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

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Placebo Control: What is it? Why do we use it? Is it ethical?

Placebo Control: What is it? Why do we use it? Is it ethical?
By:Tom Talbot, MD MPH
Vanderbilt School of Medicine

Placebo
* Placebo = “I shall please”
* Pharmocologically inert substances used to satisfy patients that something being done for them (“please the patient”)
* “Any therapeutic procedure (or that component of any therapeutic procedure) which is given deliberately to have an effect, or unknowingly has an effect on a patient, symptom, syndrome, or disease, but which is objectively without specific activity for the condition being treated. The therapeutic procedure may be given with or without the conscious knowledge that the procedure is a placebo, may be an active (non-inert) or inactive (inert) procedure, and includes, therefore, all medical procedures no matter how specific – oral and parenteral medications, topical preparations, inhalants, and mechanical, surgical, and psycho-therapeutic procedures. The placebo must be differentiated from the placebo effect which may or may not occur and which may be favorable or unfavorable. The placebo effect is defined as the changes produced by placebos. The placebo is also used to describe an adequate control in research.” -- Shapiro

Placebo: Why Use it?
* Need to control for therapeutic aspects of prescribing a medication or procedure not directly due to the medication or procedure itself
* i.e. . . . The Placebo Effect

Placebo: History
* First placebo-controlled trial:
o Sanocrysin vs. distilled water to treat TB
o 1931
The Story of Kebrozion
* Pt. with lymphosarcoma
* Patient given Kebrozion
* “The tumor masses had melted like snowballs on a hot stove, and in only a few days, they were half their original size!”
* 2 months later – Kebrozion outed
* Pt given a “new form” of Kebrozion
* Water injections
* Tumors resolved remission
* 2 months later: AMA – “This stuff’s worthless”
* Pt. returns in extremis and dies

Kebrozion, Pt 2
Issues
* Does use of placebo remove access to effective standard of care?
* Is a trial that does not use placebo arm scientifically rigorous?
* Does use of a placebo sacrifice ethics and an individual patient’s welfare?

Placebo-Control: PROS
* Need placebo control to insure validity
Placebo-Control: PROS
* Need placebo control to insure validity
* Argue that no drug should be approved for patient use if it is not clearly superior to placebo or no treatment
* Scientifically invalid research is itself unethical
* Harm and discomfort nonexistent or small in some cases

Placebo-Control: PROS
* Places patients at less risk of harm due to need for smaller numbers for placebo-controlled trials
o Greater power with smaller numbers than noninferiority trial
o Many more exposed to drug in non- placebo trial
* FDA:
o Placebo controls required for disorders of moderate severity and pain
o Beta-blocker not approved for angina (even though it was shown to be as efficacious as proven tx) due to lack of placebo comparison
* Unethical to withhold effective treatment
* Places demands of science ahead of right and well-being of patients
* Your study question has to change:
o Is the new drug better than proven effective therapy?

Placebo-Control: CONS
* Patients are owed medical care for ailments when they present to healthcare providers
* Not truly testing therapy against “no treatment” placebo effect
Rothman KJ et al NEJM 1994;331:394 Enserink M Science 2000;490:418-9
* Declaration of Helsinki:
o “Every patient -- including those of a control group, if any -- should be assured of the best proven diagnostic and therapeutic method.”
o 2000 Revision: Placebos may be used only when there are no other therapies available for comparison with a test procedure
* “Concedes to individual investigators and to IRBs the right to determine how much discomfort or temporary disability patients should endure for the purpose of research”
Clinician/Physician Clinical Researcher
Ethical?
* Subjects: Cancer patients
* Intervention: Odansetron vs. placebo
* Indication: Post-chemotherapy emesis and nausea
* ? Proven effective therapy for nausea
* Subjects: Men with hair loss
* Intervention: Compound X vs. placebo
* Indication: Prevent hair loss
* ? Lack of sequelae from placebo use
* Subjects: Pts. with depression
* Intervention: Compound X vs. placebo
* Indication: Reduction in depressive sx.
* ? Places placebo pts. at risk for severe sequelae of depression

