Treatment of Children with - PowerPoint Presentation

1. Treatment of Children with Rett Syndrome from the physiatry PerspectiveLaura L. Deon, MDRush University Medical CenterLa Rabida Children’s Hospital

2. IntroductionRett syndrome is a unique developmental disorder caused by a MECP2 mutation that usually occurs in infant girls.It is characterized by normal development up until between 6 and 18 months of age and then regression of developmental milestones occurs. The management of children with Rett syndrome ideally involves a team of professionalsPhysical therapistsOccupational therapistsSpeech therapistsPhysiatristsPediatric neurologistsOrthotistsPrimary CareGIPediatric orthopedist

3. The Physiatrist’s RoleCare and comfortEase of care givingProper equipment makes care giving easierHoyer lifts, wheelchair lifts/ramps, bath chairs, adapted vansAdaptive equipment for improved functionProper DME for home use to improve comfort and safetyHospital bedsSpecialized chairs for feeding/bathingManagement of SpasticityTherapy, bracing, oral medications, and intramuscular medications

4. SplintingMay help improve function in some cases by temporarily decreasing stereotypic movements.Help promote neutral positioning of the hands, limbs, and feet.Should be used based on tolerance and comfort of the patient.

5. Wrist and Hand splintsCan control thumb and wrist muscles that may be affected by increased tone.An open hand and thumb may lead to increased function through improved grasp.A neutral wrist may promote better hand function.

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7. Upper extremity SplintsMay provide support to the arm to improve functional activities such as eating.May do a modest job of preventing hand wringing or hand mouthing.Can be used for brief periods during activities where decreased wringing or hand mouthing may improve function such as computer usage.Should not be used for extended periods since inhibiting hand wringing/mouthing over prolonged periods can cause agitation or increased intensity of the stereotypic movements.

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9. Communication devicesCan assist with communicating basic needs and more complex ideas.Communication cards/boards can be used as well as more advanced machinery such as an ipad to tobi/dynavox.Can be controlled with eye gaze or a switch mechanism.

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11. Equipment for ADLs

12. Seating SYstems

13. Specialized Bedding

14. Comfort Items

15. Definition of SpasticitySpasticity is a common consequence of abnormal brain development.Spasticity is a velocity-dependent resistance of a muscle to stretch. It is defined as having one or both of the following signs: 1) resistance to externally imposed movement increases with increasing speed of stretch and varies with the direction of joint movement2) resistance to externally imposed movement rises rapidly above a threshold speed or joint angle

16. Spasticity can vary depending on several factors such as the patient’s level of activity, level of alertness, emotional state, and discomfort. On exam, upper motor neuron signs such as hyperreflexia, clonus, and Babinski response are commonly present.

17. Spasticity managementThere are many ways to treat spasticity. Carefully defining the goal of treatment is as important as the treatment itself. The goals should be explored and discussed in the context of the child’s function with the family and the medical team. Management of spasticity or hypertonia is divided into global or whole body involvement and focal problems, which may affect one joint level of one extremity.

18. Choosing a conservative therapy such as bracing or medications to manage spasticity should maximize function or improve the child’s general care and comfort and minimize side effects or complications. The treatment should also suit the patient, the family, and the available community resources and capabilities.Be sure to keep the goal in mind….ComfortPreventing orthopedic complicationsBrace wear/shoe wear

19. Physical Treatment MethodsHypertonia and decreased selective motor control contribute to decreased frequency and variety of voluntary movementsWith the decreased frequency and variety of movements, patients are at risk for contractures which can be treated and often times prevented with proper care.

20. What is a contracture?A joint contracture develops when the normal tissues are replaced by inelastic fiber-like tissue in an area of the body that isn’t moving. The more you move and stretch, the less likely you are to develop a contracture.

21. How can we prevent it?ROM exercises can help prevent contractures.Sustained stretch provided by bracing can be very effective for improving ROM and decreasing incidence of contracture.AFOs are recommended to help prevent ankle contractures along with night splints that are worn while sleeping.

22. Hand, wrist, and elbow splints can help reduce flexion contractures in the upper extremities.If a contracture develops…Dynamic splinting, serial casting, or tendon release may be recommended.Intervention is only recommended if contracture is inhibiting function, causing skin breakdown, or inhibiting good hygiene.

23. Bracing Options

24. How we treat SpasticityStretching and bracingOral medicationsIntramuscular injections or nerve blocksIntrathecal Baclofen PumpsOrthopedic surgery

25. Oral Medications for Spasticity ManagementSpasticity can also be treated with the use of oral medications. Benzodiazepines, such as diazepam, have been quite popular.BaclofenDantrolene sodiumTizanidine.

