Why do children with holoprosencephaly have spasticity and how is it treated?
Spasticity seen in various forms of HPE comes from underlying motor control dysfunction. This leads to imbalances in the control of voluntary muscles movements used in such activities as walking. There are several oral medications that can reduce spasticity. These include diazepam (Valium) and baclofen. For certain forms of tightness such as dystonia, medications such as (trihexyphenidyl (Artane) can be useful. Botulinum toxin (Botox®) injection is one way of dealing with the muscle imbalances by weakening selective muscles and changing the balance. There are other ways to approach spasticity. All of these medications have side effects and need careful consideration and monitoring. The field of treating spastcity is evolving quickly and such new approaches as surgery (dorsal rhizotomy) and intrathecal (into the spinal fluid) administration of the antispasticity medication baclofen is now being used in children. A good lay review of the management of spasticity can be found in Exceptional Parent Magazine. They have a web site at www.eparent.com
What is baclofen and how is it used in children with holoprosencephaly? What are the recommended dosage and side effects?
Baclofen is used as a "muscle relaxant" to help decrease muscle tone in children and adults with spasticity from various causes, including HPE. It can be quite helpful for several reasons. If the child is uncomfortable from the high muscle tone for instance, it may help. Also, once muscle tone gets very high, it sometimes can be quite difficult to care for your child. For instance, if the muscle tone in the hips is too high, it could be difficult to open the child's legs to change the diaper. A reason not to use baclofen would be if the child is using the high muscle tone for some function. For example, some children will be able to stand because of the high muscle tone in their legs. Once you take this high tone away with baclofen, they can become more "floppy" and not be able to stand. The good news is, baclofen "wears off", so you can try it, and then stop using it if you're not happy with it. The most common side effect is sedation. For this reason, the dose is usually started off very small, and then increased slowly. This seems to decrease the chances of having this side effect. Also, the sedation is "dose related" meaning that if the child is sleepy at a certain dose, you can try a lower dose.
Can phenol block be used for muscle tightness and spasticity?
Phenol (carbolic acid) creates a chemical nerve block. It is used in adult medicine to treat localized problems of spasticity (high tone or tightness) without the side effects of such anti-spacticity medications taken by mouth as diazepam (Valium). Phenol is an agent that injures the local nerve it has been injected close to. It is important that the injection be close to the nerve of interest. This usually requires electrical studies to locate the nerve and this is painful and difficult for young children to tolerate. It is sometimes done however in children under sedation or general anesthesia. It is important to note that the "block" is really a reversible injury to the nerve. The effects are highly variable and usually last 3-6 months. Side effects of these blocks are usually limited to local discomfort or bruising, but occasionally pain of a more significant nature is seen.
How does one treat sleep disorders in holoprosencephaly?
Many of our children diagnosed with HPE have difficulty sleeping. Chloral Hydrate has helped several of these children. Some parents report that dizaepam (Valium) also helps. These medications may become habit forming and after a prolonged use may lose their effectiveness. There is a non-narcotic alternative called Melatonin. We would recommend that you consult your doctor before using any of these medications.
What is gastroesophageal reflux (GER)?
Gastroesophageal reflux (GER) is basically the movement of stomach contents up through the lower esophageal sphincter into the esophagus. Sometimes GER can lead to frank regurgitation of stomach contents out through the mouth. This is usually differentiated from vomiting. Vomiting occurs with abnormal forceful contractions of the stomach whereas GER occurs with the normal churning contractions of the stomach. Some amount of GER is normal and is considered physiologic or benign. Such episodes are brief, asymptomatic and self-limited. When GER causes symptoms or health problems it is considered pathologic and is sometimes then referred to as gastroesophageal reflux disease (GERD). Most infants have physiologic GER, which is manifested as "spitting up." This is due to the lower tone of the lower esophageal sphincter in infants. Most infants stop spitting up before their first birthday. Children with neurological disorders are at much higher risk of having significant GER that persists past infancy and that is pathologic. There are two major physiologic barriers that normally prevent significant reflux of stomach contents into the esophagus. The first is the functional lower esophageal sphincter (LES), anatomically at the gastroesophageal junction (where the esophagus meets the stomach). The LES should contract when the stomach contracts, preventing stomach contents from refluxing into the esophagus. If the tone of the LES is low, GER is more likely to occur. The second barrier to significant GER is the motility of the lower part of the esophagus. Normal contractions of the esophagus regularly propel refluxed fluid from the esophagus back to the stomach. Abnormal esophageal motility will impair clearance of refluxed material and make GER more likely to be symptomatic and a problem. A third function important to