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NEUROIMAGING IN TSC

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Neuroimaging (imaging of the brain) is one of the most important tools used in the diagnosis and management of tuberous sclerosis complex (TSC). Imaging in TSC usually involves computed tomography (CT) and/or magnetic resonance imaging (MRI) scans of the brain. Newer imaging techniques, such as positron emission tomography (PET) and magnetoencephalography (MEG), have been used for detecting specific changes in the brain.  The most common findings include cortical tubers, subependymal nodules, and subependymal giant cell tumors/astrocytomas.

After the diagnosis of TSC has been made, periodic follow-up scans may help identify areas of change or deterioration and/or for use in presurgical evaluation for individuals with intractable epilepsy. These techniques will be described in this Information Sheet, as well as their usefulness and limitations in individuals with TSC.

Computed Tomography

Computed Tomography (CT) scans produce a picture of the brain by directing a beam of X-rays through the targeted area at many different angles. A detector measures how much of the beam comes out on the other side. A computer then constructs a cross-sectional picture of the brain, based on many hundreds of readings from the detector. CT scans take less time to perform than MRIs. In fact, some machines can scan the brain in as little as 25 seconds. Nonetheless, it is important that a person hold as still as possible during the scan, so that the best possible pictures can be obtained.

CT scans can show tumors, but usually not as clearly as an MRI. However, calcification is seen better with CT than with MRI.  Build-up of fluid in or around the brain (hydrocephalus) can also be seen well on CT scans. Because they can be performed relatively quickly and are more easily available than MRIs, CT scans can help to exclude a major abnormality or dramatic change, such as tumor growth or hydrocephalus. When a person with TSC has a sudden change in behavior, increase in seizures or the abrupt onset of severe headaches, this can sometimes indicate that there has been such a change and may warrant the need for a scan.

Disadvantages of the CT include lower resolution (shows much less detail) than MRIs; the need for exposure to radiation (albeit at very small doses); and the need for sedation in individuals who cannot hold still. Also, adults rarely need sedation for a CT scan.

Magnetic Resonance Imaging (MRI)

MRIs involve placing a person in a tube inside a very strong magnet. MRIs provide a much more detailed picture of the brain. They can also be used to identify blood flow, chemical composition, flow of spinal fluid and blood vessels in various areas of the brain. They can identify tubers much better than CT scans, particularly when using a technique called FLAIR (fluid attenuated inversion recovery).

Contrast (dye) is usually given to help determine if a subependymal nodule is beginning to grow into a subependymal giant cell tumor/astrocytoma. An MRI is better able to assess any changes in tubers, tumors, or subependymal nodules that can occur over time. An MRI scan does take much longer to per-form than a CT scan – as long as 45 minutes to an hour. Some special scans may take even longer.

The MRI scans are also more expensive. The space in the magnet for the person being scanned is rather small, and some people may get claustrophobic. So-called “open” MRIs have magnets that are open on the sides, and are less confining. However, their image quality is poor, and they are not desirable for use for individuals with TSC.

It is very important to hold perfectly still during an MRI, as the pictures are easily distorted by movement. Most children and many adults will require sedation. An advantage is that an MRI does not require exposure to radiation. This can be important since many people with TSC need to have several brain scans over a lifetime. In fact, some centers do brain scans as often as every year until puberty.

Magnetic Resonance Angiography

Magnetic resonance angiography (MRA) is a screening tool used to look for problems in the blood vessels in the brain.  Cerebro-vascular occlusive disease and vascular ectasias or aneurysm are sometimes identified in individuals with TSC.  What makes these findings unique in TSC is that they are identified in individuals with TSC at much younger ages (teens and early 20s) than in the general population. 

Fetal MRI

MRI may play a prominent role in the evaluation of pregnancies at risk for TSC (Curatolo and Brinchi, 1993).  The brain lesions in TSC can be seen as early as 26 weeks gestation.  If a fetus has cardiac rhabdomyomas observed using fetal ultrasonography and the concomitant presence of both subependymal nodules and cortical tubers, a definitive diagnosis of TSC can be made.

Positron Emission Tomography

Positron emission tomography (PET) is a non-invasive imaging tool that measures the regional uptake and use of substances by the brain and other organs.  For the brain, PET has been used to identify the specific area causing epileptic seizures in the pre-surgery evaluation, and also to study cognitive aspects of various disease conditions, including TSC.  PET has been used to detect cortical tubers in TSC since 1983 (Szelies et al., 1983), and newer PET methods are beginning to play an important role in the presurgical evaluation of individuals with TSC with refractory epilepsy.  Use of PET scanning with 2-deoxy-2-[¹⁸F]fluoro-D-glucose (FDG) clearly demonstrates cortical tubers as regions with 30-60% lower glucose metabolic rate than in the same region on the other side of the brain (Szelies et al., 1983).  Thus, FDG PET has two major roles in epilepsy surgery for TSC: 1) to detect cortical tubers as well as surrounding dysplastic (abnormal) areas with high sensitivity; and 2) to assess the full extent of functional abnormality in the opposite side of the brain, thereby predicting the possible impact of surgery on cognition.

