Movement Disorders in the Rett clinic population

Rett Clinic Family Symposium

October 1, 2016

Anne Stratton, MD

Assistant professor, Dept Physical Medicine and Rehabilitation, University of Colorado

Children’s Hospital Colorado

Multidisciplinary Rett Clinic

Disclosures

• I have no relevant financial interests with any potential commercial entities related to this talk.

The challenges of movement…

• Megan never walked as a baby, but she did pull up in her bed. Shortly after she accomplished that, the regression started and she never walked. She also never crawled. She gets around on the floor by rolling and scooting on her back. She does love to be on her feet and I have assumed she is too old to learn to walk. But there is a spark inside me motivating me to continue trying to get her to walk. When she stands, she doesn’t seem to understand how to pick up her feet to take steps most of the time. Then at times she has actually taken more than one or two steps with support.

~ unknown Rett parent contributor

The Rett Syndrome Handbook, 2nd ed 2007, Kathy Hunter, editor.

Outline

1. Types of movement problems

2. Definitions

3. Natural history of movement disorder development in our clinic populations

4. Complications of movement disorders

5. Goals of treatment

6. Treatment options

7. Summary

Problems with movement in our population

• Stereotyped hand movements

• Apraxia

• Choreoathetosis

• Myoclonus

• Ataxia

• Parkinsonism

• Hypotonia

• Spasticity

• Dystonia

• Rigidity

Disorders of movement

• Stereotypic hand movements: wringing, mouthing, clenching, tapping. A motor programming and/ or signaling problem that strongly targets the hand/ upper extremity pathway regions of the brain.

• Motor apraxia: a programing problem. The signals for the desired/ intended actions or movements from the brain don’t get routed to the end muscles to complete the action correctly.

• Choreoathetosis: excessive signal issue. Involuntary jerky and writhing movements that child can’t control. Over activation of the wrong muscles at the wrong time.

Disorders of movement

• Myoclonus: aberrant signals. myoclonic “jerks.” Sudden spasms that cause limb or whole body movement

• Ataxia: a systems feedback problem. Problems interpreting or understanding where your body is in space and in relation to the ground when you make a movement.

• Parkinsonism: a “signaling” problem. Bradykinesia (slowed and diminished movements) and tremors due to poor signal transmission

Disorders of movement and muscle tone

• Hypotonia: Low muscle tone. Muscles are underactive at baseline. “Floppy”

• Spasticity: High muscle tone. Muscles are resistant to quick stretch and respond by firing abnormally “Stiff”

Disorders of movement and muscle tone

• Dystonia: High muscle tone. Antagonistic or opposite muscle pairs are active simultaneously, pulling body parts into abnormal twisted postures. “Stuck”

• Rigidity: High muscle tone. Muscles are so over active that they resist all movement in all directions and the body part seems “Frozen” or “Locked”

Further characterization of movement disorders

• Hyperkinetic: excessive movements• Dystonia

• Myoclonus

• Choreoathetosis

• Hypokinetic: decreased movements• Parkinsonism

• Bradykinesia

• Rigidity

Progression over a child’s lifespan

• Rett (MECP2), CDKL5, FOXG1, and all Rett like disorders overlap primarily because of the characteristic movement disorders

• Wide spectrum/ variation of severity

• Wide spectrum age of onset

• No set rules, only trends

Trends in movement disorder onset

• Hypotonia

• Hand stereotypies

• Spasticity/ dystonia

• Progressive dystonia

• Rigidity/ Parkinsonism

• Advanced parkinsonism

• Tendency to transition from hyperkinetic movements to hypokinetic movements with age

• FitzGerald P, Jankovic J, Percy A. Rett Syndrome and Associated Movement Disorders. Movement Disorders. 1990; Vol 5 (3): 195-202.

Complications of Movement disorders

• Function

• Discomfort

• Positioning

• Care/ hygiene

• Contracture development

Goals of treating movement disorders

1. Improve function

2. Improve comfort

3. Improve ease of care

Treatment options

• Non-pharmacologic• Therapy

• Stretching

• Bracing/ splinting

• Pharmacologic• Focal injections

• Systemic medications

• Other

Non-pharmacologic options• Stretching: lengthens the muscle

passively, temporarily reduces spasticity. Mainstay of home programs. Requires dedication.

