Investigation of the Disease Progression of Pediatric Patients with Incidental Chiari I Malformation

Grant Recipient: Kerri Thorn, PA-C, Children’s National Medical Center, Washington, DC

Purpose of the study: Some patients are found to have Chiari I malformation after they have an MRI scan of the head or neck to evaluate for another condition. The finding of Chiari I Malformation on the MRI study is considered to be “incidental Chiari I malformation,” which requires no treatment, if symptoms are thought to be unrelated to Chiari I Malformation. The fate of patients with incidental Chiari I malformation is uncertain. Research is required to answer these important questions: 1) What percentage of patients with incidental Chiari I malformation will later develop symptoms and require treatment for Chiari I malformation? 2) Can specific findings on MRI scans predict who will develop symptomatic Chiari I malformation? 3) Are there data to support routine follow-up MRI scanning in these patients?

Researchers at Children’s National Medical Center, Washington, DC, are performing a ten-year retrospective review of their database of patients with “incidental Chiari I malformation” and “symptomatic Chiari I malformation.” They will evaluate whether patients with the diagnosis of incidental Chiari I malformation developed symptomatic Chiari I malformation during that time period. The study will also compare symptoms and MRI findings of patients with incidental Chiari I malformation with those of patients with symptomatic Chiari I malformation and evaluate for factors that predict development of symptomatic Chiari I malformation. The project has already received Investigational Review Board (IRB) approval. Kerri Thorn, PA-C., is the Principal Investigator on the project and her Associated Investigators include a pediatric neurosurgeon and a physician assistant. An ASAP Grant has been awarded and research will start immediately.

The Genetics of Chiari Type I Malformation (CMI) with or without Syringomyelia

Grant Recipient: Dr. Allison Ashley- Koch, Duke University

Purpose of the study: The Duke Center for Human Genetics is investigating the hereditary basis of Chiari type I malformations (CMI) with or without syringomyelia.  Our research is aimed at learning if CMI is indeed caused by factors inherited through the family and, if so, which genes are involved.   The long-term goal is to find out how these genetic factors cause or contribute to CMI, with the hope that this knowledge will lead to improved diagnosis and more effective treatments.

Participation: We are actively recruiting families who have TWO OR MORE family members with Chiari type I malformations, with or without syringomyelia. These family members must be related to each other by blood, and BOTH must be willing to participate. At the current time, we are NOT accepting families in which the only diagnosed members are a parent and child.

Study participation involves these steps:

  • Contact our study coordinator
  • Answer questions about family and medical history
  • Complete a medical questionnaire
  • Provide a photo of yourself
  • Allow review of medical records and MRI to confirm the diagnosis
  • Provide a blood sample
  • Potentially ask other family members (parents, siblings, children) to participate in the study.

If your family meets these criteria and you want to receive study participation information, please contact the study coordinator at chiari@chg.duhs.duke.edu or call toll-free at 1-877-825-1694.

Funding provided by the Marcy Speer Research Memorial Fund

Outcomes in Patients Undergoing Surgical Intervention for Chiari Type I Malformation with Syringomyelia

Grant Recipient: Bermans J. Iskandar, MD, University of Wisconsin at Madison, Tim M. George, MD, University of Texas at Austin Sponsored by the American Society of Pediatric Neurosurgeons

Grant Amount: $210,000 ($105,000 per year)

Purpose of the study: This is a pilot study that aims to determine the feasibility of large, federally-funded, multicenter trials in Chiari I and syringomyelia. The hope is to give this type of rigorous research in the Chiari/syringomyelia field a “kick-start” nationally and internationally, so that we can ultimately minimize controversy and start answering fundamental questions.

The experimental methodology consists of prospectively collecting clinical and radiographic data, thus allowing the establishment of study protocols to evaluate surgical approaches and outcomes of patients with Chiari I and syringomyelia.  By recruiting children with documented Chiari I and syringomyelia at several institutions that differ in their surgical approaches, the investigators will attempt to compare the results of the three main surgical techniques: 1) Bone decompression;2) Bone decompression with duraplasty; and 3) Bone decompression with duraplasty and tonsillar shrinkage.

