Basal Ganglia

Motor output from Sustantia Nigra pars reticulata

conveys information from head and neck

Motor output from Globus Pallidus

conveys infromation from the rest of the body

Oculomotor channel: sources of cortical input

posterior parietal cortex; prefrontal cortex

Huntington's progression

slow progression

Main structures of Basal Ganglia

1. Caudate Nucleus 2. Putamen 3. Globus Pallidus 4. Subthalamic Nucleus of Luys 5. Substantia Nigra

Four main sources of input to the Basal Ganglia

1. Cerebral Cortex 2. Substantia Nigra pars Compacta (SNc) 3. Thalamus 4. Raphe Nucleus

Two main pathways of intrinsic Basal Ganglia connections

1. Direct pathway 2. Indirect pathway

Two segments of Globus Pallidus

1. Internal Segment/Medial 2. External Segment/Lateral

Parallel Channels through Basal Ganglia

1. Motor channel 2. Oculomotor channel 3. Prefrontal channel 4. Limbic channel

Classic triad of Parkinson's

1. Resting tremor 2. Bradykinesia 3. Cogwheel rigidity accompanied by postural instability that causes an unsteady gait

Output from internal segment of Globus Pallidus and Substantia Nigra pars reticulata gets sent to what structures

1. Thalamic Nuclei: - Ventral Anterior Nucleus - Ventral Lateral Nucleus - CentreMedian/Parafasicular Nucleus - Dorsomedial N. (impt, re: limbic pathways) 2. Reticular Formation in Pons and Medulla

Olivopontocerebellar atrophy

Characterized by parkinsonism together with ataxia

Treatment of hemiballismus

Dopaminergic antagonists such as haloperidol

Genetic anticipation

Earlier onset of disease in each successive generation

Basal Ganglia is apart of what system

Extrapyramidal motor system

Oculomotor channel: Cortical targets of outputs

Frontal eye fields; supplementary eye fields

Workhorses of Nervous System

GABA and Glutamate

Indirect pathway in the intrinsic Basal Ganglia connections

Globus Pallidus external segment---> Subthalamic Nucleus of Luys ----> Globus Pallidus internal segment or Substantia Nigra pars reticulata

Motor channel: basal ganglia output nuclei

Globus Pallidus internal segment and Substantia Nigra pars reticulata

Oculomotor channel: Basal Ganglia output nuclei

Globus Pallidus internal segment and Substantia Nigra pars reticulata

Prefrontal channel: Basal Ganglia output nuclei

Globus Pallidus internal segment and Substantia Nigra pars reticulata

GABA is synthesized from what neurotransmitter

Glutamate

Classic cause of hemiballismus

Lacunar infarct of the subthalamic nucleus of Luys which leads to decreased pallidal inhibition of the thalamus

Most effective drug for treatment of Parkinson's

Levodopa plus carbidopa

Anteropulsion

- A continual appearance of falling and shuffling forward

Progressive Supranuclear Palsy

- Also called Steele-Richardson-Olszewski syndrome - Degeneration of Superior Colliculus, Red nucleus, dentate nucleus, subthalamic nucleus, and globus pallidus - Range of vertical eye movement is markedly limited

Pill-rolling tremor

- Assymmetrical and involves mainly the hands and upper extremities - Rolling something between their thumb and other fingers

Striatum

- Caudate Nucleus + Putamen - Receives all inputs to the basal ganglia

Atypical Parkinsonism

- Differs from idiopathic Parkinson's disease by having relatively symmetical symptoms, absence of resting tremor, early appearance of postural instability, and little response to dopaminergic agents

End result of cortical input via Direct Pathway

- Excitation of Thalamic Nuclei - Facilitates movement through its connections with motor and pre-motor cortex

Basal Ganglia Input from Cerebral Cortex

- Excitatory - Most input from cortex uses glutamate as neurotransmitter

Internal Capsule

- Fiber system - Separates the Caudate and the Putamen - Caudate and Putamen continues to exchange info via cellular bridges

