commissure
* Substantia innominata
* Internal capsule
* Lentiform nucleus**
* Caudate (Head, body, tail)
* Putamen
* GPe & GPi
* Lateral ventricle, anterior and temporal horn
* Internal capsule, anterior and posterior horn
* Caudate nucleus (body and tail)
* Putamen
* Globus pallidus
* Subthalamic nucleus
* Substantia nigra

- Pars compacta
- Pars reticulata
* Subthalamic nucleus
* Substantia nigra
* Globus pallidus external
* Subthalamic nucleus
* Substantia nigra
* Ventral tegmental area

Functions of the Basal Ganglia
* Extrapyramidal motor system
* Motor planning, sequencing and learning
* Striatal neuronal activity is not sufficiently explained by the stimuli presented or the movements performed
* Dependent on certain behavioral situations, certain conditions or particularly types of trials
+ -sensory stimuli but only when they elicit movements
+ -instruction cues (go-no go)
+ -memory related cues
+ -reward (especially ventral striatum)
+ -self-initiated moves
* Basal ganglia distinguished from cerebellum by connections with limbic system

Architecture of the basal ganglia: cellular and neurochemistry

Cytoarchitecture
* Main neurotransmitter in basal ganglia is GABA
* 95% of neurons in neostriatum are medium spiny neurons
o Contain GABA
o Principal neurons: project to globus pallidus and SNpr
o Subpopulations are distinguished by peptides, neurotransmitter receptors and connections
o Receive bulk of afferent input
* Several populations of interneurons
o aspiny
o ACh, somatostatin, GABA/parvalbumin
Neuronal circuitry of the basal ganglia
The Neostriatal Mosaic
* Neostriatum divided into two compartments:
patch (striosome) & matrix
* First described by Ann Graybiel in 1978 using AChE stain
* Not visible in Nissl stains (“hidden chemoarchitecture”)
* Define input/output architecture of neostriatum

Neostriatal Mosaic and Input/Output Organization
* Most inputs to the neostriatum terminate in a patchy fashion (“matrisomes”)
* Input from a given cortical region terminates over an extended anterior-posterior extent
* Functionally related cortical areas project to the same patches
* Output neurons to a given efferent subregion are also arranged in patches
* Neurons in patches project to both GPi/SNpr and GPe

Functional subdivisions
* Sensorimotor
o Putamen + globus pallidus/SNpr
o SNpc
* Association
o Caudate nucleus + globus pallidus/SNpr
o SNpc
* Limbic
o Nucleus accumbens + ventral pallidum
o VTA

Basal ganglia connections and pathways
Connections
* Afferents/inputs (neostriatum):
o Cerebral cortex (entire cortex)
o Thalamus (intralaminar and midline nuclei)
o Amygdala (basolateral nucleus)
o Raphe, substantia nigra pars compacta, VTA
* Efferents/output (GPi, VP, SNpr)
o Ventral tier nuclei of thalamus
o Subthalamic nucleus
o Superior colliculus
Organization of inputs to basal ganglia
Organization of basal ganglia outputs

All regions of cerebral cortex project to the basal ganglia, but output of basal ganglia is directed towards the frontal lobe, particularly pre-motor and supplementary motor cortex
Basic Circuit of Basal Ganglia

Neostriatum
GPi/SNpr
Cerebral Cortex
VA/VL thalamus
Direct vs. indirect pathways
* Different populations of spiny neurons
* Neuromodulators/co-transmitters
* Striosomes vs. matrix
* Dopamine receptor subtypes
Both

Recurrent loops
* Motor loop
o sensorimotor areas 1,2,3,4,5,6 -> putamen -> GP -> VA ->SMA
* Ocularmotor loop
o prefrontal cortex & ppc 9,12, 7 -> caudate -> GP -> VA -> frontal eye fields & SC
* Cognitive loop
o prefrontal cortical areas 9,12 -> caudate -> GP -> VA -> prefrontal cortex
* Limbic loop
o cingulate -> caudate (striosomes)-> GP -> MD -> ant. cingulate.
Topography is maintained within each loop!

