L2 Movement Disorders

Question 1

what is the mechanism of action of tetrabenazine? (HD)

Answer 1

o Bind to and block vesicular monoamine transporters (VMATs) preventing the transporter from allowing dopamine particles into the vesicle (action potential goes down neuron and when vesicles go to fuse on the presynaptic side they don’t release as much = reduce dopamine)
o Bind and affect how the dopamine receptors are going to respond to dopamine = reduce signalling of post synaptic side

Question 2

what is the function of haloperidol? (HD)

Answer 2

Antagonists to dopamine receptors

improves motor function and psychosis associated with HD

Question 3

what are the physical side effects of tetrabenazine and haloperidol? and why is this bad? (HD)

Answer 3

Physical side of effects of these drugs (drowsiness and less ability to move) can be worse than chorea. As the disease progresses, natural dopamine levels fall, leading to loss of chorea and increase in rigidity and slowness

Question 4

what is multiple sclerosis?

Answer 4

MS is an autoimmune disease in which the immune system attacks and degrades the myelin sheaths which usually insulate and protect nerves of the brain, spinal cords, and optic nerves, resulting in ‘short circuiting’ with each other (voluntary movement might be blocked because it isn’t reaching brain signalling)

Question 5

how is multiple sclerosis acquired?

Answer 5

• Unknown- there are some very interesting links between MS patients, genetics and environmental factors
• Gender- women are 2% more likely to have MS than men; but then women generally suffer from more autoimmune diseases than men
• Race- Caucasians are more than twice as likely to develop MS compared to other racial groups

Question 6

is multiple sclerosis genetically transmitted?

Answer 6

• In normal population, risk is 0.1%
• If an immediate family member has MS, your risk factor increases to 3%
• If a distant member has MS, your risk is 1%. However, if both parents were to have MS, you are at 20%.
• Identical twins with MS: 30%.

Question 7

what are the correlations between socio-economic status and infection to the acquiring of multiple sclerosis?

Answer 7

• Socio-economic status: the more urban and better educated you are, the more at risk you are (environmental factors? Detection?)
• Infection: MS may be a delayed effect of having a viral infection in early childhood, such as shingles, chicken pox, measles and certain herpes. The older you are with these infections, the greater your risk of MS

Question 8

what are the environmental factors that influence acquiring multiple sclerosis?

Answer 8

• Latitude on planet earth: if you are born above or below 40 degrees latitude, your risk factor increases. The further away you are from the equator, the greater your risk factor
• Migration: people migrating from an area where MS is common to an area where it is less common experience a decrease in disease rates to a level intermediate to the places of origin and destination, whereas people who migrate from areas of low risks to areas of higher risk tend to retain the lower risk of their area of origin. Data on age at migration suggest the risk of disease is established largely in the first two decades of life, although a strict cut-off point (e.g. age 15) cannot be established
• Environmental factors such as UV or vitamin D levels are instrumental for these latitude effects

Question 9

what is the theory regarding multiple sclerosis and human herpes virus?

Answer 9

A study of 16,000 people suggests that human herpes virus 6A (HHV6A) is a risk factor for MS
Theory: HHV6A infects oligodendrocytes, the cells which generate the protective myelin sheath around neurons. Virus may borrow some myelin proteins. Immune cells then catch the virus and express the proteins on their surfaces to other immune cells- and thus the immune cells may target the oligodendrocytes in error

Question 10

what are the symptoms of multiple sclerosis?

Answer 10

numbness, tingling, cognitive dysfunction, depression, dizziness, vision problems, fatigue, muscle spasms, weakness, walking difficulty, bowel dysfunction, pain

Question 11

what are the four main multiple sclerosis disease courses

Answer 11

• clinically isolated syndrome (CIS)
• relapsing-remitting MS (RRMS)
• secondary progressive MS (SPMS)
• primary progressive MS (PPMS)

Question 12

describe what the multiple sclerosis disease course called clinically isolated syndrome:

• is
• what the presentation of lesions can result in
• treatment

Answer 12

• First episode with symptoms caused by inflammation and demyelination in the CNS- must last 24 hours. Some people experience this and never progress to MS, but all MS patients will have this starting point
• If CIS diagnosis and have lesions seen on brain magnetic resonance image (MRI), there is a high likelihood of a second episode in the future and a MS diagnosis
• If no lesions are present, then MS likelihood is much lower
• Treatment would include “disease modifying therapy” and this may delay the onset of MS, which is very advantageous

Question 13

define the multiple sclerosis disease course: relapsing-remitting MS

Answer 13

• Most common disease course
• Has defined ‘attacks’ of new or increasing neurologic symptoms (relapses)
• These relapses then have period of time with partial or complete recovery (remissions)
• During remissions, all symptoms may disappear or some may continue and become permanent
• RRMS can also have ‘active (with relapsed or new MRI activity) or not active’, ‘worsening (an increase in disability following a relapse) or not worsening’
• 85% of MS patients will have this diagnosis

