Parkinson's Disease and Basal Ganglia Disorders

What is the basal ganglia?

Collection of gray matter nuclei located deep within white matter of the cerebral hemispheres.

What are the components of the basal ganglia?

Striatum: caudate nucleus and putamen

Globus pallidus

Subthalamic nucleus

Substantia nigra

What is the function of the basal ganglia?

Selecting and maintaining purposeful motor activity while suppressing unwanted or useless movement.

Helping monitor and coordinate slow, sustained contractions related to posture and support.

Inhibiting muscle tone throughout the body (proper muscle tone is normally maintained through a balance of excitatory and inhibitory inputs to the neurons that innervate skeletal muscle)

What does the corpus striatum receive?

Excitatory input from several areas of the cerebral cortex as well as inhibitory and excitatory input from the dopaminergic cells of the substantia nigra.

Which dopamine receptor is excitatory and which in inhibitory?

D1: dopamine excitatory

D2: dopamine inhibitory

Describe the direct pathway of the basal ganglia (without dopamine)

Brain to body of caudate nucleus which causes excitation and then goes back to brain.

Describe the indirect pathway of the basal ganglia (without dopamine)

Comes from motor cortex, hits the body of the caudate nucleus, goes to the thalamus and results in an inhibitory response to the brain.

Describe the direct pathway of the basal ganglia (with dopamine)

D1 receptors work on the pathway, and the main goal is to cause excitation by the time they reach the end of the pathway.

Describe the indirect pathway of the basal ganglia (with dopamine)

D2 receptors work on the pathway, they cancel out what is going on in the pathway and also result in excitation.

What happens if there is an issue with ACh?

There will be signs of a movement disorder either hypo or hyperactivity.

List the movement orders from slow to fast

Bradykinesia, hypokinesia

Rigidity

Dystonia

Athetosis

Chorea

Ballismus

Tics

Myoclonus

Tremor (can be fast or slow)

What are the 2 types of rigidity?

Cogwheeling, where you move the muscle slowly and it feels like its clicking all the way down (jerky movements)

Lead-pipe rigidity, where at first the muscle is stiff and hard to move but with sustained pulling it releases down)

What is the difference between spasticity and rigidity?

Spasticity is an UMN sign, so you will see other UMN signs with it. Rigidity will not have these other findings.

What occurs in a unilateral basal ganglia lesion?

The movement disorder is contralateral to the lesion

What is dystonia?

Co-contraction of agonist and antagonist muscles.

Focal examples are torticollis (cervical dystonia), blepharospasm, spasmodic dysphonia

What is athetosis?

Sinuous writhing movements of hands and fingers. Can be seen in patients who are having side effects from Parkinson's disease meds.

What is chorea?

Dance-like movements. Seen in rheumatic fever and Huntington's disease.

What is ballismus?

Rapid, flinging quality of movement. Hemi-ballismus is this on one side.

What is a tic?

Sudden brief movement usually preceded by urge to perform.

What is myoclonus?

Rapid muscular jerk, like when you're falling asleep and suddenly jump awake.

What is a tremor?

Rhythmic oscillating movement.

What are the 3 kinds of tremors highlighted?

Resting - Seen in Parkinson's

Postural - Occurs when body part held against gravity (essential tremor)

Intention - Occurs when patient reaches toward a target (cerebellar target, gets worse as they approach the object)

What are the 4 characteristics of Parkinsonism?

Tremor

Rigidity

Akinesia

Postural disturbance

What are some causes of secondary Parkinsonism?

Other neurodegenerative diseases, like progressive supranuclear palsy

Drug effects like neuroleptics, metoclopramide

Toxic effects

What is Parkinson's Disease?

Selective depletion of dopamine-producing neurons in the substantia nigra of the midbrain. 2nd most common neurodegenerative disorder.

What are Lewy Bodies?

Aggregates of alpha-synucleic form round cytoplasmic inclusions called Lewy bodies.

What is the clinical presentation of Parkinson's disease?

Pill-rolling resting tremor

Akinesia

Flat affect

Freezing of gait/festinating

Loss of righting reflex

Incontinence, orthostatic hypotension

Dysphagia

What is the work-up for PD?

No specific lab indicator of disease exists.

What are the treatment options for PD?

Carbidopa-Levodopa

Dopamine agonists like pramipexole, ropinirole, bromocriptine, apomorphine hydrochloride

COMT inhibitors like entacapone

How do drugs for PD affect the symptoms and progression of disease?

They do not slow the progression of disease but they help the patient get used to the symptoms and help the body compensate for the changes.

What is brain deep stimulation?

A device used for PD that is inserted into the subthalamic nucleus and can provide great relief for patients.

What is Huntington's disease?

Disease of the basal ganglia (caudate nucleus, striatum and cortex). Irregular brief, flowing choreiform movements that often flit from one body part to another in an unpredictable manner.

Causes patients to have movement disorder, dementia symptoms and become very aggravated.

What is the inheritance pattern of HD?

Autosomal dominant

How does HD manifest?

Symptoms begin in 30s

Movement disorder

Psychiatric disturbance (aggressive behavior, psychosis)

Cognitive changes (subcortical so less memory problems associated)

How is HD diagnosed?

Genetic testing for repeats in HTT gene.

What is Syndenham's Chorea?

Associated with acute rheumatic fever

Rare at the present time, previously called St. Vitus dance

Usually recovers in 1-3 months

What is the treatment for Chorea?

No specific treatment

Caused by underactivity of GABA neurons and overactivity of dopaminergic neurons

Improvement with dopamine receptor blockers.

What are dystonia syndromes?

Torsional dystonia

Cervical dystonia

Blepharospasm

Cranial dystonia

Writer's Cramp

Dopa-resposive dystonia

What is Wilson's disease (Hepatolenticular disease)?

Genetic disease that prevents the body to eliminate excess copper, secondary to an abnormality in the ATB7 gene. Autosomal recessive. Copper accumulates in the liver and brain from a defective enzyme that links copper to transport protein ceruloplasmin.

What are the clinical manifestations of Wilson's disease?

Cirrhosis

Brain disease (lenticular: putamen, globus pallidus)

Hepato or splenomegaly

Jaundice

Fluid buildup in legs and abdomen

Easy bruising

Fatigue

How do you diagnose Wilson's disease?

Ceruloplasmin

Copper levels

Liver biopsy

What are the signs of Wilson's disease?

Dysphagia

Dysarthria

Ataxia

Tremor

Muscle stiffness

Behavioral changes

Patient will have liver toxicity s/sx first, then brain changes.

What ocular sign is seen in Wilson's disease?

Kayser-Fleischer ring.

What is Gilles de la Tourette syndrome?

Inherited disorder of the nervous system characterized by a variant expression of unwanted movements and noises

Coprolalia (uncontrolled swearing)

Affects males predominantly, cause uncertain.