Motor loop
Somatotopic subdivisions of the input remain segregated throughout the circuit.
Adapted from Rothwell, 1994; from Alexander and Crutcher, 1990
Processing in the basal ganglia
Huntington’s and Parkinson’s diseases
* Neurodegenerative diseases
* Motor dysfunction
* Brainwide pathology with focus on basal ganglia elements
* Genetic and/or environmental causes
Huntington’s Disease
Clinical symptoms
* Hyperkinetic & hemiballistic movements

Pathology hallmarks
* Striopallidal degeneration
* Decreased striatal volume
* Decrease in 5-HT1B receptors in ventral pallidum
Hyperkinetic hypothesis
* Reduced Glu (+) from STN to GPi, due either to STN lesions or reduced striatopallidal inhibitory influences along the in direct pathway lead to reduced inhibitory outflow from GPi/SNr and excessive disinhibition of the thalamus.
* Increased Glu (+) to cortical areas engaged by the motor circuit (SMA, PMC, MC) results in hyperkinetic movements.
Parkinson’s Disease
Clinical symptoms
* Hypokinetic movement
* Cogwheel rigidity

Pathology hallmarks
* Nigostriatal degeneration
* DA neuronal degeneration in SN
Hypokinetic hypothesis
* Inhibition of GPe within the indirect pathway leads to disinhibition of the STN
* Increased STN to the basal ganglia output nuclei (Gpi/SNr), leads to excessive thalamic inhibition.
* This is reinforced by reduced inhibitory input to Gpi/SNr through the direct pathway.
* Overall result is a reduction in reinforcing influence of the motor circuit upon cortically initiated movements.

PD Therapeutics: The approaches
* Pharmacology
o DA, mGluR, MAO(B) inhibitors, antioxidants, iron chelators
* Surgical
o Pallidal ablation
o DBS of globus pallidus or STN
* Transplantation
o Fibroblast cells
o Stem cells
* Vaccines
* RNA interference (RNAI)-based treatments

DBS: Deep Brain Stimulation of STN
Common themes in neurodegeneration
* Neurotoxicity
* Inflammation (glia)
* Apoptosis
* Abnormal protein aggregation
Thank you!
Notable differences between basal ganglia of human and rodents …..
There are differences in:
* Divisions & nomenclature
* Proportions
* Topography of afferent and efferent projections
Globus pallidus and entopeduncular nucleus (rodent)
vs.
Globus pallidus (external) and Globus pallidus (internal) (primate)
Regional proportion by volume
(% of total volume)
Spinal Cord

Major projection differences

* Neurons projecting to the motor and associative striatum
o Rats: reside in distinct regions
o Primates: arranged in interdigitating clusters.
* Terminal fields of projections arising from the motor and associative striatum
o rats: largely segregated
o Primates: not segregated
* Organization of patch- and matrix-projecting dopamine cells
o Rats: organized in spatially, morphologically, and histochemically distinct ventral and dorsal tiers,
o Primates: no (bi)division of the dopaminergic system that results in two areas which have all the characteristics of the two tiers in rats.

The Basal Ganglia.ppt

Read more...

Anxiety Disorders

Anxiety Disorders

* Panic disorder
o Can be induced by lactate or CO2 in PD sufferers (only occasionally in normal people)
o Increased activity in parahippocampal gyrus,
o Decreased activity in anterior temporal cortex & amygdala (seems odd!)
o May have 3, rather than 2, repeats of a section on chromosome 15
+ Also have joint laxity (bend too far)

* Treatments for panic disorder
o Benzodiazepines (e.g., Valium)
+ Increase frequency of Cl- channel openings in response to GABA
+ Have little or no effect alone: safer than barbiturates
+ Allopregnanolone = endogenous agonist at benzodiazepine binding site.
o Buspirone (Buspar): 5-HT1a agonist (GI/O)
o SSRIs: fluoxetine (Prozac), paroxetine (Paxil)