Question 14

define the multiple sclerosis disease course: secondary progressive MS

Answer 14

• SPMS starts as RRMS, but the patient transitions into secondary progressive phase, in which there is progressive worsening of function
• This can be characterized as either ‘active (re relapses and/or new MRI activity) or not active’, as well as ‘with progression (disability accumulation over time without relapses or new MRI activity) or without progression)

Question 15

define the multiple sclerosis disease course: primary progressive MS

Answer 15

• PPMS has worsening accumulation of disability from the onset of symptoms, without relapses or remissions. It can also be ‘active or not active’, ‘with progression or without progressive’
• Approximately 15% of patients with MS are diagnosed as PPMS
• Each person’s experience will be unique. PPMS can have brief periods when the disease is stable, as well as times when there is increasing disability without relapses of lesions in MRI

Question 16

what are the ways medications are used to treat and manage multiple sclerosis?

Answer 16

Medications are used in three ways:

a. To modify the disease course
b. To manage release
c. To manage symptoms

Question 17

how are the drugs interferon beta 1a or 1b and glatiramer acetate used to modify the disease course of multiple sclerosis?

Answer 17

Interferon beta 1a or 1b:
• proteins which are copies of human interferon protein (1a) or similar in structure (1b)
• These supress the immune system. It is injected into muscle of a weekly regiment and is useful in patients with progressive MS
• Their use to reduce risk of disability progression with fewer relapses and reduction in number and size of active lesions in the brain on MIS
Glatiramer acetate:
• a small fragment of protein that resembles myelin protein. This decreases relapse frequency and must be injected once per day. This may serve as a ‘decoy’ for the immune system (gives immune system a false target).
• Each of these drugs reduces relapse frequency to about 33% with minimal side effects. They can stabilise the disease but are costly

Question 18

explain why multiple sclerosis relapses occur and what drug can manage these relapses

Answer 18

MS Relapses are largely caused by inflammation in the CNS that damages the myelin coating around nerve fibres. This damage slows or disrupts transmission of nerve impulses and causes the symptoms of MS. Most will gradually resolve without treatment. If relapses are severe (loss of vision, severe weakness or poor balance), which interferes with mobility, safety and ability to function, there may be use of oral or IV corticosteroids. These do not have a long-term benefit on the disease.

Prednisone/methylprednisolone: these are anti-inflammatory drugs and may be used for 5-10 days either at home or in the hospital. Same medications as used for asthma- another inflammatory illness.

Question 19

what are some drugs/areas of interest when managing symptoms of multiple sclerosis?

Answer 19

• Spasticity: baclofen (GABAb agonist)- works on receptor in spinal column and relieves spacisity, diazepam (benzodiazepine)- relaxation
• Pain: codeine, aspirin, morphine
• Optic neuritis: oral corticosteroids
• Management of impaired bladder and bowel function
• Splinting for muscle contractures
• Counselling etc.
• Physical support
• Psychological support

Question 20

what is motor neuron disease?

Answer 20

A group of diseases in which the motor neurones undergo degeneration and die

Question 21

what are the subtypes of motor neuron disease?

Answer 21

amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP), primary lateral sclerosis (PLS)

Question 22

what are symptoms of motor neuron disease

Answer 22

muscle wasting, weakness and respiratory failure leading to death within 2-5 years

Question 23

In motor neuron disease, what is happening to the neurons and where?

Answer 23

When there are disruptions in the signals between the:
Lower motor neurons and the muscle: the muscles do not work properly; the muscles gradually weaken and may begin wasting away and develop uncontrollable twitching
Upper motor neurons and the lower motor neurons, the limb muscles develop stiffness (called spasticity), movements become slow and effortful, and tendon reflexes such as knee and ankle jerks become overactive.
Over time, the ability to control voluntary movement can be lost.

Question 24

what are the types of muscle atrophy and wasting

Answer 24

a) disuse atrophy, which can be reversed with activity and nutrition,
and b) neurogenic atrophy, in which there is damage to the nerve innervating the muscle, not readily reversed

Question 25

what is oxidative stress?

Answer 25

Oxidative Stress: persistent imbalance in which oxidants > antioxidants. Oxidative stress is a cause and consequence of inflammation and contributes to neuronal cell loss.

Question 26

what is the current drug treatment of motor neuron disease

Answer 26

* Riluzole is believed to protect motor neurons from excitotoxicity, may prolong motor neuron survival * Riluzole may block voltage-gated Na+ channels, reducing glutamate release from motor neurons. Glutamate is excitatory and reducing this may be neuroprotective. * Riluzole postpones the time that a patient may need a tracheotomy by up to three months

Question 27

what drugs can be used to treat symptoms of motor neuron disease

Answer 27

* As with multiple sclerosis, spasticity can be partly controlled with baclofen, a GABAb agonists * When activated by the patient, baclofen is injected into the spinal cord where it can bind to GABAb receptors and inhibit spasticity

Question 28

why is respiratory care important of motor neuron disease important?