For the purpose of objectivity, the main endpoint will be resolution of the syrinx.  However, the study will also collect data on the clinical and other radiographic characteristics (e.g., extent of tonsillar descent, cine flow, etc.) of patients who ultimately undergo surgical intervention. This information will be used to determine whether any of these characteristics predict favorable surgical outcome.

This long-overdue prospective multicenter trial, which is a direct result of an ASAP member survey, would be the first of its kind for these disorders.

Pain Management in Patients with Chiari I and Syringomyelia

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Ann Berger, MD, MSN, Chief of Pain and Palliative Care, National Institutes of Health

Treatment of Children with Chiari and Syringomyelia

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Robert Keating, MD, Chief of Neurosurgery, Children’s National Medical Center
ASAP Medical Advisory Board

Techniques and Problems of Craniovertebral Fusion for Craniocervical Instability and Hindbrain Herniation

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Arnold Menezes, M.D. Professor and Vice Chairman, Department of Neurosurgery University of Iowa
ASAP Medical Advisory Board Chair

Sleep Disordered Breathing and Sleepiness in Patients with Chiari type I Malformation

by Dr. Watson, Assistant Professor of Neurology at the University of Washington (UW) and Co-director of the UW Sleep Disorders Center at Harborview.

When I’m talking about sleep disordered breathing, I’m talking about sleep apnea mostly, which is a term that you all may be familiar with.  Sleep apnea is basically having problems with breathing during sleep at night.  There are multiple types of sleep apnea.  There is obstructive sleep apnea – where there’s a blockage of tissue keeping you from breathing effectively.  There’s central sleep apnea – where your brain is not telling the body to breath in your sleep.  Then there are milder forms of obstructive sleep apnea which are similarly a result of blockages in breathing, what we call respiratory effort-related arousals.  I’ll talk more about that and give you more background.

The relationship between Chiari Malformations and respirations is actually fairly complex.  The way that we breathe is our brain samples carbon dioxide and oxygen from the blood as it goes through our brain stem and it adjusts our breathing level accordingly.  When we’re awake we have a wakefulness drive to breathe, so we can remember to breath and we can cause ourselves to breathe when we’re awake.  When we’re asleep our breathing is totally dependent on our brain stem measuring specific carbon dioxide levels and oxygen levels.

Chiari Malformation and RespirationThese areas here, [see Figure 4] you can see in the brain stem, the Dorsal and Ventral Respiratory Group and the Pontine Respiratory Group.  These are the areas that have these cells or these chemo-receptors that take these measurements and then tell the body to breath.  You can imagine that all the pressure that’s going on in this region in patients with Chiari Malformations that this affects the functioning of these cells.  So that’s what happens.  They don’t measure these blood gases as well as they should and therefore breathing is affected.

cranial nervesThere are some other things going on as well.  [see Figure 5] Cranial nerves that are coming out of this region that sub-serve muscles of the tongue and the throat can be stretched and affected.  That can cause your throat to become floppy and collapse in on itself also causing problems breathing in your sleep.  Lastly there are nerves that send signals from the lung stretch receptors and also what’s called the carotid body and the aorta that are also monitoring these blood gases.  So those nerves can be affected as they’re feeding information to this area.  The signals that come out of here to the diaphragm and the other muscles that breathe can also be affected, particularly by people that have co-morbid syringomyelia.  So it’s really a problem with blood gas sampling, it’s a problem with the output of these centers to control breathing and a problem of the sensory input that tells the brain what’s going on with the rest of the body as far as breathing is concerned.

This is a diagram [see Figure 5] that is showing you the nerves that would be involved that would be stretched and causing problems.  We have 9, 10 and 12.  The Glossopharyngeal nerve sends motor output to the upper pharyngeal muscles here and what’s called the Stylopharyngeus muscle which also helps keep the airway open.  The Vagus nerve, the tenth nerve, sends motor output to the lungs so it helps control breathing and also the pharynx and larynx; so again here in the throat region.  Then the Hypoglossal nerve, the twelfth nerve, controls motor activity in the tongue.  That’s important because people with obstructive sleep apnea will often have a tongue that can fall back into your airway when you lie on your back and block air flow.  Stretching and damage to these nerves can cause problems.