Cortical basal degeneration

- Has parkinsonism - Plus limb dystonia and marked cortical features such as apraxia and wandering or alien limb syndrome

Bradykinesia and hypokinesia examples in Parkinson's

- Hypomimia/masked faces - Decrease in spontaneous blink rate - Hypophonic voice - Slow saccades - Micrographia - Stooped posture - Postural instability, the diminished ability to make reflex postural adjustments - Diminished arm swing

Huntington's Disease genetics

- Inherited autosomal dominant genetic condition that results in expanded trinucleotide repeats and progressive neurodegeneration - Gene is on Chromosome 4 - Individuals with over 40 CAG repeats either have Huntington's disease or will ultimately develop it. The higher the number of repeats, the younger the onset

End result of cortical input via Indirect Pathway

- Inhibition of Thalamic Nuclei - Inhibits movement through its connections back to the cortex

Striatonigral Degeneration

- Loss of dopaminergic neruons of the substantia nigra pars compacta, globus pallidus, and substantia nigra pars reticulata - Atypical parkinsonism is often present

Shy-Drager Syndrome

- Marked atrophy of the intermediolateral cell column of the spinal cord - Parkinsonism plus autonomic disturbances usch as marked orthostatic hypotension, impotence, and urinary incontinence

Limbic channel: Thalamic relay nuclei

Mediodorsal and ventral anterior nuclei

Psychiatric symptoms Huntington's

- May precede motor or cogntive symptoms in persons unaware that they have HD gene - Most common pyschiatric problems: depression, anxiety, impulsivity, OCD-like symptoms, psychosis

Input from Substantia Nigra pars Compacta

- Nigrostriatal Pathway uses DA as its neurotransmitter - Excitatory and inhibitory neurotransmitter to other neurons

Festinating gait

- Once walking starts - Walk with small shuffling steps

Wilson's disease

- Parkinsonian symptoms can also cause tremor, rigidity, and bradykinesia

Retropulsion

- Pulled backward slightly - Take several backward steps to regain balance or may fall

Machado-Joseph disease and dentatorubropallidoluysian atrophy

- Rare neurodegenerative disorders that often include parkinsonian features - Transmitted by autosomal dominant inheritance - Caused by expanded trinucleotide repeats

Lesions to Basal Ganglia

- Result in hyperkinetic movement disorders (e.g. Huntington's Disease) or hypokinetic movement disorders (e.g. Parkinson's Disease) - Also have cognitive function

Multisystem Atrophy Disorders

- Striatonigral degeneration - Shy-Drager syndrome - Olivopontocerebellar atrophy

Huntington's disease

- Trinucleotide repeat disorder - Presents with predominantly parkinsonian features in the unusual patient in which the onset is in childhood or early adulthood

On-off phenomenon

- With advanced Parkinson's - Fluctuation between dyskinesia and immobility with very little functional time

Dementia with Lewy Bodies

- important cause of parkinsonism and dementia - accompanied by prominent psychiatric symtoms

Pathological signs of Parkinson's

- loss of pigmented dopaminergic neurons in the substantia nigra pars compacta - Remaining dopaminergic neurons often contain characteristic cytoplasmic inclusions--- Lewy bodies

Striatum receives most of incoming info from what

The telencephalic Basal Ganglia

What percent of individuals over age 65 have parkinson's

1%

Oculomotor channel: Basal Ganglia input nuclei

Caudate, body

Prefrontal channel: Basal Ganglia input nuclei

Caudate, head

Dorsal Striatal pathway

The first three channels together

Huntington's prevalence

4.5 cases/100,00 people except in specific areas in Venezuela its 50/50

Usual age of onset of Parkinson's

40-70 years

Huntington's death

About 20 years post onset of symptoms

Basal Ganglia influences what

Activity of the descending motor systems

Limbic channel: cortical targets of output

Anterior cingulate; orbital frontal cortex

Medication causes of Parkinsonism

Antipsychotic and antiemetic dopaminergic antagonists can cause rigidity and hypokinesia Onset is usually abrupt and symptoms are symmetrical