Benzodiazepine receptors in brain
PTSD
* Monozygotic > dizogotic concordance
o Genetics 1/3 of variance
* NMDA mechanisms in amygdala
o May mediate both the conditioning and the extinction
+ NMDA antagonists in amygdala prevent extinction
+ Hippocampus and PFC also lose effectiveness in extinction
* Not due to high levels of glucocorticoids:
o Usually PTSD sufferers have LOWER than normal cortisol levels, despite high CRH
+ Maybe it’s the high CRH that  symptoms
+ Or maybe it’s increased responsiveness to CRH or cortisol
* Individual differences in responsiveness to trauma
* Sometimes treated with β NE antagonists (propranolol) or protein synthesis inhibitors soon after the trauma or during recall of the trauma
OCD
* Increased metabolism in orbitofrontal cortex, cingulate, and caudate nuclei.
* Decreased REM latency (~ to depression)
* At least 2 gene polymorphisms:
o For BDNF, 5-HT2A receptor
* Treatment: SSRIs
Cingulotomy to treat OCD
Tourette’s Syndrome
* In many ways opposite Parkinson’s disease
* Treated with dopamine antagonists
* Monozygotic concordance: 53-77%; dizygotic concordance: 8-23%
* Witty Ticcy Ray (by Oliver Sacks): “We Touretters…are forced into levity by our Tourette’s and forced into gravity when we take Haldol….You have a natural balance: we must make the best of an artificial balance.”

THE NIGROSTRIATAL AND MESOLIMBIC DOPAMINE SYSTEMS
* Nigrostriatal and mesolimbic tracts are parallel.
o Begin in midbrain (substantia nigra & ventral tegmental area, VTA)
o End in dorsal (caudate & putamen) and ventral (N. accumbens) striatum
o Cortico-striato-pallido-thalamic-cortical loops

Nigrostriatal system
* Plans and triggers self-initiated movements
* Adjusts posture
* Degeneration  Parkinson’s disease
o Tremor at rest
o Difficulty initiating movements

Mesolimbic system
* Increases responsiveness to external and internal stimuli
* Motivation
* Motor activity
* Reward
* Drug addiction
* Schizophrenia
Nigrostriatal dopamine tract
Mesolimbic dopamine tract

Direct pathway
* Positive feedback loop
* Cortical areas that initiated the activity are further excited.
* 2 consecutive inhibitory influences
* Then an excitatory influence
* Stimulating the first inhibitory path inhibits the second inhibitory path: disinhibits the excitatory path.

Sensorimotor Cortex
Striatum
Direct pathway
* Stimulate putamen
* Inhibits GPi/SNr
via D1 receptors
Sensorimotor Cortex
Striatum
Direct Pathway
When putamen inhibits
GPi/SNr, VL/VA
is disinhibited.
Thus, VL/VA excites
sensory motor cortex.
Indirect Pathway
Negative feedback
Begins with 2
inhibitory paths:
1. Putamen to GPe
2. GPe to STN
Sensorimotor Cortex
Indirect Pathway
Those inhibitory paths disinhibit an excitatory path.
But that exc. path ends on another inhibitory path!
Function
* Direct path excites cortex; indirect path inhibits it: opposing functions.
* May “sharpen” influence on behavior
o (similar to “sharpening” receptive fields).
* May provide greater control over movement
o (similar to having both EPSPs and IPSPs on same neuron).

Effects of Dopamine
* D1 receptors excite the Direct Pathway
o (i.e., increase excitation of the cortex).
* D2 receptors inhibit the Indirect Pathway
o (i.e., decrease the inhibition of thalamus and therefore increase excitation of cortex).
* Therefore, both effects increase excitation of cortex
o (i.e., increase either movement or motivation).

The Mesolimbic System
* Circuit is parallel to nigrostriatal system:
o Direct and indirect pathways
o Prefrontal cortex vs. sensory motor
o N. accumbens (ventral striatum), vs. caudate & putamen (dorsal striatum)
o Ventral pallidum vs. GPi and GPe
o Mediodorsal thalamus vs. VL/VA
Prefrontal Cortex
VP normally inhibits

Effects of Dopamine
* D1 receptors excite the Direct Pathway
o (i.e., increase excitation of the cortex).
* D2 receptors inhibit the Indirect Pathway
o (i.e., decrease the inhibition of thalamus and therefore increase excitation of cortex).
* Therefore, both effects increase excitation of cortex
o (i.e., increase either movement or motivation).

