Synonyms of Chiari Malformations
- Arnold-Chiari Malformation (ACM)
- Hindbrain Herniation
- Tonsillar Ectopia
- Chiari type 0 (Chiari malformation 0)
- Chiari type I (Chiari malformation I)
- Chiari type II (Chiari malformation II)
- Chiari type III (Chiari malformation III)
- Chiari type IV (Chiari malformation IV)
Chiari malformations are a group of complex brain abnormalities that affect the area in lower posterior skull where the brain and spinal cord connect. The underlying anatomy of Chiari malformations is thought to be present at birth (congenital), although in many cases they may not become clinically apparent until adulthood. In extremely rare cases, a Chiari malformation may be acquired during life. The exact cause of Chiari malformations are not known, but often the cavity near the base of the skull (posterior fossa) is narrow and abnormally small in relation to the size of the cerebellum, which this portion of the skull encloses. Researchers believe that in some cases the small posterior fossa may cause the developing brain, specifically the cerebellum and the brainstem, to be pushed downward. Part of the cerebellum (known as the cerebellar tonsils) may protrude (herniate) through the foramen magnum, which is the normal opening found in the occipital bone at the base of the skull. The tonsils may thus interfere with the flow of cerebrospinal fluid (CSF) to and from the skull and spinal canal, potentially leading to accumulation of cerebral spinal fluid in the subarachnoid spaces of the brain and spine. A Chiari malformation can also cause pressure on the brain and produce hydrocephalus (pressure due to excessive cerebrospinal fluid accumulation in the brain) and the spinal cord, potentially causing a wide variety of symptoms. In fact, no two cases of Chiari malformation are exactly alike and the associated symptoms are highly variable. The severity of Chiari malformations can vary dramatically as well. In some cases, affected individuals may not develop any symptoms (asymptomatic); in others, severe, potentially debilitating or life-threatening symptoms can develop.
Traditionally, Chiari malformations have been defined and classified by how much of the cerebellar tonsils protrude through the foramen magnum. A diagnosis of a Chiari malformation usually signifies that the cerebellar tonsils protrude below the foramen magnum (often cited as at least 5 millimeters, though this is controversial). However, researchers have determined that the length of tonsil descent in a Chiari malformation does not always correspond to the severity of symptoms or to the response to treatment. In fact, some individuals are classified as having Chiari malformation type 0, in which there is minimal or no descent of the cerebellar tonsils. These individuals still have symptoms associated with a Chiari malformation, most likely due to abnormalities in the flow of cerebrospinal fluid within the skull and spinal canal. Research is ongoing to understand the complex, underlying mechanisms that cause Chiari malformations.
Chiari malformations are named for Hans Chiari, an Austrian pathologist, who first identified type I-III in 1891. Julius Arnold further expanded the definition of Chiari malformation type II and some medical sources began using the name Arnold-Chiari malformation. Nowadays, some medical sources use Arnold-Chiari malformation as a broad term for all forms. Chiari malformations have also been known as congenital tonsillar herniation, tonsillar ectopia or tonsillar descent.
The signs and symptoms of Chiari malformation can vary greatly from one person to another. Some individuals may not have any symptoms (asymptomatic) upon diagnosis as an incidental finding; others may have serious manifestations such as neurological deficits. Symptoms may go through periods of exacerbation and remission. Chiari malformations are highly variable conditions that will affect every individual person differently. Specific symptoms can occur in different combinations and generally reflect dysfunction of the cerebellum, the brainstem, the spinal cord and lower cranial nerves. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
The most common symptom associated with a Chiari malformation is occipital headaches. These headaches are felt near the base of the skull and may radiate to cause pain in the neck and shoulders. They can be severe and may be described as sharp, brief, throbbing or pulsating. Occipital headaches can be brought on or worsened by coughing, straining or sneezing.