What Basal Ganglia structure receives the most input

Caudate + Putamen Receives input from other structures and then sends to the rest of the Basal Ganglia

Huntington's pathology

Hallmark is progressive atrophy of the striatum, especially involving he caudate nucleus

Cause of Parkinson's Disease

Idiopathic

Discovery of Huntington's gene

In 1993 by Nancy Wexler using genetic material from affected persons in Maracaibo Venezuala

Myerson's sign

Inability to suppress blinking when the center of the brow ridge is tapped repeatedly

Two structures responsible for output from Basal Ganglia

Inhibitory 1. Internal segment of Globus Pallidus 2. Substantia Nigra pars reticulata Use GABA

Glycine

Inhibitory neurotransmitter, particularly in the Spinal Cord and brainstem

Ventral Striatal pathway

The fourth channel

Glutamate

Most abundant excitatory neurotransmitter in the nervous system

GABA

Most abundant inhibitory neurotransmitter in the nervous system

Input from Intralaminar Thalamic Nucleus

Most important input comes from CentreMedian/Parafasicular nucleus

Limbic channel: Basal Ganglia input nuclei

Nucelus accumbens ; ventral caudate; ventral putamen

Periods of freezing in Parkinson's

Occurs during the wearing off of medications when the person becomes unable to move

Other locations of lesions of hemiballismus

Other regions of the basal ganglia, especially the striatum

Common causes of Huntington's death

Pneumonia, heart disease, suicide

Prefrontal channel: Sources of cortical input

Posterior parietal cortex; premotor cortex

Prefrontal channel: Cortical targets of output

Prefrontal cortex

Input from Raphe Nucleus

Provides serotonin to Basal Ganglia

Motor channel: basal ganglia input nuclei

Putamen

Parkinsonism plus syndromes

Several neurodegenerative conditions are associated with parkinsonism Produce atypical parkinsonism

Motor channel: sources of cortical input

Somatosensory cortex; primary motor cortex; premotor cortex

What movements typically follow hemiballismus

Sublter choreoathetotic movements

Other output from from Substantia Nigra pars reticulata

Superior Coliculus and influences Tectospinal tract

Motor channel: Cortical target of output

Supplementary motor area; premotor cortex; primary motor cortex

Limbic channel: Sources of cortical input

Temporal cortex; hippocampus; amygdala

Direct pathway in the intrinsic Basal Ganglia

Travels from striatum directly to internal Globus Pallidus or to the Substantia Nigra pars reticulata

En bloc turning

Turns are executed without the normal twist of the torso

Hemiballismus Clinical presentation

Unilateral flinging movements of the extremities contralateral to a lesion in the basal ganglia

Additional causes of hemiballismus

Unilateral lesions of the basal ganglia such as hemorrhage, tumor, infectoin or inflammation

Lateralization of movement

Unilaterl but later becomes bilateral, although the severity often remains asymmetrical

Huntington's onset

Usually between 30-50 years of age.

Progression of Parkinson's

Usually insidious over the course of 5-15 years

Oculomotor channel: Thalamic relay nuclei

Ventral Anterior Nucleus and Mediodorsal

Prefrontal channel: Thalamic relay nuclei

Ventral Anterior Nucleus and Mediodorsal Nucleus

Motor channel: Thalamic relay nuceli

Ventral Lateral and Ventral Anterior

Limbic channel: Basal Ganglia output nuclei

Ventral pallidum; Globus Pallidus internal segment; Substantia Nigra pars reticulata

Huntington's onset

insidious

Huntington's affects

movement, cognition, emotional/psychiatric functioning