GER is the motility of the stomach. Impaired gastric emptying or gastric dysmotility will exacerbate problems with GER. Impaired emptying of gastric contents through the pylorus into the duodenum can overwhelm the reservoir capacity of the stomach and worsen GER. Health problems due to pathologic GER can be categorized as follows: inadequate nutritional intake leading to poor weight gain and growth, esophagitis (inflammation of the esophagus due to reflux of stomach contents), and pulmonary complications. Poor nutritional intake can be due to excessive regurgitation or decreased appetite from discomfort/fussiness. Esophagitis is due to the reflux of gastric acid and digestive enzymes which erodes the lining of the esophagus. Esophagitis initially causes pain or irritability. Esophagitis can lead to later scarring and stricture (narrowing) of the esophagus or can cause bleeding. Pulmonary complications are due to a number of factors. GER can cause bronchospasm and laryngospasm through a neurally-mediated reflex mechanism. GER can also lead to aspiration of stomach contents into the airway including the trachea, bronchi and alveoli. Chronic micro-aspiration can be a cause of chronic lung disease (coughing, wheezing, increased secretions, decreased capacity). Aspiration of a significant volume at once can cause an acute aspiration pneumonitis (aspiration pneumonia). Aspiration may also be a cause of apnea in some cases. GER, especially while laying down, can contribute to sinus disease, nasal congestion, and ear infections by refluxing into the nasopharynx and causing inflammation. Symptoms of GERD include frequent regurgitation, foul odor to the mouth, excessive salivation, chest pain, fussiness/irritability, poor oral intake, choking, gagging, wheezing, other respiratory symptoms, difficulty swallowing, or bleeding. The possibility of GER as a cause of symptoms can be evaluated through a number of different methods. Occasionally an empiric trial of anti-reflux medication is warranted and symptoms are followed for improvement. A pH probe study can document the presence of GER and can help quantify the severity. An upper GI contrast study can show an anatomic abnormality contributing to GER, identify strictures, and can demonstrate GER, but does not really distinguish between physiologic and pathologic reflux or aid in grading severity. An upper GI endoscopy (EGD) can show evidence of GER both grossly and on pathologic specimens and can aid in evaluating severity. It is important that clinicians try to differentiate between physiologic GER and pathologic GERD and evaluate the significance and severity of GER through history, physical exam and possibly ancillary tests. This evaluation of the significance and severity of GER should guide therapy.
How do you treat gastroesophageal reflux disease?
There are two main categories of medications available to treat GERD, medications which decrease the acidity of stomach contents and medications which improve GI motility (prokinetic agents). Decreasing the acidity of gastric contents will not necessarily decrease the amount of reflux but will likely decrease the severity of complications of GER.
Classes of medications that decrease the acidity of gastric contents include antacids (Maalox, Mylanta, Gaviscon, Tums, Riopan, etc), H2 blockers (Zantac, Pepcid, Tagamet), and proton-pump inhibitors (Losec, Prilosec, and Prevacid). Typically antacids are over-the-counter. They directly neutralize gastric acid. They can immediately relieve symptoms of indigestion and heartburn associated with GERD, and so are most useful in persons who can report symptoms. They have a short duration of action and interact with other medications, so they are not commonly used for the chronic treatment of GERD. H2 blockers antagonize the action of histamine on gastric cells and decrease the secretion of acid and probably digestive enzymes. They are safe medications, can be given just twice per day, and are the mainstay of medical treatment for GERD. Ranitidine (Zantac) and famotidine (Pepcid) generally have been preferred over cimetidine (Tagamet) because they do not affect the metabolism of other drugs as much. Proton-pump inhibitors block the cellular membrane pump which moves acid from cells to the stomach lumen. Losec (Canada) and Prilosec (USA) are the brand-names of the same medication, omeprazole, which is the most commonly used proton-pump inhibitor in children. Omeprazole more completely blocks acid secretion than the H2 blockers, but is usually reserved for cases with severe esophagitis and is not used as routinely for long-term therapy. Lansoprazole (Prevacid) is a newer proton-pump inhibitor which has not been used as extensively, is only available as enteric-coated tablets, and is mainly used in adults for the short-term treatment of ulcers or erosive esophagitis. Prokinetic agents can help decrease GER by increasing LES tone, improving gastric emptying and promoting esophageal and intestinal motility. Prokinetic agents include cisapride (Propulsid), metoclopramide (Reglan), bethanecol, and erythromycin (mainly thought of as an antibiotic but also sometimes has a positive effect on GI motility at low doses). Cisapride is probably the most effective but has recently had bad press due to several deaths from arrhythmias. An arrythmia is more likely when used in combination with certain other medications. Use of cisapride should be avoided with carbamazepine (Tegretol), erythromycin and clarithromycin (Biaxin). Metoclopramide is an alternative to cisapride without the drug interactions, but has more systemic side effects including sedation and dystonia (can make movement problems worse). Erythromycin is increasingly being used for its prokinetic effects.