Abnormalities affecting the eyes can also affect individuals with a Chiari malformation including double vision (diplopia), abnormal sensitivity to light (photophobia), blurred vision, involuntary eye movements (nystagmus) and pain behind the eyes. Vertigo, dizziness, ringing in the ears (tinnitus) and bilateral hearing impairment can also develop.
Additional symptoms associated with a Chiari malformation may include poor coordination and balance problems, muscle weakness, difficulties swallowing (dysphagia) or speaking (dysarthria), palpitations, fainting episodes (syncope) and tingling or burning sensations in the fingers, toes or lips (paresthesias). Sleep disorders, especially sleep apnea and chronic fatigue, have also been described in individuals with Chiari malformations.
Affected individuals may also develop a fluid-filled cavity or cyst in the spinal cord (syrinx), a condition known as syringomyelia. This condition is chronic and a syrinx can expand over time. Syringomyelia can be associated with a variety of symptoms depending upon the size and specific location of the syrinx. Potential symptoms include loss of muscle mass, muscle weakness, numbness or decreased sensation especially to hot and cold, abnormal curvature of the spine (scoliosis), loss of bowel and bladder control, chronic pain, muscle contractions, uncoordinated movements (ataxia), and spasms and tightening of the muscles of the legs (spasticity).
Some individuals have a condition related to syringomyelia known as hydromyelia, which is characterized by abnormal widening of the central canal of the spinal cord (the small canal running through the center of the spinal cord). These small cavities are filled with cerebrospinal fluid and their significance, if any, is not known. Some physicians use the terms syringomyelia or hydromyelia interchangeably. However, hydromyelia cavities connect to the fourth ventricle (an area in the brain that normally contains cerebrospinal fluid). Hydromyelia may also be present in infants and young children with or without brain abnormalities, such as Chiari malformation type II. The fluid-filled cavities in cases of syringomyelia often do not connect to any other fluid-filled areas or spaces and occur more often in adults than children.
CHIARI MALFORMATION TYPE I
Chiari malformation type I is the most common cause of syringomyelia. It may not cause any symptoms and often goes unrecognized until adolescence or adulthood. Consequently, this form is sometimes referred to as adult Chiari malformation. Chiari malformation type I is usually not associated with other neurological abnormalities, although it can cause neurological symptoms due to compression of the brainstem and spinal cord.
CHIARI MALFORMATION TYPE II
Chiari malformation type II is usually more severe than type I and generally symptoms become apparent during childhood. The severity of Chiari malformation type II can vary greatly. The disorder can potentially cause severe, life-threatening complications during infancy or childhood.
In Chiari malformation type II, cerebellar tissue protrudes all the way into the spinal canal. Affected individuals may have some of the symptoms described above. However, additional findings such as hydrocephalus may also occur. Hydrocephalus is a condition in which accumulation of excessive cerebrospinal fluid in the brain ventricles causes pressure on the tissues of the brain. Hydrocephalus can cause an abnormally enlarged head (macrocephaly), vomiting, irritability, seizures, and delays in attaining developmental milestones. The specific symptoms associated with hydrocephalus can vary from one child to another.
Chiari malformation type II is almost invariably associated with a form of spina bifida, frequently presenting as myelomeningocele. Spina bifida is a birth defect due to incomplete closure of the posterior spinal cord and bony vertebral arch (lamina). Many cases with this anomaly leave a portion of the spinal cord exposed through the spinal canal, typically forming a sac filled with cerebrospinal fluid, meninges, and portions of the spinal cord and nerves (myelomeningocele). Myelomeningocele can be associated with partial or complete paralysis below the spinal opening, including lack of bladder and bowel control.
Chiari malformation type II can be associated with other significant neurological conditions including complex anomalies of the brain. Chiari malformation type II is sometimes referred to as pediatric Chiari malformation and requires surgical intervention during infancy or early childhood.