Ethical Balance
* Valid research vs. Undue harm
Validity Minimize Risk
Ethical Balance Validity
Minimize Risk
* Valid research vs. Undue harm
Placebo-Control and Procedures/Surgery
“A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee”
* Randomized, PLACEBO-controlled trial
* Endpoint: Pain in study knee
* Placebo:
o Did not receive general anesthesia
o Knee prepped, draped
o Three 1cm incisions made
o Knee manipulated as if arthroscopy performed
o No instruments entered the incisions
Placebo-Control and Procedures/Surgery
* Informed Consent:
o Explained study thoroughly
o Subjects had to write the following:
+ “On entering this study, I realize that I may receive only placebo surgery. I further realize that this means that I will not have surgery on my knee joint. This placebo surgery will not benefit my knee arthritis.”
o 44% declined
So . . . What do you think? Is this ethical?
Placebo-Control and Procedures/Surgery
* Placebo is not necessarily without risk
* Placebo surgery “violates an essential standard for research: the requirement to minimize the risk of harm to subjects.”
* Again – is there harm in performing an unvalidated procedure?
* Does the risk exceed that of other research procedures from which the subject does not receive benefit?
o Bronchoscopy in healthy adults
o Placement of P-A catheter in non-critically- ill subjects
o Muscle biopsy in healthy adults
* Must be informed
* Must be told that misleading tactics may be used
* Must not be misled about the chances of receiving the sham procedure
* Must be debriefed after study complete and unblinded
* Arthroscopy Study Results:
o No difference in pain scores
o The surgery itself had been causing undue risk (and cost – $3.25 billion/year)
o Without the placebo-controlled study, this would never had been discovered

Cultural Issues and Placebo-Control
* What about when conducting research in other countries?
* “Standard of care” is different due to:
o Access to meds
o Access to healthcare
o Basic infrastructure issues
o Cultural beliefs
* Prevention of fetal-maternal transmission of HIV
* Population: African women
* Intervention: Short course AZT vs. placebo
* Problem: AZT shown effective (longer course)
* Critics: Withheld effective, morbidity-reducing treatment
* Supporters: “Standard of care” in the country was no meds – no money or availability

Cultural Issues and Placebo-Control – Ethical?
* Generally felt that the cultural “standard of care” for studies in developing countries should be that of the investigator’s host country

THE USE OF PLACEBO
Placebo Acceptable If . . .
* Use of placebo does not impair health or cause “severe” discomfort
* Existing therapies only partly effective or have very serious side effects
* Low frequency of condition – would prevent enrollment for a larger trial
* Participants at risk of harm from nonresponse are excluded
* Placebo period is a limited to minimum required
* Careful monitoring is insured
* Explicit withdrawal criteria for AE
* Informed consent explicit as to why placebo should be used
* Improved survival or prevention of irreversible morbidity does not exist for any therapy
Questions

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MRI Safety and Policies & Procedures

MRI Safety and Policies & Procedures

Magnet Safety at ALL TIMES
Outline
Understanding Magnets
o Your role in MR Safety
o Metallic Screening
o Screening Patients / Colleagues
o Other Safety Considerations

What to do in Emergencies
MRI Department Policies and Procedures
Preview MRI Safety Videotape

Magnetism / Magnets
* All substances possess some form of magnetism.
* The degree of magnetism exhibited depends on the atoms that make-up the substance.
* Magnetic susceptibility is the ability of a substance to become magnetized.
* Ferromagnetic substances, such as iron have a large magnetic susceptibility, it is easily magnetized permanently and becomes a magnet itself.
* All magnets have a North and a South pole.
* All magnets have a “fringe” magnetic field which exists in the vicinity surrounding the magnet.

Magnetic Fringe Fields
* The fringe magnetic field is the magnetic field which exists in the vicinity surrounding the magnet.
* This field may extend many meters from the magnet itself.
* These imaginary lines of force demonstrate the pattern of the magnetic field.
* Safety and operational concerns make it necessary to contain the fringe field to a small area.
* Magnetic fields are measured in units of Gauss or Tesla.

MRI Safety at ALL TIMES
A STATIC MAGNETIC FIELD IS ALWAYS PRESENT 24hrs/day, 365 days/yr. EVEN WHEN NOT IN USE.
ANY PERSON USING THE MAGNET MUST BE CERTIFIED AFTER ATTENDING THE MRI SAFETY TRAINING CLASS.
ONE MUST BE TRAINED ON THE SCANNER INTERFACE BEFORE SCANNING.