Besides medications, there are some other things that can help. Giving smaller, more frequent feedings will decrease gastric distension and may decrease GER. Continous tube feedings are an option. Elevation of the head of the bed while sleeping can help, by way of gravity. For severe persistent GERD, there are several surgical options including Nissen fundoplication or gastrojejunostomy. GERD is a common problem in children with neurologic disorders and treatment is not specific for children with HPE. If you suspect that your child has GERD, you should see your pediatrician or a pediatric gastroenterologist. Treatment for GERD should be escalated in a step-wise fashion. Not all GER has to be treated. Treatment should be based on symptoms, severity, and risk of aspiration. Over-the-counter antacids generally are not very effective.
How do you manage excessive saliva and secretions?
Difficulty handling oral and respiratory secretions is a common problem in children with severe motor impairment and children with HPE. Potential sources of mucus are the nasal passages and sinuses, the lungs, and the gastrointestinal tract. Because of oral motor dysfunction, mucus from any of these sources can lead to frequent choking, gagging, and coughing.
It is important to try to determine where the mucus is coming from. Does the mucus being brought up appear to be coming from coughing or retching? This can help distinguish a respiratory from a gastrointestinal source of mucus. Does the mucus have any formula or stomach contents in it? Is his nose also very congested and productive of mucus? Could the mucus be from post-nasal drip?
We find that overnight gastrostomy tube feedings commonly cause increased mucus production. Feedings increase salivation which is normally suppressed while sleeping. The mucus and saliva collects while the child sleeps because of diminished cough and gag reflexes while sleeping. Then the child wakes and goes through fits of coughing, gagging, etc, trying to clear the mucus. Gastroesophageal reflux also can contribute to increased mucus production while being tube fed at night. Sometimes refluxed stomach contents can be aspirated into the trachea and bronchi or can makes its way into the nasal passages and cause an inflammatory response, thus leading to increased mucus production.
Has your child had a Nissen fundoplication? Sometimes a tight Nissen can lead to pooling of secretions in the lower esophagus. When he wakes in the morning, he could actually be vomiting up plugs of mucus that have collected overnight in the esophagus. The can occur in some children with poor esophageal motility, even without previous surgery.
Several ways to handle mucus production during overnight tube feedings: Treat gastroesophageal reflux if present. Elevate the head of the bed. Decrease the rate and/or volume of tube feedings. Provide chest PT, suctioning or nebulizer treatments prior to bed and immediately in the morning. Treat sinus disease if present. If respiratory secretions are a problem, consider ipratropium (Atrovent) or albuterol (Proventil or Ventolin) nebulizer treatments. Ipratropium in some patients is particularly effective. Glycopyrrolate (Robinul) is sometimes effective for decreasing oral secretions, but is a systemic medication. If nasal discharge is a major problem, consider using nasal steroids or nasal cromolyn sodium.
If your child is consistently junky in the morning after an overnight tube feeding, then this needs to be evaluated and adjustments made to the feeding or medical regimen.
What is the difference between Septo-Optic Dysplasia and Holoprosencephaly?
Septo-optic dysplasia (SOD) or DeMorsier Syndrome consisists of small optic nerves, absence of the septum pellucidum, and various other midline brain problems (such as pituitary or hypothalamic abnormalities). Most children are missing part or all of the corpus callosum. While there may be some overlapping features with holoprosencephaly (HPE), in SOD there is no problem with the lack of cleavage of the cerebral hemispheres or the deeper structures.
Some children with HPE have the equivalent of SOD with some additional features. By "labelling" a child with HPE rather than SOD, physicians are referring to a more extensive brain involvement with lack of cleavage between the two cerebral hemispheres and the midline structures that is seen in HPE. In both disorders children may have problems with regulation of sodium and water (diabetes insipidus). The disorders are thought to have different causes and onset during fetal life.
What about melatonin and sleep problems?
Some children with HPE and other neurological disorders have difficulty initiating and maintaining sleep. You should contact your physician about how to deal with this problem. Some have found melatonin to be useful in such children. We are not advocating that you use this medication, but here are some helpful tips if your physician recommends this option. Melatonin is available over-the-counter and can be purchased at just about any pharmacy or General Nutrition Center. It comes in 1mg, 3mg, and 5mg tabs. They can be given by mouth or crushed via G-tube with some water. We usually start with 3mg (in everyone) and then move up or down based on effect. Some children have received up to 15 mg without significant adverse effects. The time required to see an effect is usually about 30 minutes to one hour. Remember that melatonin is not a sedative. Parents are often disappointed after giving a single dose because it didn't seem to work. Parents need to be encouraged to give it regularly, the same time every night. It is more effective after a few weeks rather than immediately.