CHIARI MALFORMATION TYPE III
Chiari malformation type III is extremely rare and more severe than Chiari malformations types I and II. This form is associated with an encephalocele, a condition in which a portion of the brain and its surrounding membranes (meninges) protrude through a defect in the skull.
Affected individuals have many of the symptoms associated with Chiari malformation type II, but also have additional symptoms. Chiari malformation type III is often associated with debilitating and life-threatening complications in infancy.
CHIARI MALFORMATION TYPE IV
Unlike types I-III, Chiari malformation type IV is not associated with herniation of the brain through the foramen magnum. In this condition, the brain is underdeveloped (hypoplastic) or fails to develop (aplastic). Chiari malformation type IV is the most severe form and is usually fatal during infancy. Because of the lack of cerebellar tonsillar herniation, some researchers do not consider this condition a form of Chiari malformation.
CHIARI MALFORMATION TYPE 0
Researchers have determined that some individuals with a Chiari malformation have minimal or no herniation of the cerebellar tonsils through the foramen magnum. These individuals often have syringomyelia despite the lack of cerebellar tonsil herniation. Occipital headaches may also occur. Symptoms in these cases are most likely due to abnormalities in the flow of cerebrospinal fluid at the level of the foramen magnum at the skull base, although there is often no identifiable cause. Individuals with this condition have improved after decompression surgery. The addition of Chiari malformation type 0 as a classification for Chiari malformations is controversial; some physicians believe that, for a diagnosis of a Chiari malformation, tonsillar herniation must be present.
The exact cause of Chiari malformations is unknown. These malformations and the associated central nervous system abnormalities are extremely complex. Chiari malformations appear to be due to a developmental failure of the brainstem and upper spinal cord (cervical region) within a developing fetus with no known cause. Some investigators believe that an abnormally small posterior fossa, which is the space in which the cerebellum normally resides, contributes to the development of a Chiari malformation. In many individuals, the posterior fossa is abnormally small, which may lead to the growing brain being pushed down through the normal opening (foramen magnum) where the brain and spinal cord meet.
The specific parts of the cerebellum that are affected are the cerebellar tonsils. The cerebellum is the part of the brain that plays a role in maintaining balance and posture as well as coordinating voluntary movements. The cerebellar tonsils are small peg-like structures at the base of the cerebellum. When the tonsils protrude through the foramen magnum, they block the proper flow of cerebrospinal fluid between the skull and the spinal cord, potentially compressing the brainstem (pons medulla) and the upper portion of the spinal cord.
There have been numerous reports in the medical literature of families in which more than one family member was affected by a Chiari malformation. This suggests that in some cases genetic factors play a role in the development of a Chiari malformation. Research is ongoing to determine the specific genetic components (e.g., gene mutations) that influence the development of Chiari malformations in some people.
In extremely rare cases, Chiari malformations have been acquired during life. Generally, any condition that takes up space within the skull, especially within the posterior fossa of the skull, can cause an acquired Chiari malformation. Such conditions include tumors, an arachnoid cyst, and hematomas. Hydrocephalus and intracranial hypertension (pseudotumor cerebri) have also been linked to Chiari malformations. Abnormalities that affect the upper cervical portion of the spine, such as basilar invagination, can also cause a Chiari malformation. Basilar invagination occurs when the upper vertebrae are located upward, blocking the foramen magnum and thereby blocking the flow of cerebrospinal fluid.
Leakage or drainage of CSF including the prolonged use of a lumboperitoneal shunt, which is often used to treat hydrocephalus, has been linked to the development of an acquired Chiari malformation. One theory states that if too much cerebrospinal fluid is drained, it might create a pressure imbalance between the cranial and spinal fluid compartments. Consequently, this pressure imbalance is theorized to suck or draw the cerebellar tonsils downward through the foramen magnum.