What is your role in MR Safety?
The greatest risk of injury and damage to the system results from:
o Misuse or abuse of the MR equipment
o Failure to comply with recommended safety procedures
o Lack of proper inspection and maintenance of the MR equipment

Who should know MR Safety?
All in-house personnel that have reason to enter the MR suite area should be trained in MR safety procedures:
o MR technologists, students, researchers, transporters and other medical personnel
o Maintenance and janitorial personnel
All personnel must be thoroughly briefed about the potential risks involved and reminded not to bring any ferromagnetic items into the magnetic field.

Examples of items in-house personnel may have that can become projectiles if brought into the magnetic field

Tool Kits
Clipboards, Metal Pens
Tools
Gurneys, Wheelchairs
Vacuum Cleaners
Oxygen Cylinders
Buffers
Stethoscopes
Buckets
Scalpels, Syringes, Needles
Dustpans
Scissors, Hemostats
Maintenance & Janitorial personnel
MR technologists, students, researchers, transporters & other medical personnel

Who should know MR Safety?
Public safety forces that may respond to the MR suite for an emergency must also know the potential hazards of the MR equipment.
o Law enforcement personnel
o Fire department personnel

A person from the MR site should discuss the possible hazards with these people and provide them with handouts that will reinforce the information.

Examples of items public safety forces may have that can become projectiles if brought into the magnetic field
Breathing apparatus
Fire Extinguishers
Flashlights
Pike poles
Clipboards
Nozzles
Handcuffs
Hose couplings
Knives
Axes
Guns
Fire Department personnel
Law enforcement personnel

MRI Safety - Projectiles
* Projectile effects of metal objects seriously compromise safety. The potential harm cannot be over emphasized.
* Many types of clinical equipment are ferromagnetic and should never be brought into the scan room.
* Items may be tested for magnetic susceptibility with a hand-held magnet located at each MR station.

Metal Objects Becoming Projectiles
Fatal Accidents CAN Happen!
Patient Emergencies
Should a condition exist where the patient is having a medical emergency, all efforts must be made to quickly and safely remove the patient from the scan room.
Once the patient is removed from the MR scan room, close the door to prevent re-entry.
Under no circumstances should a “code team” be allowed to enter the scan room without proper screening!
Controlled Access Area
Although not detectable by the human senses, a magnetic field can be dangerous to equipment and to people.
Since a magnet is always “at field,” safety procedures must be followed to prevent accidents.
For the safety of patients and personnel, controlled access areas are established.

Controlled Access Area
* These areas are established for the safety of patients and personnel.
* The area is labeled with the use of warning signs and markings to prevent the entry of ferromagnetic objects into the controlled access area and to limit the access of individuals with medical implants near high magnetic fields.
* Public access begins at the 5 gauss line (0.5mT).

Equipment / Personal Items
The magnetic field can seriously damage or impair the operation of equipment or personal items such as:
o Oscilloscopes (slow moving electron beams)
o Camera
o Watches
o Credit / Bank cards
o Hearing Aids
o Hair Accessories, Belt Buckles, Shoes

Screening Procedures
* At least one MR operator must screen the patient for possible contraindications that could affect the MR scan. See Patient History and Safety Screening form.
* Check implanted devices in the Reference Manual for Magnetic Resonance Safety by Frank Shellock, Ph.D. or by using MRIsafety.com
Example of MRI Metal Screening Sheet
Screening Procedures
Static magnetic fields can alter the operation of electrically and mechanically operated implants and must remain outside the 5 gauss line.
Pregnant medical personnel should take precautions and remain outside of the magnet room during scanning.
Questions about implants not found in reference material should be discussed with a licensed, MRI technologist or a radiologist before allowing the patient to be scanned.
Absolute Contraindications
* Cardiac Pacemakers (except in rare, controlled environments)
* Cochlear (inner ear) implants
* Swan-Ganz catheters with thermodilution tips
* Ferromagnetic or unidentifiable aneurysm clips of the brain
* Implanted neuro stimulators
* Metal or unidentifiable foreign bodies in the eyes
* Shrapnel near a vital organ
Bioeffects
There is no conclusive evidence for irreversible or harmful bioeffects in humans below 3.0T.
Reversible abnormalities may include but are not limited to:
o Localized tissue and core body temperature heating
o Cutaneous sensations (tingling)
o Peripheral nerve stimulation (involuntary muscle contractions)
o Burn hazards
* Burn Hazards are caused by damaged hardware or by electrical currents produced in conductive loops of material.
* Localized heating is caused by RF irradiation energy absorption to a volume of tissue.
* Dissipation of the absorbed RF energy is described in terms of Specific Absorption Rate (SAR), measured in watts/kg.
* SAR is calculated by the patient’s weight and the expected increase in body temperature for each imaging pulse sequence.
* Patients with poor thermo-regulatory systems must be carefully monitored.
Acoustic Noise
The MR scanner can produce very high acoustic noise levels.
Some patients may experience discomfort from the associated noise of the scanner.
Prior to scanning, it is strongly recommended that earplugs be provided to the patient to reduce the noise level by at least 25dB.