obstructive sleep apneaLet me talk a little bit more about the two different kinds of sleep apnea, the obstructive sleep apnea and the central sleep apnea.  Obstructive sleep apnea as a sleep position is by far the most common type of sleep apnea that we see.  What we have here is 120 seconds of an overnight polysomnogram, [see Figure 6] which is a sleep study which some of you may or may not have had.  Just to go through these channels to let you know what we’re looking at in this colorful picture.  This is measuring brain waves to tell you what stages of sleep you’ll be in during the night.  Then you have this, measuring eye movements, which helps us stage sleep as well.  A chin tone, which is muscular tone in the chin, helps us tell what sleep stage you’re in.  We look at snoring; we look at chest and abdominal movement.  This is very important because this is telling us whether or not a person is trying to breathe.

What to expect after surgery For Chiari I with syringomyelia

Transcriptions from an ASAP teleconference presented by Dr. John Heiss, National Institutes of Health, Bethesda, Maryland.

Good evening.  I was invited to spend about 15 minutes discussing a topic that might be of interest to ASAP members, so I chose to speak about what a typical patient with Chiari I and syringomyelia can expect after surgery.  I am going to talk about this is the context of 29 consecutive patients that we treated at the National Institutes of Health.  We published our work this January in the Journal of Neurosurgery—I hope that some or most of you received a pdf-version of the paper from Patricia by email.

Let me give you some background.  We performed the study to find out how long it would take for a syrinx to become smaller after surgery.  We enrolled patients into the study who had syringes* that were large enough to distend the spinal cord, with the average diameter of a syrinx being about 7 mm, which is about 2/3rds of the diameter of a normal spinal cord.

We chose a reduction of 50% in syrinx diameter as our primary outcome measure because this amount of reduction in syrinx diameter would indicate that the syrinx was no longer distending the spinal cord.  We were also interested in what happens over time after surgery to major symptoms of syringomyelia such as weakness, numbness, and dysesthetic (neuropathic) pain.

All patients gave their informed consent to participate in the research study.  The research study was approved beforehand by our Institutional Review Board, which is a committee that evaluates protocols to see if the research is scientifically sound and that it does not expose patients to unnecessary risk.

For the research study patients with Chiari I and syringomyelia came to the Clinical Center of the National Institutes of Health in Bethesda, Maryland for their evaluation and treatment.  Patients were 16 to 61 years of age. Patients underwent MRI scans of the neck before surgery; the diameter of their syringes was measured using a computer workstation.  We also recorded a medical history and a neurological examination.

We specifically noted the presence and severity of signs and symptoms such as weakness, atrophy (wasting of muscles), spasticity (tightness of muscles), ataxia (unsteadiness while walking), pain and unpleasant sensations in the torso or extremities (dysesthetic pain), and loss of sensation.

Of course the MRI scan and a history and neurologic examination are standard studies for all patients who are being considered for surgical treatment of the Chiari I malformation and syringomyelia.  The reason that they could be used for research in our study was because of the way in which these tests were applied:

  1. It was decided before the study began that all patients would have the same type of MRI study and that all patients would have their neurological examination recorded in the same manner;
  2. The research was designed so that information from the MRI scans and examinations was entered as each person was examined (prospectively) rather than from a retrospective analysis of charts on patients who had completed treatment;
  3. Tests such as the MRI scan, history, and neurological examination were performed in the same way after surgery as they were before surgery and were repeated at specified intervals (1 week, 3-6 months, 1 year, and yearly) after surgery.

performed the same surgical procedure, craniocervical decompression and duroplasty, on all patients in the study.  The average period of follow-up after surgery was 3 years.  The number of MRI scans and examinations that were performed on each patient as part of our study exceeded the number that would be performed on the basis of clinical care.

We found that by 6 months after surgery that all but one patient reported improvement, and that the patient who did not improve reported that he was stable.  In all but 4 patients the syringes became less than one-half of their original diameters by 3-6 months after surgery.  By 2 years after surgery all syringes had become less than one-half of their original diameters.  The length of the syringes also became progressively shorter after surgery compared to before surgery.

