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EPILEPSY SURGERY FOR INDIVIDUALS WITH TSC

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Seizures are common manifestations of tuberous sclerosis complex (TSC). It is estimated that as many as 80 to 90 percent of individuals with TSC will have seizure(s), often beginning in childhood.  Several new antiepileptic drugs (seizure medications) have become available in recent years, and these drugs along with the older medications control the seizures for many individuals. Unfortunately, for some individuals with TSC, the seizure activity proves “intractable” to medication. This means that despite good trials of appropriate medications, the individual continues to have seizures, so other therapeutic options should be considered. Currently, these options include: the ketogenic diet, the vagal nerve stimulator (VNS), epilepsy surgery and clinical trials.

With regard to the surgical options, different procedures can be effective depending on the type of seizures.  The Corpus Callosotomy (CC) is a procedure that “splits the brain” by dividing the corpus callosum, a structure that connects the right and left hemispheres, or halves, of the brain.  Another type of epilepsy surgery called respective surgery involves removal of the area(s) of the brain that is/are causing seizures.

The Ideal Surgical Candidate

Several reports in medical literature suggest that epilepsy surgery can be a successful treatment for individuals with TSC. This has been and still is debated, primarily because individuals with TSC typically have more than one area of abnormal brain area, or tuber, and more than one seizure focus (area of the brain causing the seizures).  The “ideal” candidate for resective surgery is a person with one seizure type and a clear correlation with one specific seizure focus in an area of the brain that can be safely removed without causing a significant loss of function. When a person has multiple seizure types (particularly “drop seizures”) that cannot be clearly localized (that is identified as coming from a single tuber or from a specific region of the brain), then a CC may be the more appropriate surgical procedure.  Of course, this will vary from one individual with TSC to the next, so careful evaluations and planning by an experienced group of health care providers are critical to the process.
 
Since individuals with TSC usually have multiple tubers and multiple seizure types, they have not been considered “ideal” surgical candidates. One concern is that it is not possible to predict which tubers, if any may, cause seizures in the future. However, if the seizures are significantly impacting the individual’s life, the possibility of surgery should be considered.  Recent experience suggests that some individuals with difficult to localize seizures or with multiple seizure foci may still benefit from removal of one or more of the seizure-producing areas. It is only after a multi-phased workup that the appropriate surgical procedure (if any) can be determined. Therefore, multiple tubers/seizure foci are not necessarily a contraindication for resective surgery.

Phase I (Presurgical Evaluation)

If surgery is to be considered, individuals should be evaluated at a center with a well-established comprehensive epilepsy program that includes epilepsy surgery.  A pre-surgical or Phase 1 evaluation is performed in order to determine if an individual with TSC is a surgical candidate. This consists of a hospitalization on an epilepsy-monitoring unit (EMU) to record the seizure(s) with continuous video EEG monitoring. It is during this initial phase that the seizures are identified and the specific area where the seizures are starting (seizure onset) is tentatively localized (if possible).

In addition to the video EEG to define the seizures, other evaluations may also be performed. Neuropsychological or developmental assessments are used to help establish a person’s functional strengths and weaknesses. These may also help localize the seizure focus. Imaging studies, particularly an MRI defines the “structural abnormalities” (tubers). Depending on the institution, other structural as well as functional imaging studies may include: positron emission tomography (PET) single photon emission tomography (SPECT), magnetoencephalography (MEG), Diffusion Tensor Imaging (DTI) and functional MRI (firm). Finally, a Wada test  may also be performed. This is done by doing an angiogram  in order to put one hemisphere of the brain “to sleep” at a time. The neuropsychologist then does behavioral testing to identify in which hemisphere language and memory function are located.

All study results are used to determine which individuals may proceed to the next phase.  Once again, the individuals that may be the best candidates for resective surgery will be those who have a clear focal onset of their seizure from an area with a tuber that is not in an important functional area of the brain. However, even when someone may not be the “ideal” candidate, the information from phase I may still suggest that a surgical option is possible and that they may proceed to Phase II.

In some cases it may be decided after Phase I that a resection is not possible. This may be because a single, dominant focus cannot be identified or that it could not be safely removed based on its location or proximity to important brain function. If this happens, other options may be considered, including a CC. This is an option in very specific situations, in particular if the person has Lennox-Gastaut Syndrome with drop seizures or has frequent episodes of prolonged seizures (status epilepticus).  On rare occasions, following a CC, the seizures may change and suggest a focal onset so that it becomes feasible to consider a resection and proceed to Phase II.  

