Rett Syndrome Treatment & Management

Updated: Feb 06, 2017
  • Author: Bettina E Bernstein, DO; Chief Editor: Caroly Pataki, MD  more...
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Treatment

Approach Considerations

To maximize the abilities of patients with Rett syndrome (RS) requires the adoption of a comprehensive team approach.

If seizurelike activity is noted, video-electroencephalographic (EEG) monitoring may be necessary to identify epileptic seizures for which antiepileptic drugs (AEDs) are appropriate. The vacant spells noted in RS patients may not be seizures, and seizures may be less common than reported. However, true seizures may go unrecognized during sleep.

Various treatments have been used to manage epilepsy in persons with RS. Treatments range from conventional AEDs (eg, carbamazepine and valproic acid) to newer AEDs (eg, topiramate and lamotrigine), a ketogenic diet, and vagal nerve stimulation.

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Pharmacologic Therapy

No medications are available to treat persons with RS. Bromocriptine and carbidopa-levodopa, which are dopamine agonists, have been tried as treatments for motor dysfunction in persons with RS; however, benefits are neither substantial nor long lasting. Case reports have suggested that levocarnitine may be effective. Double-blind placebo-controlled trials of folate and betaine have not demonstrated objective evidence of improvement, despite the theory that methyl-group pools might promote transcriptional repression. [37]

Individuals with gastroesophageal reflux (GER) may respond to conservative medical treatment with antireflux agents (eg, metoclopramide), thickened feeding solutions, and semiupright positioning at bedtime. AEDs may be prescribed to control seizurelike activity.

Sarizotan, a 5HT1A agonist and D2 agonist/antagonist, has been associated with a 70-85% reduction of apneas and hyperventilation episodes in preclinical testing with both acute and chronic dosing. [38] Sarizotan has been designated orphan drug status by the U.S. Food and Drug Administration and the Committee for Orphan Medicinal Products (COMP) from the European Medicines Agency (EMA).

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Nonpharmacologic Therapy

Vagal nerve stimulation has generally been safe and well tolerated, with few surgical complications, increased alertness, and improved ability to participate in activities. [39]

If seizures are well controlled, addition of the Snoezelen multisensory approach, with or without hydrotherapy, may be considered. [40, 41, 42]

If an RS patient cannot manage oral intake of food, a gastrostomy tube may be placed to minimize the risk of aspiration or recurrent pneumonias. Many girls with RS may experience significant somatic growth failure. Female RS patients aged 4-8 years may demonstrate poor or no weight gain despite apparently adequate caloric intake. In such cases, supplemental feeding is warranted, either orally or via a gastrostomy tube.

If GER is refractory to medical treatment, a fundoplication may be necessary.

Scoliosis in individuals with RS often does not respond to orthotics. Surgery should be considered in patients with Cobb angles more than 40-45° or curves that cause pain or loss of function. [43]

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Diet

Many RS patients experience poor weight gain, despite excellent appetites. Improved weight gain and better seizure control have been reported when girls were given a high-calorie diet, with approximately 70% of calories from fats and 15% each from carbohydrates and proteins.

Osteoporosis is common in persons with RS. Treatment with vitamin D, calcium supplements, and bisphosphonate may be warranted.

The ketogenic diet may be helpful in patients with epilepsy that does not respond to usual pharmacologic treatments. Its utility in epilepsy syndromes of various etiologies suggests that this approach may have multiple mechanisms of action. [44]

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Activity

Therapy that promotes ambulation, balance, and hand use is important. Hand splints and other devices that decrease hand stereotypies may make girls with RS more focused and may decrease agitation and self-injurious behavior. Hinged ankle-foot orthoses and physical therapy may be beneficial in treating toe walking that results from increased heel cord tone.

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Consultations

Optimal management of RS involves early multidisciplinary evaluation and treatment, including communication assessment, oral motor assessment, and various other assessments and therapies.

Most girls with RS lose expressive language; however, some may retain 1-word expressions, and others may attempt to communicate through eyes and body language. Careful assessment of the patients’ communication abilities and the parents’ response to the patients’ communication is important for maximizing the potential of individuals with RS. Devices such as picture boards may be helpful.

Feeding disorders occur in more than 80% of RS patients aged 4-8 years. Causative factors include abnormal tongue movements and tone, skeletal misalignment, and rigidity, [45] underscoring the importance of oral motor assessment. Treatments may range from simple positioning and rigidity-decreasing therapy to more complex interventions.

Music, hydrotherapy, hippotherapy (ie, horseback riding), and massage are sometimes helpful. Other needs include psychosocial support for families and the creation and implementation of an appropriate educational plan with schools. Parents may require help in accessing community resources for items (eg, wheelchairs or ramps) and services that allow home care of RS patients.

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Long-Term Monitoring

Issues that may have to be addressed in long-term management of RS include the following:

  • Agitation and screaming
  • Sleep disturbances
  • Constipation
  • Scoliosis
  • Osteopenia with possible fractures
  • Birth control

Perhaps reflecting attempts to communicate, agitation and screaming are common and are often distressing to families. RS patients need gradual transitions and may find it very difficult to communicate physical problems to physicians. The clinician should perform careful evaluation to exclude clinical problems and pain. If no clinical reason for the agitation can be found, treatment may include warm baths, massage, music, or a quieter and less stimulating environment.

For management of sleep disturbances in RS, short-acting nonbenzodiazepine receptor agonists (eg, zaleplon and zolpidem) may be helpful without exerting untoward effects on daytime functioning. Other approaches to sleep problems have included the administration of melatonin 2.5-7.5 mg and the application of behavioral techniques.

Constipation is common in RS patients. Treatment involves adequate fluid intake, high fiber intake, and exercise. Stool softeners may be necessary; however, continuous laxatives, suppositories, and enemas must be avoided. Long-term mineral oil use interferes with the absorption of certain fat-soluble vitamins. Regular oral milk of magnesia can be used.

Scoliosis occurs in more than 50% of RS patients, usually between the ages of 8 and 11 years. It may progress rapidly, especially if early hypotonia, dystonia, or loss of ambulation is present. Close monitoring is necessary to determine whether bracing or surgery is needed.

Osteopenia with possible fractures may occur for multiple reasons; it can be minimized through physical therapy, good nutrition, and close observation. [46]

In most girls with RS, puberty occurs at the same age as it does in girls without RS. Discussions regarding birth control should be held with the patient’s guardians.

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Deterrence and Prevention

A study done in Italy of 164 patients analyzed immune function as stratified between three groups: those with Rett syndrome (RS), those with nonRS pervasive developmental disorders, and healthy controls, and found that RS patients could be distinguished from the other groups by a consistent and significant increase of the serum IgM fraction via antibody agglutination and correlated with the CSF114 (Glc)-based assay. This suggests that this change might reflect a common underlying mechanism involving neuroinflammation either as a cause or an effect of the immune dysfunction to other neurological diseases such as observed in multiple sclerosis, meningitis, and encephalitis. [47]

A 2014 study using MeCP2 gene knockout mice showed that earlier identification of RS might be possible with detection of subtle gait parameter changes as reflected by changes in treadmill overlap distance, stance width, step angle, and gait symmetry. [48]

Another study using MeCP2 gene knockout mice suggested that prevention of seizures due to RS might be possible as MeCP2 deletion from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. This is possibly related to the reduction of the number of GABAergic synapses in the cortex and enhancement of excitability of layer 5 pyramidal neurons with GABAergic transmission reduction in neurons without MeCP2 due to the role that MeCP2 plays in cortical excitatory neurons regulating GABAergic transmission and cortical excitability. [49]

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