26. benzodiazepinesThe benzodiazepines facilitate transmission at GABA-A receptors, one of the principle types of inhibitory synapses in the central nervous system. This results in increased inhibition and reduces monosynaptic and polysynaptic reflexes It is able to act supraspinally and at the spinal cord and has been shown to reduce generalized spasticity, hyperreflexia, and muscle spasmsDiazepam is one of the oldest pharmacologic treatments for spasticity and it is still used today It improves sleep and decreases anxiety. It is an excellent agent for patients who have poor sleep accompanied by night time spasmsSince sedation is one of the most common side effects, dosing usually starts with night time administration and tapers up to two to three doses per day in those who can tolerate it.

27. Pediatric doses range from 0.12 to 0.8 mg/kg/day. For adults, dosing is from 2-10 mg two to three times daily. With the use of diazepam it is important to remember that there is a risk for tolerance and/or dependence with the use of this medication. Diazepam should never be stopped abruptly in patients who have been taking the medicine for an extended period of time due to the risk of withdrawal. Withdrawal symptoms may include agitation, irritability, tremor, muscle fasciculation, nausea, hyperpyrexia, and seizures

28. BaclofenBaclofen is a structural analog of GABA. Baclofen binds to the GABA B receptor which occur both pre- and post-synaptically. The net effect is inhibition of monosynaptic and polysynaptic spinal reflexesBaclofen also reduces the release of excitatory neurotransmitters and substance P when it binds to the GABA B receptors. It primarily acts at the spinal cord level so it is an excellent treatment for those with spasticity of spinal cord origin and it is also used in children with abnormal brain developmentBaclofen has been shown to reduce spasms, clonus, resistance to stretch, and in some cases it has demonstrated an anxiolytic effect Baclofen can often cause sedation so dosing usually begins with night time administration and usually tapers up to three to four doses daily.

29. Pediatric dosing for Baclofen starts between 2.5 and 10mg per day and can taper up to 40 mg per day divided into three or four doses. For adults, dosing starts at 20mg per day and can taper up to 80mg per day divided into three or four doses. Much like the benzodiazepines, care should be taken when stopping this medication. In patients who have been on baclofen for an extended period of time, withdrawal syndromes can sometimes occur. Symptoms of withdrawal may include intensified spasticity with increased spasms, hallucinations, confusion, seizures, and hyperpyrexia

30. DantroleneDantrolene is unique in that it actually acts at the site of the skeletal muscle as opposed to the neurotransmitter systems that most other oral agents act upon. It inhibits release of calcium from the sarcoplasmic reticulum during muscle contractionDantrolene is generally preferred in hemiplegia, traumatic brain injury, or cerebral palsy, but it is also used as a secondary agent in some patients with spinal cord injury. It has been known to reduce clonus and muscle spasms resulting from innocuous stimuli Dantrolene is mildly sedating and may cause malaise, nausea, vomiting, dizziness, diarrhea, and paresthesia The most important side effect is hepatotoxicity. Although its occurrence is rare, liver function tests should be performed before beginning a regimen of dantrolene sodium and monitored periodically. The drug should be tapered or discontinued if enzyme elevations are noted since most cases are reversible upon prompt discontinuation

31. The goal for pediatric dosing of dantrolene is 6-8 mg/kg/day divided into two to four doses per day. The starting dose is usually 0.5 mg/kg/day for seven days and then gradually increased week by week. The goal for adult dosing is 100mg divided into two to four doses per day but dosing usually begins at 25mg/day and then tapers up every week thereafter.

32. TizanidineTizanidine is an alpha-2 adrenergic agonist that acts on receptors in the brain and spinal cordThis causes a decrease in tone through the hyperpolarization of motoneurons. Alpha-2 adrenergic agonists may also have an antinociceptive effect which may contribute to their ability to decrease tone.Some common side effects include sedation, dizziness, nausea, hypotension, and dry mouth. Hepatotoxicity is also a concern when prescribing tizanidine because it is extensively metabolized by the liver. Liver function tests should be checked before initiation of tizanidine and periodically during treatment

33. Pediatric dosing for tizanidine has not been defined but most practitioners start at 2mg at bedtime and taper up to 24-32mg divided in three to four doses given throughout the day. Adult dosing starts at 4mg and may taper up to 8mg three to four times daily.

34. MedicationMechanism of ActionSide EffectsPediatric DosingDiazepamFacilitates transmission at the GABA-A receptors, one of the principle types of inhibitory synapses in the CNS.Sedation, decreased motor coordination, impaired attention and memory. Can cause overdose or withdrawal.0.12-0.8 mg/kg/day in divided doses or once daily at night.BaclofenBinds to GABA-B receptors in the spinal cord to inhibit reflexes that cause spasticity. Sedation, confusion, nausea, dizziness, hypotonia, muscle weakness, and ataxia. Can cause withdrawal.Start at 2.5-10mg per day. Can taper up to a maximum of 40mg per day divided TID or QID.DantroleneActs at the site of skeletal muscle to inhibit calcium release from the sarcoplasmic reticulum.Sedation, diarrhea, and dizziness. Causes hepatotoxicity in 2% so LFTs must be monitored.Start at 0.5mg/kg/day. Can taper up to a maximum of 3mg/kg QID.TizanidineAlpha-2 agonist that acts on the brain and spinal cord to decrease tone through hyperpolarization of motoneurons.Sedation, dizziness, dry mouth, elevated LFTs, insomnia, muscle weakness.Start at 2mg at bedtime. Can taper up to a maximum of 32mg/day divided TID or QID.