• Therapy: functional movements provide natural stretch and reduces spasticity and dystonia. Focus on function and comfort.

• Bracing/ Splinting: positions a limb to provide prolonged stretch or inhibition of dystonic posturing

Pharmacologic options: Focal injections• Target the main problem muscles

• Shouldn’t have systemic side effects

• Temporary

• Botulinum toxin:

• Injected directly into muscle belly

• Blocks release of Ach (acetylcholine) from the nerve, thus diminishing the signal for the muscle to fire

• Nerve regenerates ability to release Ach in ~3-4 months

Pharmacologic options: Focal injections

• Phenol blocks

• Injection directly at the motor nerve

• “Melts” the nerve endings so they can’t communicate as well with the muscle

• Done under sedation

• Only certain muscles (biceps, hamstrings, and hip adductors) due to nerve anatomy

• Also temporary since the nerve endings regenerate (3-6 months)

Pharmacologic interventions: Systemic medications

• Baclofen

• Trihexyphenadyl (Artane)

• Diazepam (Valium)

• Clonazepam

• Carbidopa/ levodopa (Sinemet)

Systemic Medications: Baclofen

• Treats spasticity and dystonia

• Mimics neurotransmitter in spinal cord that sends “relax” signals (GABA)

• Can be sedating- especially at higher doses

Systemic Medications: Trihexaphenadyl

• Parkinson drug

• Treats dystonia and rigidity

• Anticholinergic (blocks acetylcholine action)

• Can cause dry mouth (may be helpful in drooling)

• Can be sedating

Systemic Medications: Diazepam and Clonazepam

• Benzodiazepines

• Treats spasticity, dystonia and rigidity

• Enhance the effect of the “relax” signal neurotransmitter GABA (at it’s A type receptor)

• Can be very sedating

Systemic medications: Carbidopa/ Levodopa

• Parkinson drug

• Treats bradykinesia, rigidity

• Mimics neurotransmitter dopamine in the brain

• Combination of 2 medications: • Carbidopa

• Levodopa

• Levodopa • active med in the brain

• Has intolerable GI side effects by itself

• Carbidopa• helps regulate the metabolism of levodopa

• protects against nausea and vomiting side effects

Other options

• Baclofen pump• Surgically implanted under thin

layer of muscle in abdomen

• Catheter tubing tunneled under skin from pump to spine

• Tubing inserted into CSF space around spinal cord

• Sterile liquid baclofen dripped into CSF at spinal cord

• Refilled in office at least every 6 months

?

Treatment options

• Frequently a combination of therapy is required

• Each child is unique and responds differently to each intervention

• Treatments may change over time

• Re-evaluate goals for treatment over time

• Work with your team to be creative

Summary

• Rett syndrome and Rett like disorders have similar problems with movement

• Hyperkinetic and hypokinetic movement disorders

• Problems with movement

• Problems with muscle tone

• Pharmacologic treatment options

• Non-pharmacologic treatments

• Combine therapies as child needs

• Get creative with your team based on your goals

References and resources• Chapleau C, Lane J, Larimore J, et al. Recent progress in Rett syndrome and

MeCP2 dysfunction: assessment of potential treatment options. Future Neurol. 2013; 8(1):1-9.

• Fitzgerald OM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord. 1990; 5 (3):195-202

• Hymphreys P, Barrowman N. The incidence and evolution of parkinsonianrigidity in Rett syndrome: a pilot study. Can J Neurol Sci. 2016; 00:1-7.

• Larsson G, Engerstrom I. Gross motor ability in Rett syndrome- the power of expectation, motivation and planning. Brain and Devel. 2001; 23: S77-S81.

• Nomura Y. Neurophysiology of Rett syndrome. Brain and Devel. 2001; 23: S50-S57.

• Percy A. Rett syndrome: recent research progress. J of Child Neurol. 2008; 23 (5): 543-549.

• Rocky Mountain Rett Association website: http://rmrett.org/• The Rett Syndrome Handbook, 2nd ed 2007, Kathy Hunter, editor

Thank you!

Rocky Mountain Rett Association: http://rmrett.org/