Phase II (Resective Surgery)

Following the Phase 1 evaluation, the epilepsy surgery team, which includes the neurologist and/or epileptologist , neurosurgeon, neuroradiologists and neuropsychologists, reviews all collected data and decides if epilepsy surgery would likely lead to a significant reduction in seizures without causing a loss of important function (i.e. speech, use of a hand, etc.). This evaluation frequently identifies the tuber or tubers thought to be involved in the individual’s epilepsy that could be safely removed.

In many cases, particularly for individuals with TSC and multiple tubers, further monitoring is necessary to better delineate the epileptogenic region(s). This involves invasive monitoring with subdural electrodes, rather than a scalp EEG. This means the individual has surgery to place special electrodes on the surface of the brain for video EEG monitoring once again.  This recording produces a “map” of the seizure focus.  These same electrodes are also used for making a “functional map.” This is done by using a small electrical current to directly stimulate the surface of the brain to identify the functional area that is monitored by the electrodes (i.e. speech, hand movement, etc.). The map of the seizure focus and the functional map are then combined into a single map. If the seizure focus does not overlap with any important function it may then be removed and hopefully result in good seizure control. If the seizure focus and important function do overlap, complete removal of the tuber may not be possible.

There may also be situations when it is necessary and safe to record and map the seizure focus and function in both hemispheres to remove bilateral (on both sides of the brain) seizure foci (and tubers). This approach is even more complicated than a resection in one hemisphere and therefore is less commonly performed.

The time needed to complete phase II (the mapping and resection) varies depending on how long it takes to record enough seizures and finish the functional map.
 
Conclusion

Seizures are extremely common in individuals with TSC. They may be frequent and severe enough in spite of treatment with multiple medications to consider other therapeutic options, including epilepsy surgery. This is a complicated process to achieve the desired outcome of seizure control (with or without the continued need for anticonvulsant medications). Therefore it is best to go to a comprehensive epilepsy center.

Remember, the goal of any treatment for seizures is complete seizure control with minimal or no side effects to the treatment. It is appropriate to pursue all reasonable means to achieve this goal, including epilepsy surgery.

References

Asano E, Juhasz C, Shah A, Muzik O, Chugani DC, Shah J, Sood S, Chugani HT (2005) Origin and propagation of epileptic spasms delineated on electrocorticography. Epilepsia 46(7):1086-97

Jansen FE, Braun KP, van Nieuwenhuizen O, Huiskamp G, Vincken KL, van Huffelen AC, van der Grond J (2003) Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis.  Arch Neurol 60(11):1580-4

Jarrar RG, Buchhalter JR, Raffel C (2004) Long-term outcome of epilepsy surgery in patients with tuberous sclerosis. Neurology 62(3):479-81

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

Kawai K, Shimizu H, Yagishita A, Maehara T, Tamagawa K (2004) Clinical outcomes after corpus callosotomy in patients with bihemispheric malformations of cortical development. J Neurosurg 101(1 Suppl):7-15

Lachhwani DK, Pestana E, Gupta A, Kotagal P, Bingaman W, Wyllie E (2005)
Identification of candidates for epilepsy surgery in patients with tuberous sclerosis. Neurology 64(9):1651-4

Romanelli P, Najjar S, Weiner HL, Devinsky O (2002) Epilepsy surgery in tuberous sclerosis: multistage procedures with bilateral or multilobar foci. J Child Neurol 17(9):689-92

Shields WD (2004) Surgical Treatment of Refractory Epilepsy. Curr Treat Options Neurol 6(5):349-356

Thiele EA (2004) Managing epilepsy in tuberous sclerosis complex. J Child Neurol 19(9):680-6

Weiner HL, Ferraris N, LaJoie J, Miles D, Devinsky O (2004) Epilepsy surgery for children with tuberous sclerosis complex. J Child Neurol 19(9):687-9

Zaroff CM, Morrison C, Ferraris N, Weiner HL, Miles DK, Devinsky O (2005) Developmental outcome of epilepsy surgery in tuberous sclerosis complex. Epileptic Disord 7(4):321-326

Resources

Epilepsy Therapy Development Project http://www.epilepsy.com/

National Institute of Neurological Disorders and Stroke, National Institutes of Health
http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm#48923109

**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