35. Intramuscular medicationsNeuromuscular blockade/chemodenervation is another way that hypertonia can be treated quite effectively. Injections of phenol and ethyl alcohol have been used for several decades and in the recent years the use of botulinum toxin has become very popular. Both phenol and alcohol have been used for the treatment of spasticity. In order to localize the nerve that needs to be injected, electrical stimulation is used. This can be painful so sedation or anesthesia is usually necessary, especially in children. The agent is injected perineurally, where it promotes denervation via axonal degeneration. The effect is not permanent, with functional reinnervation occurring over months to years.

36. Adverse effects of both agents include a significant risk of dysesthesia when targeting a mixed nerve, which may persist after the procedure is complete. Other complications may include muscle necrosis or vascular complications. Phenol and ethyl alcohol are excellent, cost effective choices for patients with very powerful muscles that are inadequately treated by the recommended amounts of botulinum toxin. Both types of injections require a skilled clinician.

37. Botulinum ToxinThe introduction of botulinum toxin for the relief of focal muscle overactivity has resulted in a major advancement in spasticity treatmentBotulinum toxin is an exotoxin produced by the bacterium, Clostridium botulinum. The same bacteria that is responsible for tetanus. The site of action for botulinum toxin is at the neuromuscular junction. A protease cleaves one or more vesicle fusion proteins and prevents the release of acetylcholine which causes muscle weakness

38. Its effects on the neuromuscular junction are reversible so reinjection is required every 3-4 months. However, in some patients, the improvements outlast the direct effect on the nerve terminal Dosing is usually 10-12 units per kilogram but not to exceed 400 units in any one procedure in most cases. Two serotypes, A and B, are available in the United States. Type A is marketed as BOTOX by Allergan, Inc. It is approved for cervical dystonia, blepharospasm, hemifacial spasm, primary axillary hyperhidrosis, and strabismus. Type B is marketed as MyoBloc by Solstice Neurosciences, Inc. It is approved for cervical dystonia. Some other off label uses include the treatment of spasticity in those with cerebral palsy, traumatic brain injury, spinal cord injury, and other diagnoses. It is also used to treat sialorrhea and myofascial pain.

39. The most appropriate candidate for botulinum toxin injections is the patient in whom an appropriate weakening of a limited number of muscles has the potential to provide meaningful benefit in care, comfort, or activityThose with adequate selective motor control stand to have the best results while those with long standing contractures and deformities have poorer outcomes

40. Botulinum toxin can also be used for focal and regional management of spasticity in conjunction with orthopedic surgery or in combination with serial casting. Using serial casting in conjunction with botulinum toxin may decrease the amount of time required to achieve the desired range of motion goals

41. MedicationMechanismSite of InjectionOnset and DurationDisadvantages/RisksCostPhenolChemical neurolysis causes denervation via axonal degenerationInjected into the motor points of the involved muscle.Takes effect immediately. Can last 3-12 months.Can be painful and may require anesthesia. Can cause dysesthesias, numbness, or hematoma.Very low costBotulinum type A Presynaptic block of acetylcholine release.IntramuscularTakes effect in 5-7 days. Can last 3-6 months.Lasts only 3-4 months and cannot be repeated in shorter intervals. Can cause swallowing and respiratory difficulties when used in large quantities in the neck muscles.Up to $600 per 100 unit vial

42. Neurosurgical Treatment of SpasticityIn cases where spasticity cannot be managed with physical methods, oral medications, or injectable medications, there are surgical options such as selective dorsal rhizotomy and intrathecal baclofen therapy that can be used. Although these procedures are invasive, they can be very effective in those who have spasticity that is so severe that other methods of treatment have been ineffective or in cases where the side effects of other various anti-spasticity treatments could not be tolerated.

43. In ConclusionAlways keep a goal of care and comfort in mind. When planning for equipment needs and medications, make sure the best interest of the child and family is in the focus.A pediatric physiatrist can typically provide expertise in tone management and equipment/therapy needs. Some pediatric neurologists and developmental pediatricians may specialize in this as well.First line medications such as Baclofen or Valium can be initiated by the pediatrician or pediatric neurologist however, children with Rett need close monitoring for dose adjustments, side effect monitoring, and evaluation of progress towards rehabilitation goals.

44. Neurolytics such as botox and phenol can control the focal tone that can be found in Rett syndrome. Despite aggressive treatment of hypertonia, deformities and contractures can still occur. Decisions regarding the timing of treatments such as botulinum toxin, ITB, or orthopedic surgery should be discussed with the family to see what goals are in mind before proceeding. Management of spasticity with a goal of minimizing its effects and maximizing comfort benefits the child and improves long term functional outcomes.

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48. Thank you for listening!