Answer 28

* Maintaining good respiratory function is crucial for patients and not just in the end stages of disease * Using mask ventilator systems during the night, which are small and portable, has been shown to improve the QOL as well as to lengthen survival times

Question 29

what is muscular dystrophy

Answer 29

Muscular dystrophy is a group of disorders which involve progressive loss of muscle mass and thus loss of strength

Question 30

what is the most common form of muscular dystrophy

Answer 30

* Most common form- Duchenne muscular dystrophy- impacts young boys but other variants can have effects in adulthood * It is caused by genetic mutations which interfere with the production of muscle proteins required to build and maintain muscle tissue

Question 31

what are the muscular dystrophy symptoms

Answer 31

* Pain and stiffness in the muscles * Difficulty with running and jumping, standing up or sitting up * ‘walking on toes’ * Waddling gait, frequent falls * Learning disabilities, as well as delayed speech * As this disease progressed, patients lose the ability to walk, as well as experiencing a shortening of muscles and tendons * Breathing may require assistance. Heart muscle may be weakened, leading to cardiac issues, and difficulties swallowing may occur, leading to aspiration pneumonia and possible feeding tube use

Question 32

how is muscular dystrophy diagnosed?

Answer 32

* Enzyme assay for creatine kinase (CK) which is produced by damage muscles. Elevation in these levels can suggest muscular dystrophy * Genetic testing * Heart monitoring: ECG * EMG * Biopsy

Question 33

what are the two most commonly prescribed drugs for muscle dystrophy?

Answer 33

o Corticosteroids: although this type of medication can help increase muscle strength and slow progression, their long-term use can weaken bone and increase weight gain o Heart medications: if the muscular dystrophy impacts the heart, beta blockers may be useful

Question 34

what is cerebral palsy?

Answer 34

Cerebral palsy is a physical disability that affects movement and posture. It is the most common physical disability in childhood

Question 35

what are the motor types and parts of the body classifications of cerebral palsy?

Answer 35

Motor types: • Spastic: 70 – 80% Characterised by damage to the motor cortex of the brain before, during or after birth. Results in increased muscle tone (hypertonicity) and stiff tight movements • Ataxic: 6%. Damage to the cerebellum (balance centre of the brain.) Results in clumsiness, instability, and imprecision in movements. • Dyskinetic: 6% Damage to the Basal Ganglia. Results in involuntary movements e.g. dystonia (twisting repetitive movement); chorea (quick dance-like movement of the hands and feet); and/or athetosis (involuntary writhing movements) • Combination Parts of the body: • Hemiplegia: UL and LL on same side • Diplegia: LL both or UL both • Quadriplegia: all limbs

Question 36

what is cerebral palsy caused by?

Answer 36

* Cerebral palsy is caused by brain injury or brain malformation that occurs before, during or immediately after birth while the infants brain is under development * But how a brain injury affects a child’s motor functioning and intellectual abilities is highly dependent on the nature of a brain injury, where the damage occurs and how severe it is

Question 37

what are babies and toddlers symptoms for cerebral palsy?

Answer 37

Babies: • Low muscle tone (baby feels ‘floppy’ when picked up) • Unable to hold up his/her own head while lying on their stomach or in a supported sitting position • Muscle spasms or feeling stiff • Poor muscle control, reflexes and posture • Delayed development (can’t sit up or independently roll over by 6 months) • Feeding or swallowing difficulties • Prefers to use one side of their body Toddlers/children: • Although the brain of toddlers/children w/cerebral palsy remains injured, the injury does not get worse as they develop • Depending on the level of severity of cerebral palsy, toddlers and children may experience difficulties with physical development such as: not walking by 12-18 months, not speaking simple sentences by 24 months

Question 38

how is cerebral palsy diagnosed?

Answer 38

* Special attention to the child’s movements- both their voluntary movements as well as their muscle tone * Some children may have very relaxed, floppy muscles, while others have stiff, tight muscles * Doctors will also look for any unusual postures or if the child favours one side over the other * One of the frustrations for parents is that sometimes a diagnosis can take a long time w/ repeated tests and visits to specialists * This may be because the child has a mild form of cerebral palsy, but it could also be because the doctor needs to make sure it is not another type of movement disorder that may be progressive (get worse over time)

Question 39

what drug treatment options are there for cerebral palsy?

Answer 39

• Medications that assist with movement issues, such as in MND and MS, can be used. These include diazepam and baclofen, which can be delivered using a pump implant -- Baclofen: loosens spastic muscles throughout the body • Many children with cerebral palsy benefit from botulinum toxin type A injections into muscles affected by spasticity. This prevents their contraction -- botulinum toxin type A: induces muscle paralysis in isolated muscle groups