Some researchers have speculated that, in a specific subset of individuals, a Chiari malformation may be caused by a tethered cord. Such individuals have a normal-sized posterior fossa. Tethered cord syndrome is a stretch-induced functional disorder associated with the fixation (tethering) effect of inelastic tissue (filum terminale) on the lower end of the spinal cord, limiting its normal upward movement. This abnormal attachment is associated with progressive stretching and increased tension of the spinal cord as a child grows, potentially resulting in a variety of neurological and other symptoms. While some individuals have both a tethered cord and a Chiari malformation, the exact relationship between these two disorders is not understood. Whether tethered cord syndrome is a distinct cause of Chiari malformations in certain cases is unproven and controversial.
Chiari malformations can also occur as part of a larger syndrome such as Goldenhar syndrome, Albright hereditary osteodystrophy (pseudohypoparathyroidism), Hajdu-Cheney syndrome, achondroplasia and hereditary connective tissue diseases such as Ehlers-Danlos syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
Many of the symptoms of a Chiari malformation are believed to be due to abnormalities affecting the flow of cerebrospinal fluid (CSF) in the skull and spinal canal. Syringomyelia, which is often associated with a Chiari malformation, most likely develops due to partial obstruction of the normal flow of CSF between the brain and spinal cord. Some symptoms associated with a Chiari malformation or syringomyelia result from direct compression of portions of the brainstem or spinal cord. Researchers have determined that the length of herniation (i.e., the amount of the cerebellar tonsils that protrudes through the foramen magnum) does not necessarily correspond to the severity of a Chiari malformation.
Chiari malformations affect individuals of every race and ethnicity. Some studies suggest that females are affected more often than males. In most cases, a Chiari malformation is thought to be present at birth (congenital), although some cases may not be discovered until adulthood (sometimes incidentally when a brain scan is done for another reason). The incidence and prevalence of Chiari malformations are unknown. Some cases may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of these disorders in the general population.
Symptoms of the following disorders can be similar to those of Chiari malformation. Comparisons may be useful for a differential diagnosis.
There are a wide variety of conditions that can be considered in the differential diagnosis of a Chiari malformation. The symptoms commonly associated with a Chiari malformation are vague and common to numerous other conditions. Some disorders are common misdiagnoses for individuals with a Chiari malformation. Such conditions include multiple sclerosis, chronic fatigue syndrome, fibromyalgia and spinal cord tumors. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
A diagnosis of a Chiari malformation is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a neurological exam that includes a variety of specialized tests including specialized imaging techniques.
Clinical Testing and Work-Up
Imaging techniques may include magnetic resonance imaging (MRI), cine MRI and plain X-rays. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. An MRI can reveal excess CSF and loss of neural tissue. A cine MRI is like a traditional MRI, but can be used to measure and assess CSF flow. Interpreting a cine MRI is difficult and the procedure is best at diagnosing obvious CSF flow abnormalities (as opposed to borderline cases). Consequently, not all physicians advocate its use.
A plain X-ray can reveal skeletal malformations such as skull defects, abnormalities of cervical vertebrae or abnormal curvature or abnormal motion of the spine. Computed tomography (CT) scans may be helpful in clarifying congenital bony abnormalities at the skull base. Additional tests may be performed to detect or assess other complications potentially associated with a Chiari malformation. Such tests may include a swallowing test to assess how well someone can drink fluids or swallow thickened food and sleep studies to detect sleep disorders potentially associated with Chiari malformations.
The treatment of a Chiari malformation is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurosurgeons, neurologists, eye specialists (ophthalmologists) and other healthcare professionals may need to systematically and comprehensively plan a patient's treatment.
Treatment procedures and interventions may vary, depending upon numerous factors, such as disease progression; the presence or absence of certain symptoms; the relationship of the malformation to the main physical symptoms; the impact of symptoms on overall quality of life; an individual's age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient and should be based upon the specifics of his or her case, a thorough discussion of the potential benefits and risks including possible side effects and long-term effects, patient preference, and other appropriate factors.
