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FUNCTIONAL MRI USE IN EPILEPSY[edit]

Epilepsy[edit]

Pathophysiology[edit]

The term epilepsy covers a group of neurological disorders that involve seizure episodes that can vary from very brief and almost undetectable absences, to prolonged fits of tonic-clonic convulsions. While the exact causes and mechanisms of epilepsy are still not entirely understood, characteristic synchronised impulses of neural activity occur with decreases in the cellular requirements for the triggering of action potentials [1]. As such, excessive stimulation sweeps across regions of the brain which can then generalise across the entire brain in more severe cases.

Treatment[edit]

Epilepsy is generally managed using anticonvulsant medication, with specific medicinal choices made depending upon the type of seizure experienced by individual patients. The medication selected will be discussed between the patient and clinician, however, recent reviews have suggested that carbamazepine, phenytoin and sodium valproate are highly effective and comparable for treatment of both focal and generalised seizures [2].

Treatment-resistant seizures[edit]

Despite the broad range of antiepileptic medication that is currently available, around one in three patients continue to experience seizures [3]. In such cases, surgery can be significantly more valuable than continuing medication for the control of seizures and for improvement of quality of life. Surgery can involve resection of the seizure focal point or implantation of neuromodulatory devices [4].

Functional Magnetic Resonance Imaging[edit]

Atomic nuclei with unpaired protons or neutrons exhibit non-zero spin, thereby creating a magnetic moment. Magnetic resonance imaging (MRI) makes use of the alignment of hydrogen nuclei with a strong magnetic field. Application of a brief radio frequency pulse can result in a slight shifting of this alignment, after which the protons realign with the field. This realignment movement induces small electromagnetic changes in the field which can be detected by the MRI scanner [5]. Functional MRI (fMRI) takes this technology a step further by detecting alterations in blood flow that are associated with brain activity. Areas of increased activity require increased blood flow in what is described as a haemodynamic response [6]. Developing sufficient contrast or accurate imaging can sometimes be challenging, with resolution precision being within only a few millimetres and with a time window lasting several seconds. To combat this, techniques such as arterial spin labelling and blood-oxygen-level-dependent (BOLD) fMRI have been developed. Arterial spin labelling involves the application of an opposing magnetic field directly below the region of interest, thereby resulting in alignment of the arterial blood with the first magnetic field prior to its arrival at the region of interest. This provides a more intense contrast of the arterial blood in the image [7]. BOLD fMRI relies on the principle that active neurons require more oxygen than inactive neurons. Given that oxygenated and deoxygenated haemoglobin have differing magnetic properties (being diamagnetic and paramagnetic, respectively), regions of activity can be readily identified in direct correlation to the oxygenation level of the blood [8].

Procedures for fMRI[edit]

Blood-oxygen-level-dependent (BOLD) fMRI[edit]

Functional MRI is of considerable value for the identification of the specific region of the brain involved in the generation of focal seizures. It is considerably less invasive than intraoperative cortical stimulation or the Wada test, which involves the introduction of barbiturates into the carotid artery to determine which brain hemisphere is involved during language and memory tests [9].

Echoplanar imaging[edit]

Echoplanar imaging is one of the most common form of imaging used in fMRI studies. It is fast enough that the entire brain can be imaged in only a few seconds; however, the spatial resolution is considerably less precise than in standard anatomical MRI images. In practice, the patient is asked to perform a mental task that involves the shifting of activity from one brain region to another while a large set of images is acquired [10].

Clinical Applications[edit]

One of the key areas in which fMRI can be of benefit for patients with epilepsy is the pre-surgical assessment of brain function. Regions of the brain involved in motor and sensory representations of the body vary from one individual to another, as do specific regions for memory and language function. Pre-surgical assessment with fMRI allows the surgeon to plan any procedure to preserve function and maintain safety.

Mapping eloquent cortex[edit]

The eloquent cortex refers to the brain regions that would result in loss of function in sensory or motor control, speech and language, vision and memory. Although electrical stimulation mapping through the implantation of electrodes onto the brain is considered most reliable, fMRI provides a less invasive alternative [11].