We observed that in 12 patients (41%), the syringes did not disappear completely.  There was no difference in outcome in patients without complete disappearance of their syringes compared to patients with complete disappearance of their syringes.  It was remarkable that a minority of patients became free of symptoms after surgery, only 22% at 3 months, 29% at 1 year, and 32% at 2 years after surgery.  Residual signs and symptoms arose from residual dysfunction of the spinal cord.  The most frequent signs and symptoms that persisted after surgical treatment were painful dysesthesias (neuropathic pain) and loss of sensation, which were found in about one-half of patients.

Our conclusions from the study were that

  1. Almost all patients notice some improvement after surgery
  2. Many patients experience residual symptoms, especially dysesthetic (neuropathic or chronic) pain and loss of sensation
  3. All syringes will become smaller over time after successful surgery, although many will not disappear completely
  4. Patients that have reduced-size but not complete disappearance of their syringes had similar clinical outcome compared to patients with complete disappearance of their syringes.

We do not believe that a small, collapsed syrinx will cause further injury to the spinal cord.  We do not recommend additional surgery in patients whose syringes become smaller but do not resolve completely after surgery, because symptoms and signs reflect injury to the spinal cord that the syringes produced before surgery and not ongoing injury to the spinal cord.

Pregnancy and Chiari Malformation with or with out syringomyelia

by Diane Mueller, ND, RN, C-FNP

The reason I became very interested in this due to the frequency of times I was having this discussion not only clinically but on the telephone or over the Internet: is it safe to plan a pregnancy when you have Chiari? Is it safe to have a vaginal birth? Should I have a c-section? I’ve even been contacted by many health care providers, asking if it safe for the patient to have a vaginal delivery. And what I found was there was very little literature to support either having a vaginal delivery or epidural.

pregnancy-figure-1When I went back to review some of the literature, I found some very old studies that cited patients who were studied without diagnosis of Chiari or syrinx, so keep in mind these are general population studies and most of these studies were done before 1965. I couldn’t find anything in the literature that was really very recent. What I did find in the literature was that pain during labor had the greatest effect on CSF pressure, but that wasn’t really surprising and I’m sure it’s not a surprise to any of you to hear that. But was surprising to me was, during an active phase of labor, it raised almost 700mm of water [see Figure 1], that’s a significant increase in CSF pressure.

Certainly that would make anyone be concerned about intracranial pressure or intraspinal pressure during an active phase of labor. The studies did support epidural anesthesia during contractions to control pain. So pain control during contractions was one of the most important factors in controlling CSF pressure during active labor. Once again these are patients who were studied who did not have diagnosis of Chiari or syringomyelia at the time of delivery.

pregnancy-figure-2Then I went on to review the literature for patients who had been diagnosed with Chiari and also had a pregnancy either planned or unplanned. What I found again were very few documented articles in the literature. There were a few scattered notes of single case reports beginning around 1994/1995, the most recent one was reported in 2002 [see Figure 2], and this was a report of 12 patients who were studied who had the diagnosis of Chiari malformation. There was not a mention of the patients having syringomyelia, which I thought was interesting, but they did report they had Chiari malformation. They delivered with either epidural, local anesthesia or general anesthesia.

The general anesthesia was for the c-section, and none of the women out of that 12 were reported either worsening or developing new symptoms either during pregnancy, during delivery or postpartum. So this was an encouraging study I found because first it was the largest case study I could find, 12 women. And it showed that there was either no new development of symptoms or worsening of symptoms and certainly no complications reported either during pregnancy or during delivery.

This is one of our beautiful baby girls who was born to a young woman in Rochester, NY. She was about 26 years old when she had her surgery; she had about a 9mm herniation and a very large cervical syringomyelia. She did very well after surgery, and the syrinx actually resolved 3 months later on MRI. This baby was born about 13 months after her decompression surgery. She did absolutely fine during her pregnancy; she had no new symptoms. She had no symptoms during labor; she labored for about 3 ½ to 4 hours, and she did have an epidural injection during labor. She had no problems related to the delivery, and has had no problems since. She did very well and as you can see normal healthy beautiful baby girl.

pregnancy-figure-3

[see Figure 3] I don’t have time to go over each case individually, so I’d like to just summarize the 6 patients we followed prospectively during their pregnancy and talk about each in summary.

