conquer
c hiari
Working Towards a Comprehensive Chiari Theory:
Five Important Research Questions
November 2013 - Later this month, there will be a milestone meeting at the Conquer Chiari Research
Center. This meeting represents a milestone, because of the diverse disciplines of those attending. In
addition to the CCRC team, there will be faculty from other departments of the University of Akron, and
surrounding hospitals and universities. The participants have expertise in, to name a few, psychology,
education, mathematics, diet/nutrition, metabolics, community health, biology, chemistry, electrical
engineering, and mechanical engineering. It is safe to say that never before has such a broad range of
disciplines gathered to talk about Chiari. Participants will present updates on current projects, proposals
for new projects, and general thoughts and ideas on Chiari research (please note this is an invitation only
professional meeting, there will continue to be CCRC Open Houses for the Chiari community).
As I considered how to open this meeting, I decided to challenge the participants and the CCRC in general,
to begin to develop a comprehensive theory of Chiari. Such a theory would spell out, in detail how Chiari
forms in different patients, how it can affect them, and what can be done to alleviate and prevent it.
Developing such a theory would go a long way to achieving Conquer Chiari’s mission and would
undoubtedly improve the experiences and outcomes of patients.
So how does one go about building such a theory? By asking specific questions. Following are five
important, but not exclusive, questions that if addressed adequately would lay the foundation for a strong,
invaluable, theory of Chiari.
1
Is there a better way to assess Chiari than tonsillar herniation?
Since Chiari is currently defined by measuring tonsillar herniation, this question really gets to the
heart of what Chiari is. It has become common knowledge in the patient community that tonsillar
herniation is not well correlated with symptom severity or clinical outcome, but there is also a lot of
misunderstanding regarding this statement.
Research has found that among groups of symptomatic Chiari patients, the extent of herniation does NOT
correlate well with pre-surgical symptom severity or with post-surgical outcomes. In addition, research has
clearly shown that not everyone with herniations greater than 5mm have symptoms (or ever will), and
some people have symptoms with herniations smaller than 5mm.
That does not mean we just throw out tonsillar herniation completely – at least not yet. It is important to
keep in mind that a large herniation is still the best indicator of symptoms consistent with Chiari. In a group
of people with 10mm herniations, a larger percentage will have symptoms consistent with Chiari than in a
SM
group of people with 5mm herniations. Along those lines, in a group of people with minimal herniations (12mm), only a small percentage will have Chiari type symptoms, while most will be healthy. Therefore it is
not that tonsillar herniation is not useful, but rather that it is not always enough, especially with the
widespread use of MRIs, to diagnose Chiari. And further, it does little to help address the issue of
objectively evaluating whether surgery was successful.
What is needed are additional quantitative measures in order to:
•
•
•
Help diagnose patients whose symptoms are not obviously due to Chiari
Help people who are diagnosed incidentally, or secondary to a head trauma, understand if they are
likely to ever develop symptoms, or if they even have Chiari at all
Assess patients after surgery who have residual symptoms
This is a primary focus area of the Conquer Chiari Research Center (CCRC) and work is ongoing, trying to
identify parameters to help physicians.
In general, but not exclusively, the research is focusing on two areas. First is hydrodynamics, which refers
to the flow of the CSF in the brain and spine. CCRC researchers are using sophisticated engineering
techniques to look at hydrodynamic properties, calculated from MRIs of Chiari patients, versus healthy
people, and Chiari patients before and after surgery. The Second area involves morphometrics, or the size
and shape of the skull base and brain. In other words, are there measurements, either instead of or in
addition to, tonsillar herniation, which would be useful to clinicians in either diagnosing Chiari or evaluating
surgical success.
When we do find these measures, in addition to the clinical impact they will have, it should also provide
more clues to answering the next big research question….What causes Chiari?
2
What causes Chiari?
One of the frustrating aspects of Chiari is the wide variety of symptoms and problems which can
manifest. Is this a reflection of the importance of the brain structures involved, or is it an indication that
Chiari is more than just tonsillar herniation?
Certainly, we know that there are patients who have other issues, such as EDS, intractranial hypertension,
etc., but how are these related? Did they cause the tonsillar herniation, did the herniation cause the CSF
issues, or are they both a reflection of a more fundamental problem? And what of the related issues that
seem symptomatic to Chiari, such as neck and shoulder problems, and even headaches, could be a
reflection of something more. Do those with Chiari also have abnormal musculature, vasculature, and/or
nervous systems? If Chiari can be traced to problems in the womb, does that mean that some, if not all,
Chiari patients have more systemic issues, or can it be narrowed down to the skull base area?
The answers to these questions likely vary among patients and its seem reasonable to assume that there
are different sub groups of patients for which it would make sense to research, and even treat, differently.
Many diseases have subgroups of patients who encounter different symptoms and respond to different
treatments.
While we are far from answering whether Chiari is a more systemic problem, we are getting closer to
peeling back ONE layer beyond the tonsillar herniation. Specifically, subgroups of patients, based on what
causes the herniation, are starting to emerge:
•
•
•
•
•
•
Small posterior fossa – some would call this classic Chiari, patients have distinctly smaller skull area
for the hindbrain. However, many aspects of this are still not clear and there are even some studies
that found this to not be the case.