Lateralisation of language[edit]

Involving the Broca’s and Wernicke’s areas, spoken language processing takes place through the auditory ventral stream and the auditory dorsal stream, However, whether the majority of the processing occurs on the left or right side of the brain can vary according to the individual, with some even being inconsistent with which hemisphere they use [12]. Semantic decision tasks and verbal fluency tasks should be carried out using visual as opposed to audio stimulation, as this has been shown to provide more accurate and consistent results, particularly in multilingual countries [13].

Mapping of memory[edit]

Mapping of memory is considerably more challenging than language mapping as it involves both encoding and retrieval of many different types of information and these tasks can involve activation of multiple areas of the brain. It can also be challenging to reliably separate the brain activity involved in the memory formation and recall from other cognitive processes that occur simultaneously [14]. Memory processing largely involves the mesial temporal lobe. When the seizure focus is ipsilateral to the dominant memory centre and surgery is undertaken, greater decline in memory is seen as a result [15].

Localisation of spontaneous ictal activity[edit]

While electroencephalography (EEG) provides very rapid information although it lacks a degree of spatial precision, fMRI can provide high spatial precision, albeit more slowly than EEG. The combination of these two techniques can provide efficient and accurate information about the seizure focus and is particularly valuable during the evaluation of patients with neocortical epilepsy in which EEG data can be poorly localised. Given the intrinsic connection between magnetic fields and induction of electrical currents, performing EEG within an MRI scanner is fraught with challenges. However, appropriate shielding of the EEG equipment can result in predictable signals in the EEG recording equipment, thereby allowing the simultaneous data collection [16].

Clinical Considerations[edit]

Epileptic patients who are subject to frequent seizures can have low intelligence quotients, making their performance and co-operation in difficult language and memory tasks challenging to predict. However, they are likely to be able to perform more simple motor tasks. Certain medicines can affect the levels of activation seen during fMRI image acquisition; such as, for example, carbamazepine significantly influencing the level of fMRI activation seen during visuospatial tasks [17]. Ictal and interictal activity can alter the lateralisation of certain functions, particularly mesiotemporal memory and language functions, so a degree of caution is required during the interpretation of such data [18]. Signals that are acquired during fMRI investigation can be contaminated by movement of the patient, both minor movements within the head such as the pulsation of the brain and cerebrospinal fluid, and larger movements of the whole head. Although head movement can be restricted with the use of restraints, this is not always appropriate and patients find this uncomfortable. Post-processing of data using computer-assisted realignment can reduce the impact of movement on image quality, but stimulation options that invoke less head movement is the preferred option [19].

Comparison with other Imaging Types[edit]

Positron emission tomography[edit]

Positron emission tomography (PET) makes use of a radioactive tracer such as fluorine-18 which emits positrons. Although the positrons themselves are infinitesimally short-lived, the gamma rays resulting from their interaction with electrons can be detected, leading to the production of the three-dimensional image [20]. Whilst the imaging quality from PET scans is very high, unlike fMRI it involves exposure of the patient to ionising radiation [21].

Electroencephalography[edit]

Through the use of electrodes attached to the scalp, EEG is capable of monitoring electrical activity in the brain, and is therefore a useful diagnostic tool for the diagnosis of epilepsy [22]. However, standard scalp EEG is only able to capture data on the electrical activity of the outermost few centimetres of brain activity, so localisation of any seizure focus that is deeper within the brain can require additional investigation.

Magnetoencephalography[edit]

Magnetoencephalography monitors the electrical currents of the brain by recording and mapping the magnetic fields induced by such currents. This type of investigation requires extremely sensitive equipment and is currently largely only used in research environments, although wearable systems are on the horizon with the development of quantum sensors that do not require the superconducting technology inherent in previous systems [23].  

References[edit]