A newer tool, a-[¹¹C]methyl-L-tryptophan (AMT) PET, is being used to identify the specific area of the brain where the seizures begin.  AMT showed 20-188% higher uptake in epileptogenic compared to non-epileptogenic tubers in two-thirds of the individuals with TSC with medically intractable epilepsy (Chugani et al., 1998; Asano et al., 2000). AMT PET is now used as one tool in the presurgical evaluation of individuals with TSC for epilepsy surgery (Kagawa et al., 2005).

Magnetoencephalography

An improvement in functional localization can be obtained by combining electroencephalogram (EEG) and magnetoencephalography (MEG) signals.  MEG measures magnetic fields that are primarily associated with intracranial (brain) currents.  The intracranial currents that pass into the skull and scalp and are picked up by an EEG are only about 5% of the currents.  Therefore, MEG is better able to pick up the currents in the brain and can better localize the source of the seizures.

Magnetic source imaging (MSI) combines MEG data on brain function with MRI data on brain structure.  MSI allows for more accurate localization of the area that is abnormal and the source of the seizures.  It remains unclear to what extent MSI will be of assistance in avoiding invasive studies in surgery candidates and in helping the neurosurgeon to perform individualized and conservative brain resection in individuals with intractable localization-related seizures associated with TSC.  However, recent studies show promising results utilizing MSI for individuals with TSC (Persson et al., 1998; Iida et al., 2005; Janssen et al., 2006; Wu et al., 2006).

Sedation

Many people will need to be sedated for one or both of these imaging techniques. It is critical that sedation be performed safely and by experienced personnel, but also that it be sufficient for the individual to remain asleep throughout the entire procedure. Taking mild sedatives prescribed by a family doctor are almost always inadequate. In fact, many people become more anxious or agitated when they receive such a medicine. Since CT scans without contrast can be done so quickly, sedation is often not necessary. Scheduling a scan when a child is already sleepy or just after an infant has been fed (“milk sedation”) can be very useful.

For MRI scans, infants and young children are often sedated with an oral medicine. Nembutal may be used to sedate children, although some facilities use a drug called chloral hydrate. Older children usually need intravenous sedation. Certain people may require an anesthesiologist to be safely and adequately sedated. Whichever technique is used, it is important to be sure that the staff at the scanning facility are thoroughly trained and able to handle any problems that may arise. This is particularly true for infants and children and for severely affected adults with TSC.  The risk of complication from sedation for these imaging tests is far less than 0.1%.

References

Asano E, Chugani DC, Muzik O, et al. (2000) Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex.  Neurology  54:1976-84

Chugani DC, Chugani HT, Muzik O, et al. (1998) Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[C-11]methyl-L-tryptophan positron emission tomography.  Ann Neurol  44:858-66

Curatolo P, Brinchi V (1993) Antenatal diagnosis of tuberous sclerosis.  Lancet 341:176-7

Iida K, Otsubo H, Mohamed IS, Okuda C, Ochi A, Weiss SK, Chuang SH, Snead OC 3rd (2005) Characterizing magnetoencephalographic spike sources in children with tuberous sclerosis complex. Epilepsia 46(9):1510-7

Jansen FE, Huiskamp G, van Huffelen AC, Bourez-Swart M, Boere E, Gebbink T, Vincken KL, van Nieuwenhuizen O (2006) Identification of the epileptogenic tuber in patients with tuberous sclerosis: a comparison of high-resolution EEG and MEG. Epilepsia 47(1):108-14

Kagawa K, Chugani DC, Asano E, Juhasz C, Muzik O, Shah A, Shah J, Sood S, Kupsky WJ, Mangner TJ, Chakraborty PK, Chugani HT. Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET). J Child Neurol. 2005; 20(5):429-38.

Peresson M, Lopez L, Marici L, Curatolo P (1998) Magnetic source imaging and reactivity to rhythmical stimulation in tuberous sclerosis. Brain Dev 20(7):512-8

Szelies B, Herholz K, Heiss WD, et al. (1983) Hypometabolic cortical lesions in tuberous sclerosis with epilepsy: demonstration by positron emission tomography. J Comput Assist Tomogr 7:946-53

Wu JY, Sutherling WW, Koh S, Salamon N, Jonas R, Yudovin S, Sankar R, Shields WD, Mathern GW (2006) Magnetic source imaging localizes epileptogenic zone in children with tuberous sclerosis complex. Neurology 66(8):1270-2

By David Neal Franz, M.D., Professor of Pediatrics and Neurology and Director of the Tuberous Sclerosis Clinic, and John C. Egelhoff, D.O., Professor of Radiology and Pediatrics, both at the University of Cincinnati College of Medicine, Children’s Hospital Medical Center in Cincinnati, Ohio.

** Tuberous Sclerosis Alliance Information Sheets are intended to provide basic information about TSC. They are not intended to, nor do they, constitute medical or other advice. Readers are warned not to take any action with regard to medical treatment without first consulting a physician.  The TS Alliance does not promote or recommend any treatment, therapy, institution or health care plan. 

Made possible through an educational grant from the Schnurmacher Foundations.  June 2006