Glutamate/DA balance in schizophrenia
* Cortical or hippocampal hypofunction may  decrease glutamate in NAcc and striatum
* decrease tonic DA release
* increase DA receptor sensitivity
* hyperresponsive to phasic input

Anxiety Disorders.ppt

Read more...

Movement Disorders

Movement Disorders

* Background
o AKA Extrapyramidal Disorders
o These disorders impair the regulation of voluntary motor activity w/o affecting the strength, sensation, or cerebellar fcn.
o Result from dysfunction of the basal ganglia
+ Caudate
+ Putamen
+ Globus Pallidus
+ Subthalamic Nucleus
+ Substantia Nigra
+ Lentiform Nucleus
# Putamen & Globus Pallidus
+ Corpus Striatum
# Lentiform Nucleus + Caudate Nucleus
* Basal Ganglia Circuitry (Fig 7-1)
o Corticocortical Loop:
Cerebral Cortex
Caudate & Putamen
Internal Segment
Globus Pallidus
Thalamus
* Basal Ganglia Circuitry (Fig 7-1)
o Nigrostriatal Loop:
Substantia Nigra
Caudate & Putamen
* Basal Ganglia Circuitry (Fig 7-1)
o Striatalpallidal Loop:
Caudate & Putamen
External Segment
Globus Pallidus
Subthalamic Nuclei
Internal Segment
Globus Pallidus
* Types of Abnormal Movements
o Tremor: rhythmic movement characterized by when it occurs
+ Postural Tremor
# During sustained posture
+ Intention Tremor
# During movement; absent at rest
+ Resting Tremor
# At rest
o Chorea: irregular muscle jerks
+ Florid Cases
# Fully developed
# Forceful movements of limbs, head, facial grimacing, & tongue movements
+ Mild Cases
# Characterized by:
* Clumsiness
* Milkmaid grasp
* Absent in sleep
o Hemiballismus
+ Unilateral Chorea
+ Involves the proximal muscles
+ Vascular disease of contralateral subthalamic nucleus
o Athetosis
+ Continued slow, sinuous, & writhing movements
o Dystonia: sustained athetotic movements
+ Segmental Dystonia
# Affects one or more limbs
+ Focal Dystonia
# Affects localized muscle groups
+ Palliative/Provocative
+ Causes
o Myoclonus
+ Definition
+ Classification
+ Generalized: widespread
# Physiological
# Essential
# Epileptic
# Symptomatic
+ Segmental: more localized
o Tics
+ Definition
+ Palliative/Provocative
+ Types
# Transient Simple: common in children, resolve w/I 1 yr
# Chronic: any age, no tx
# Persistent Simple or Multiple: onset before 15 yoa, resolve in adults
# Chronic Multiple: Tourette’s Sydrome
* Hypokinetic Movement Disorders
o Parkinson’s Disease
* Hyperkinetic Movement Disorders
o Huntington’s Disease
o Wilson’s Disease
o Tourette’s Syndrome
o Restless Leg Syndrome
* Parkinson’s Disease - Hypokinetic
o Defined as a syndrome consisting of variable combination of tremor, rigidity, bradykinesia, and characteristic disturbance of gait and posture
o Onset: mid-late life; mean age is 57 yrs
o Epidemiology:
+ Affects all ethnicities
+ has equal M/F distribution
+ occurs 1-2 per 1,000 people in general population
+ occurs 1 per 100 people that are over 65 yrs
+ 4th most common disease in the elderly
* Parkinson’s Disease - Hypokinetic
o Cause: unknown
o Pathophysiology:
+ Loss of dopaminergic cells in the substantia nigra
# Dopamine’s normal function
+ Over excitation of the caudate & putamen
+ Over excitation of the corticospinal tracts
+ Oscilation of feedback
+ Decrease in thalamic excitation of the motor cortex
o Four Hallmark Signs
+ Resting Tremor (Pill-Rolling)
+ Rigidity (Lead-Pipe or Cogwheel)
+ Bradykinesia