CSF related – it is fairly well established that some patients with Chiari also have issues such as
hydrocephalus or intracranial hypertension. What is not clear is how these are linked to the
tonsillar herniation. Does the herniation lead to CSF issues or vice versa? Or are both an indication
of something else that is wrong. In addition, some people are found to have CSF issues after
decompression surgery. Did the surgery somehow cause this or was is simply undetected before
surgery?
Connective Tissue – it is also fairly well established that a subset of Chiari patients have some type
of EDS variant. While these patients may require additional treatment, such as cervical
fusion/stablilization, the precise link between an EDS variant and Chiari is less clear.
Tethered Cord – This is controversial and the research supporting it is limited and contradictory,
but some people believe that tethering at the base of the spinal cord, such as from a tight filum
terminale, can cause both tonsillar herniation and syrinxes.
Space occupying lesions – Perhaps the easiest to understand, a lesion or tumor in the brain which
takes up significant space can push the tonsils out of the skull.
Trauma? – The link between trauma and Chiari is not well understood at all. Does trauma spark
symptoms in people with classic Chiari anatomy? Can it actually cause herniation? Research into
this area is virtually non-existent.
It may turn out that the above groupings are incomplete, incorrect, or useless. Even if they are validated,
there are additional related questions, such as what role genetics plays, and why some people are born
with a small posterior fossa or CSF issues. Another way to encompass these questions is to say what is the
pathophysiology of Chiari, meaning simply, what causes Chiari?
3
Why are women affected more than men; is adult Chiari different than
pediatric Chiari?
Recently Conquer Chiari undertook a meta-analysis – a study of studies – to quantify the commonly
referred to gender discrepancy in Chiari. The analysis involved reviewing all published Chiari patient series
between 2008-2013 in which both the gender and age breakdown were clearly identified. Also, the patient
series had to be consecutive, meaning to be included it couldn’t be just patients with syringomyelia, or
some other selection criteria.
For pediatric patients (under the age of 18), 12 studies were found representing a total of 1793 patients. Of
those, the male/female split was almost even with 49.7% female and 50.3% male.
In contrast, for adult Chiari patients, 10 studies were found representing a similar number of patients
(1753), but the male to female ratio was dramatically different. Specifically, 70.5% were female, and only
29.5% were male.
So for Chiari among children, the split is almost exactly 50/50, but for adults, females are diagnosed more
than 2 to 1 compared to males.
This is a dramatic finding which raises two important questions. One, why are adult females affected more
often, and Two, why is the ratio different between pediatric and adult patients.
This area has not been researched, but understanding these differences could reveal some deep insights
into Chiari and would help to develop a comprehensive theory of Chiari.
4
What is the patient experience?
The launch of the Conquer Chiari Patient Registry was a big first step in answering this question.
Now that the registry has been up and running for a year, there should be sufficient data in it to address
this topic. With this in mind, Conquer Chiari recently issued a limited call for proposals to select research
teams to analyze the registry data and develop an innovative way to disseminate the information to the
patient community.
There are three main reasons why this is an important research question. One, characterizing the
epidemiological and natural history aspects of Chiari will establish a base line of understanding in terms of
the impact the disease has on patients (and families). For example, while surgeons may say a specific
decompression surgery was successful based on MRIs, this does not take into account whether that same
patient has had to change careers, drop out of school, made different decisions regarding family planning,
etc. The research community must determine the basics in order to measure any future progress.
Two, and no less important, is the fact that patients have a strong desire to know where they fit in. How
common are the symptoms they feel? Have other people had similar experiences with the medical
community? What have other tried for pain management? Conquer Chiari intends to use the data in the
registry to enable patients to do just that, compare themselves and their Chiari experience to others.
Three, is the very real possibility that by analyzing a large amount of data related to patients’ experiences,
clues will be found to further our understanding of Chiari. Why do some people respond better to
decompression surgery? Is there an ideal age to have surgery? What happens to people with moderate
symptoms who choose not to have surgery? This avenue of research will generate a myriad of further,
critically important, research questions to pursue.
5
What is the cognitive and emotional impact of Chiari?
One of the most insidious aspects of Chiari, but also one of the most poorly understood, is its effect
on a person’s cogni ve abili es and emo onal state. Unfortunately, the Conquer Chiari Pa ent Registry
indicates that a very high percentage of pa ents report cogni ve and emo onal issues. Poor recall,
difficulty planning, brain fog, anxiety, depression, and mood disorders seem to be all too common.
However, what is the actual link between Chiari and these problems? Do pa ents get depressed because of
poor experiences with the medical system and people telling them they are making things up? Or are these
issues a physical/chemical manifesta on of the tonsillar hernia on and raised intracranial pressure? Is it a
clue to a more fundamental understanding of Chiari?
As everyone who a ended the 2013 Open House is aware, the CCRC team is diving into this subject with
full force. They already have one publica on submi ed based on the research done at the open house and
have a series of research studies planned to shed more light on this cri cal ques on.
As it is studied scien cally, it is likely, but not guaranteed of course, that what is found will modify our
thinking about Chiari and lead to new insights and breakthroughs.
~Rick Labuda~
© 2003-2013 C&S Patient Education Foundation