Operating Safely
When operating the MR equipment, be attentive to the following abnormal conditions:
* Louder-than-normal motor noises
* Sparks
* Components overheating
* Smoke or odors coming from the electronic equipment or from within the scan room.
Do not operate equipment with protective panels opened or removed, there is risk of electric shock and can cause image artifacts.

Magnetic Field / Scan Room Emergencies
If an emergency situation arises, you may need to quickly bring down the patient systems and remove power from the MR system.
The nature of the emergency will dictate which procedure you follow. Each procedure has a distinct and specific purpose.
Each magnet is equipped with two emergency buttons:
* Emergency Stop / Shut Off
o Turns off all incoming electrical power to the magnet Power Distribution Unit (PDU)
* Quench or Emergency Run Down
o Causes immediate collapse of the superconductive magnetic field within minutes

FAMILIARIZE YOURSELF WITH THESE BUTTONS. KNOW THE DIFFERENCE!
Emergency Stop / Shut Off Button
Shutting power to the PDU may be required for life threatening situations such as:
* Fire in the computer room
* Fire, sparks, loud noises emanating from the scan room
* Flooding or sprinkling system goes off
* Catastrophic equipment failure
***Keep in mind that when this button is pushed, it does not initiate a quench, the magnet remains “at field.” Exercise caution, make sure that all ferromagnetic materials remain outside of the scan room***
Quench / Emergency Run Down Button
The following situation is THE ONLY TIME that may require quenching of the magnet:
* Large magnetic object pins or impales a person against the magnet and no other method can prevent further injury or free the person.
Do not attempt to pull large magnetic objects (oxygen tanks) from a magnet field. The object may change its magnetic polarity and re-align itself on the magnet and become a projectile, causing a serious or fatal injury.
Do not touch a quenched magnet. Under certain conditions, an electrical potential of >1,000 volts could exist on the surface of the magnet.

Quenching
Definition: a loss of superconductivity of the magnet coil due to a local temperature increase in the magnet as it becomes resistive, resulting in rapid evaporation of liquid helium in the cryostat and quickly reducing the magnetic field strength.
* A quench may happen spontaneously or can be manually instigated in case of an emergency.
* Quenching may cause severe and irreparable damage to the superconducting coils (magnet).
* A magnet quench will result in several days’ downtime, so do not press the button except in a true emergency.
* Do not attempt to test this button!

Emergency Buttons @ MR1 Univ. of Utah Hospital
* QUENCH BUTTON
o Button is located on the east wall (with window).
* E-STOP BUTTON
o Button is located behind the door as you enter the scan room (on the right).
QUENCH
OXYGEN
SENSOR
QUENCH
University of Utah Hospital and Clinics
MRI Department Policies and Procedures
This manual is available at all sites having a MRI scanner. Detail of all departmental situations can be reviewed. The following safety considerations are further highlighted:

Cryogen Safety Oxygen Monitors
Metallic Screening Pregnancy / Nursing
Magnet Quench Medical Emergencies
Magnetic Field / Scan Room Emergencies
Summary
* MRI scanners are powerful magnets with the ability to attract ferromagnetic objects.
* Any personnel around the MRI suite must be adequately screened for metallic implants and personal items before entering the scan room.
* Patients in the scanner must be carefully monitored for reversible bioeffects caused by the magnet’s hardware.
* Become familiarized with E-Stop vs. Quench buttons at each scanner.
* Review Policies and Procedures Manual

Congratulations!
You have completed the University of Utah Hospital and Clinics MRI Safety Training course!
Please review a safety video that demonstrates the powerful forces of MRI magnets.
Following written certification, you will be authorized to aid or assist an MRI technologist with patient examination procedures.

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