+ Flexed Posture with shuffling gait (Festinating)
o Examination:
+ History
+ Phsyical Findings:
# Passive movement
# Muscle Strength
# Sensory
# Deep Tendon Reflexes
# Autonomic
# Myerson’s Sign
# Pull Test
o Diagnosis:
+ Four Hallmark signs
+ Tremor is absent in 30% of patients
o Differential Diagnosis
+ Involuntary tremor vs. Intentional tremor
+ Depression
+ Wilson’s Disease
+ Huntington’s Disease
o A neurodegenerative disorder which predominately has behavioral, cognitive, or signs
o Onset: Usually begins during adult life
o Epidemiology:
+ 5-10 per 100,000 in the US
+ 50% chance to pass on the disorder
+ Anticipation
+ Paternal Descent
* Huntington’s Disease – Hyperkinetic
o Cause: Autosomal Dominant Disorder
o Pathophysiology:
+ Mutation on chromosome 4: CAG repeats
+ CAG Normal Function: codes for glutamine
+ Over-expression of the gene: i.e. excess glutamine
+ Uncertainty?
* Huntington’s Disease – Hyperkinetic
o Cause: Autosomal Dominant Disorder
o Pathophysiology:
+ Pathological Changes
# Atrophy & neuronal degeneration of cortex
# Hallmark: caudate atrophy
+ Projected Conclusion?
# Over activity
# Under activity
o Examination:
+ Physical Findings
# Initial Findings
* Gradual onset
* Slowed saccadic movements 1st sign
* In 85% chorea is predominate movement disorder
# Juvenile Form
* AKA The Westphal Variant
* Rigidity & bradykinesia
* Tremors, Dystonic postures, & Ataxia
* Mental retardation, Seizures, & myoclonus
o Examination:
+ Physical Findings
# Adult Onset
* Prominent chorea
* Bradykinesia
* Postural reflex compromise
# Terminal Phase
* Dysarthria, dysphagia, & respiratory difficulties
# General
* Cognitive impairment
* Depression
* Psychiatric disorders
* Wilson’s Disease – Hyperkinetic
o Onset
+ Hepatic Dysfunction – 11 yoa
+ Neurological Dysfunction – 19 yoa
o Epidemiology
+ Rare
+ 1 in 40,000 people
o Cause: Autosomal Recessive Disorder
o Pathophysiology
+ Abnormal copper metabolism
+ Deposition of copper in tissues
o Examination
+ Physical Findings
# Children: hepatic dysfunction predominates
* Sardonic Smile
* Behavioral problems
# Adults: neurological dysfunction predominates
* Parkinsonian features
# General
* Hallmark: Kayser-Fleischer Rings
* 1/3 experience psychiatric symptoms
* Other ocular abnormalities
* Gilles de la Tourette Syndrome – Hyperkinetic
o Diagnosed when childhood onset tics are multifocal, motor or vocal, lasting longer than 1 yr and naturally wax and wane
o Cause: unknown
o Onset: 2-21 yoa
o Male predilection
* Gilles de la Tourette Syndrome – Hyperkinetic
o Examination
+ Physical Findings
# Simple Tics
* Motor: blinking, facial grimacing, shoulder shrugging
* Vocal: throat clearing, grunting, snorting, barking
# Complex Tics
* Motor: hopping, skipping, Echopraxia
* Vocal: Coprolalia, Echolalia, Palilalia
* Restless Legs Syndrome – Hyperkinetic
o Common movement disorder
o Diagnostic Criteria
# Desire to move limbs which is associated with unpleasant sensations
# Restlessness
# Worsening of symptoms @ rest w/ temporary relief w/ movement
# Worsening of symptoms @ night
* Restless Legs Syndrome – Hyperkinetic
o Common Descriptions
+ Always unpleasant, but not necessarily painful
+ Need to move
+ Crawling
+ Tingling
+ Itching
+ Restless

Movement Disorders.ppt

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