We followed 6 young women average age of 27 years, so the range of age for these folks was 23 to 31 years of age. The average amount of herniation was 8mm in this group. The most common reported symptom at presentation to us was headache, which is very typical and classic of Chiari malformation. There were 3 women, one with a syrinx who delivered after they were diagnosed with Chiari malformation but before they had surgery. These are women who had a pregnancy after diagnosis but before decompression surgery. We had 3 women, again one with a syrinx, who delivered after posterior fossa decompression. These are women who were diagnosed, had the decompression surgery and then delivered after their surgery. Of course, they were not pregnant during their surgery. We had 1 c-section and 5 vaginal deliveries. 2 women had epidural anesthesia, had absolutely no problem with epidural anesthesia, had no complications, and did not report an increase in symptoms because of the epidural anesthesia.

We had 1 woman who had an intrathecal anesthesia for a c-section. She delivered triplets. I’m going to be talking about her in just a little bit. She’s a very unique case for us and probably for most of the people who follow Chiari patients. We had 1 woman who reported depression, tachycardia and hypertension, all of which were worse during the second and third trimester of her pregnancy; however, they’ve since resolved after delivery.

It would be interesting to ask if the depression, tachycardia and hypertension were due to the pregnancy, or because of the Chiari malformation? This woman had not had surgery yet so it’s difficult to say what came first, the pregnancy that caused this or the Chiari malformation that aggravated it. We had 2 women who reported significant improvement in their headaches during pregnancy. It’s hard to explain that if the intracranial pressure and the intraspinal pressure increased. It’s hard to explain how the headache actually improved during pregnancy, but these are self-reported symptoms that had improved.

We then had 3 women who reported no change or worsening of their symptoms during pregnancy, during delivery or postpartum. When we looked back through our series, of a little over 300 patients, we did note that quite a few of the patients had reported either their symptoms starting during a pregnancy, starting during delivery or starting shortly thereafter. And in looking a little bit closer at these, these are 12 additional patients, these are not out of those 6, those 6 are in addition to. We had 2 whose headaches began during the pregnancy; they can actually remember, “Gosh, I was fine up until I was pregnant with my second child. All of a sudden I started having symptoms.” We had 3 patients whose headache was worse during the pregnancy. In other words, they had the headache prior to pregnancy, but for some reason the symptoms became worse, and that was the 3 out of those 12.

We had 5 patients who said their headache became significantly worse after epidural anesthesia for vaginal delivery. We had 1 patient who had a headache that became worse after delivery but not an epidural anesthesia, so for some reason the intracranial pressure increased and the headache became worse. And then we had 1 patient whose headache recurred. She had already been decompressed, had a decompression procedure, by the way, not with us. Her headache recurred after her first pregnancy. So she had Chiari malformation decompression and then her headache did recur after her first pregnancy and that again was a little bit different.

A couple of conclusions that we can draw and certainly by no means are there conclusions based on every individual patient, if you’re planning a pregnancy, you need to talk with your individual providers and make sure that they understand Chiari, that they understand syringomyelia and that they understand that complications can present themselves.

In our series with these 6 patients, we had no patients who reported significant increase in symptoms during and after delivery. We had no complications of epidural anesthesia as related to Chiari. Now that’s not to say patients didn’t have a wet tap and have to have a blood patch afterwards. These are symptoms related directly to Chiari, whether they had previous surgery or not.

Again, the true risk of intracranial pressure or intraspinal pressure with intrathecal or epidural anesthesia really remains uncertain. I could not find in the literature any case reports that specifically stated there was a problem with vaginal delivery, epidural anesthesia or intrathecal anesthesia related directly to Chiari; and in our series, we had none. But again, it’s important to talk with your provider about the Chiari malformation. Make sure your OB/GYN understands the disorder, understands the complications that could arise, and you can share this information with that person.

Just to look at a couple of other little babies who have been born. This is a wonderful little baby who was born in Missouri. Mom had a normal vaginal delivery, had no problems during pregnancy and certainly no problems during delivery, and as you can see, it’s a normal healthy little girl.

And this little one,  you can see has no problems with laughing, laughing doesn’t cause her any problems with headache, and any picture you see she is laughing just like that, so, fortunately, normal healthy babies that have been born.