Neurosurgeons and other physicians may disagree as to the best approach to treat a Chiari malformation. There is no specific, agreed-upon therapy or treatment regimen. Different neurosurgeons may recommend different surgical techniques or treatment regimens.
Generally, individuals with no symptoms are not treated, but are regularly monitored to see whether the disorder progresses. If mild symptoms are present such as neck pain or headaches, physicians may recommend conservative treatment such as pain medications, massage therapy or a reduction in activities, particularly those involving heavy lifting or straining. Physical therapy may be tried in some cases, but some physicians argue against its use stating that physical therapy for individuals with a Chiari malformation is not always effective.
Symptomatic Chiari malformations are most often treated by surgery. There are no specific criteria or objective tests that can be used to determine when to undergo surgery or the best procedures to choose. The procedure that is best may differ for children and adults. The most common surgery is known as posterior fossa decompression. With this procedure, a surgeon creates room by removing small pieces of bone in the back of the skull, thereby enlarging the foramen magnum. This relieves pressure and reduces compression on the brainstem, and may allow the cerebellar tonsils to move back to a more normal position.
There are usually a few steps during the surgical decompression of the posterior fossa including,
Removal of a piece of the skull (craniectomy). This can relieve pressure and give more room for cerebrospinal fluid circulation. A craniectomy may be enough in some cases of mild tonsillar descent. However, many cases require the additional procedures described below.
Removal of part of the bony covering of the spinal canal (laminectomy) in order to provide more room for cerebrospinal fluid circulation and to remove scar tissue. In most instances, the laminectomy is limited to C1, the first cervical vertebra.
Cutting open of the tough outer membrane covering the brain and spinal cord (dura) and sewing in a patch to make it bigger (duraplasty). The patch used in a duraplasty may be made from artificial material or from tissue harvested from another area of the body. A duraplasty is performed to provide even more room for decompression, although some physicians argue against the necessity of this step. It may not be necessary in children.
Shrinking of the cerebellar tonsils. Some neurosurgeons advocate cauterizing (applying a small amount of electricity) to the cerebellar tonsils, which causes tonsillar tissue to shrink and retract. This is more invasive and is not advocated by all neurosurgeons, but appears necessary for at least some patients.
Insertion of an artificial plate over the area where the skull was removed.
Surgical treatment of a Chiari malformation has variable results. One study found that more than 80 percent of adults reported significant improvement in symptoms after surgery. However, response to therapy is highly variable. Symptoms related to a Chiari malformation may respond differently from symptoms related to an associated syringomyelia. Although some individuals experience significant improvement, others may have symptoms that persist including residual pain, muscle weakness, and loss of sensation. In addition, surgery carries risks such as leakage of cerebrospinal fluid or infection.
Individuals with hydrocephalus may be treated by the implantation of a tube (shunt) to drain excessive cerebrospinal fluid away from the skull and brain to another part of the body where the CSF can be absorbed. In some cases, shunts may relieve CSF pressure and improve symptoms. In other cases, individuals require surgical intervention as described above. Before surgery can be performed, the excessive fluid may need to be drained via shunt insertion.
A myelomeningocele, which is usually associated with Chiari malformation type II, requires surgical repair.
Syringomyelia associated with a Chiari malformation usually does not require direct treatment. In most cases, syringomyelia improves on its own after surgery to correct a Chiari malformation because the normal flow of cerebrospinal fluid is restored.
An acquired Chiari malformation requires treatment of the underlying condition. In many cases, a Chiari malformation may resolve without further treatment in such cases.
Genetic counseling may be of benefit for affected individuals and their families. Additional treatment is symptomatic and supportive.
Individuals require periodic follow up after surgical treatment for a Chiari malformation. Symptoms may recur after a successful surgery, usually within the first two years. Most likely, this is due to the development of scar tissue or an opening around the duraplasty covering the brain. Children required periodic MRI examinations because of the normal continued growth of the brain and skull.
IInformation on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, in the main, contact:
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Organizations related to Chiari Malformations
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
Milhorat TM, Nishikawa M, Kula RW, Dlugacz YD. Mechanisms of cerebellar tonsil herniation in patients with Chiari malformations as a guide to clinical management. Acta Neurochir. 2010;152:1117-1127. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887504/?tool=pubmed
Mutchnick IS, Janjua RM, Moeller K, Moriarty TM. Decompression of Chiari malformation with and without duraplasty: morbidity versus recurrence. J Neurosurg Pediatrics. 2010;5:474-478. http://www.ncbi.nlm.nih.gov/pubmed/20433261
Galarza M, Lopez-Guerrero AL, Martinez-Lage JF. Posterior fossa arachnoid cysts and cerebellar tonsillar descent: short review. Neurosurg Rev. 2010;33:305-314. http://www.ncbi.nlm.nih.gov/pubmed/20480382
Aghakhani N, Parker F, David P, et al. Long-term follow-up of Chiari-related syringomyelia in adults: analysis of 157 surgically treated cases. Neurosurgery. 2009;64:308-315. http://www.ncbi.nlm.nih.gov/pubmed/19190458
Fernandez AA, Guerrero AI, Martinez MI, et al. Malformations of the craniocervical junction (Chiari type I and syringomyelia: classification, diagnosis and treatment. BMC Musculoskelet Disord. 2009;10 Suppl 1:S1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796052/
Attenello FJ, McGirt MJ, Gathinji M, et al. Outcome of Chiari-associated syringomyelia after hindbrain decompression in children: analysis of 49 consecutive cases. Neurosurgery. 2008;62:1307-1313. http://www.ncbi.nlm.nih.gov/pubmed/18824997
Dauvilliers Y, Stal V, Abril B, et al. Chiari malformations and sleep related breathing disorders. J Neurol Neurosurg Psychiatry. 2007;78:1344-1348. http://www.ncbi.nlm.nih.gov/pubmed/17400590
Szewka AJ, Walsh LE, Boaz JC, Carvalho KS, Golomb MR. Chiari in the family: inheritance of the Chiari I malformation. Pediatr Neurol. 2006;34:481-485. http://www.ncbi.nlm.nih.gov/pubmed/16765829
Stevenson KL. Chiari Type II malformation: past, present and future. Neurosurg Focus. 2004;16:1-7. http://thejns.org/doi/pdf/10.3171/foc.2004.16.2.6
Greenlee JDW, Donovan KA, Hasan DM, Menezes AH. Chiari I malformation in the very young child: the spectrum of presentations and experience in 31 children under age 6 years. Pediatrics. 2002;110:1212-1219. http://pediatrics.aappublications.org/content/110/6/1212.full.pdf
Milhorat TH, Chou MW, Trinidad EM, et al. Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery. 1999;44:1005-1017. http://www.ncbi.nlm.nih.gov/pubmed/10232534
Pakzaban P. Chiari Malformation. Emedicine Journal, Updated: Feb 4, 2014. Available at: http://emedicine.medscape.com/article/1483583-overview Accessed March 5, 2014.
National Institute of Neurological Disorders and Stoke. Chiari Malformation Fact Sheet. Last updated December 30, 2013. Available at: http://www.ninds.nih.gov/disorders/chiari/detail_chiari.htm Accessed March 5, 2014.
Batzdorf U, Benzel EC, Ellenbogen RG, et al. American Syringomyelia & Chiari Alliance Project. Chiari malformation and syringomyelia. A handbook for patients and their families. 2008. Available at: http://www.asap.org/handbook.pdf Accessed March 5, 2014.
Mayo Clinic for Medical Education and Research. Chiari Malformation. Aug. 21, 2013. Available at: http://www.mayoclinic.com/health/chiari-malformation/DS00839 Accessed March 5, 2014.
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