This is a bit of a unique case. This was a young woman who we saw originally back in 1999. She was one of our medical students at the University. She had been diagnosed somewhat incidentally; she had been having some headaches, kind of blew it off to stress during school, kind of made all kinds of excuses for these headaches she was having. She did finally have an MRI and was diagnosed with Chiari malformation; she had 5mm herniation. We saw her and she was really not that troubled with her symptoms at the time. She wanted to finish school. She didn’t feel she needed surgery at the time. She did not have a syrinx. So we followed her for about a year and a half. Close to the 4th year of her medical training, she started to develop swallowing problems. And really declined in a very rapid fashion, began having aspiration, began choking on food and liquids and really started to get herself into trouble. She did elect then to go ahead and have decompression surgery. She did very well; again she did not have syringomyelia at the time of diagnosis or at the time of surgery. She was able to finish medical school, she went on to start a family practice residency and shortly after about 4 months after she started her family practice residency, she decided that she was doing so well, she wanted to go into OB/GYN and that was her dream to begin with was to OB/GYN. So she did do that, she ended up moving to another state, she went into an OB/GYN to start her residency and had a planned pregnancy. [see Figure 8] She didn’t plan on 3, she did plan on 1 but she didn’t plan on 3 and that was a bit of a surprise to her. She did very well during her pregnancy. She did have a c-section; she did not have vaginal delivery because of the increased risk to the babies, being multiple births. She did not have it because of Chiari malformation or because of her surgery, she did have a c-section, she had an intrathecal injection prior to delivery of the babies, did absolutely fine. Had no symptoms during the pregnancy. Even with carrying triplets, she had no related symptoms, she has had no related symptoms since then.

Diane Mueller, ND, RN, C-FNP
Department of Neurosurgery
University of Missouri at Columbia
One Hospital Drive NSG N521
Columbia, MO 65212-0001

Chiari and Syringomyelia 101

by John Oró, MD

A Brief Look at Neuroanatomy

The brain is enclosed and protected by a rounded skull made of rigid bone. The bottom of the skull contains multiple openings called foramen through which nerves and blood vessels pass. The inside of the skull, called the intracranial space, is partly separated into two compartments by a tent like structure called the tentorium. The large compartment above the tentorium is called the supratentorial compartment and the compartment below the tentorium is called the infratentorial compartment. (Supra means above, and infra means below.) Most doctors call the infratentorial compartment the posterior fossa.

The supratentorial compartment contains the two halves of the cerebrum known as cerebral hemispheres. The hemispheres come together in a deep central area called the diencephalon. Through an opening in front of the tentorium, the diencephalon connects to the brain stem. On the back of the brainstem sits the cerebellum. The brain stem continues through an opening at the bottom of the skull, called the foramen magnum, and connects with the spinal cord. The spinal cord runs in the spinal canal.

figure1

There are four cavities filled with spinal fluid within the brain called ventricles. [see Figure 1] Two large C-shaped ventricles, called the lateral ventricles, are located within the cerebral hemispheres and are connect by two small tunnels (the foramen of Monro) to the third ventricle. From the third ventricle spinal fluid flows through a small tunnel known as the Aqueduct of Sylvius to the fourth ventricle which is located between the brain stem and the cerebellum. Spinal fluid flows out of the fourth ventricle through three openings: two openings at the side of the fourth ventricle called the foramen of Luschka and one at the bottom of the fourth ventricle called the foramen of Magendie. From these three foramina spinal fluid flows out of the ventricular system to the surface of the brain as well as down the spinal canal and back up. Spinal fluid is created by a tuft of vascular tissue called the choroid plexus that is present within each ventricle. With every heartbeat, blood passing in the choroid plexus is filtered to create a clear colorless fluid that looks like water called cerebral spinal fluid or CSF. The spinal fluid flows down through the ventricles, exits the through the three openings of the fourth ventricle, and flows around the brain and spinal cord. The spinal fluid is taken back up in the vascular system through a large vein located at the top of the brain called the sagittal sinus. By way of special connections called arachnoid granulations, the spinal fluid drains into the sagittal sinus. Here it becomes part of the blood that drains through the jugular veins to the heart. With each heartbeat, a small amount of spinal fluid is created inside the ventricles at the same time a small amount is taken up by the veins, keeping the system in balance.