  1. ^ da Silva, F. L., Blanes, W., Kalitzin, S. N., Parra, J., Suffczynski, P., & Velis, D. N. (2003). Epilepsies as Dynamical Diseases of Brain Systems: Basic Models of the Transition Between Normal and Epileptic Activity. Epilepsia, 44(s12), 72–83.
  2. ^ Nevitt, S. J., Marson, A. G., Weston, J., & Tudur Smith, C. (2018, August 9). Sodium valproate versus phenytoin monotherapy for epilepsy: An individual participant data review. Cochrane Database of Systematic Reviews, Vol. 2018
  3. ^ Eadie, M. J. (2012, December). Shortcomings in the current treatment of epilepsy. Expert Review of Neurotherapeutics, Vol. 12, pp. 1419–1427
  4. ^ Yoo, J. Y., & Panov, F. (2019, April 1). Identification and Treatment of Drug-Resistant Epilepsy. CONTINUUM Lifelong Learning in Neurology, Vol. 25, pp. 362–380
  5. ^ Moore, M. M., & Chung, T. (2017, May 1). Review of key concepts in magnetic resonance physics. Pediatric Radiology, Vol. 47, pp. 497–506
  6. ^ Thornton, R. C., van Graan, L. A., Powell, R. H., & Lemieux, L. (2016). fMRI in epilepsy. In Neuromethods (Vol. 119, pp. 741–799)
  7. ^ Telischak, N. A., Detre, J. A., & Zaharchuk, G. (2015, May 1). Arterial spin labeling MRI: Clinical applications in the brain. Journal of Magnetic Resonance Imaging, Vol. 41, pp. 1165–1180
  8. ^ Ogawa, S., Tank, D. W., Menon, R., Ellermann, J. M., Kim, S. G., Merkle, H., & Ugurbil, K. (1992). Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proceedings of the National Academy of Sciences of the United States of America, 89(13), 5951–5955
  9. ^ Hermann, B. (2005). Wada Test Failure and Cognitive Outcome. Epilepsy Currents, 5(2), 61–62
  10. ^ Kesavadas, C., & Thomas, B. (2008, August 1). Clinical applications of functional MRI in epilepsy. Indian Journal of Radiology and Imaging, Vol. 18, pp. 210–217
  11. ^ Jayakar, P., Jayakar, A., Libenson, M., Arzimanoglou, A., Rydenhag, B., Cross, J. H., Bhatia, S., Tassie, L., Lachhwani, D., & Gaillard, W. D. (2018). Epilepsy surgery near or in eloquent cortex in children-Practice patterns and recommendations for minimizing and reporting deficits. Epilepsia, 59(8), 1484–1491
  12. ^ Bradshaw, A. R., Woodhead, Z. V. J., Thompson, P. A., & Bishop, D. V. M. (2019). Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment. European Journal of Neuroscience, ejn.14623
  13. ^ Kesavadas, C., & Thomas, B. (2008, August 1). Clinical applications of functional MRI in epilepsy. Indian Journal of Radiology and Imaging, Vol. 18, pp. 210–217
  14. ^ Jokeit, H, Okujava, M., & Woermann, F. G. (2001). Memory fMRI lateralizes temporal lobe epilepsy. Neurology, 57(10), 1786–1793
  15. ^ Powell, H. W. R., Richardson, M. P., Symms, M. R., Boulby, P. A., Thompson, P. J., Duncan, J. S., & Koepp, M. J. (2008). Preoperative fMRI predicts memory decline following anterior temporal lobe resection. Journal of Neurology, Neurosurgery and Psychiatry, 79(6), 686–693
  16. ^ Krakow, K., Allen, P. J., Symms, M. R., Lemieux, L., Josephs, O., & Fish, D. R. (2000). EEG recording during fMRI experiments: image quality. Human Brain Mapping, 10(1), 10–15
  17. ^ Jokeit, H, Okujava, M., & Woermann, F. G. (2001). Carbamazepine reduces memory induced activation of mesial temporal lobe structures: A pharmacological fMRI-study. BMC Neurology, 1
  18. ^ Jayakar, P., Bernal, B., Santiago Medina, L., & Altman, N. (2002). False lateralization of language cortex on functional MRI after a cluster of focal seizures. Neurology, 58(3), 490–492
  19. ^ Kesavadas, C., & Thomas, B. (2008, August 1). Clinical applications of functional MRI in epilepsy. Indian Journal of Radiology and Imaging, Vol. 18, pp. 210–217
  20. ^ Heurling, K., Leuzy, A., Jonasson, M., Frick, A., Zimmer, E. R., Nordberg, A., & Lubberink, M. (2017, September 1). Quantitative positron emission tomography in brain research. Brain Research, Vol. 1670, pp. 220–234
  21. ^ Kelloff, G. J., Hoffman, J. M., Johnson, B., Scher, H. I., Siegel, B. A., Cheng, E. Y., Cheston, B. D., O'Shaughnessy, Y., Guyton, K. Z., Mankoff, D. A., Shankar, L., Larson, S. M., Sigman, C. C., Schilsky, R. L., & Sullivan, D. C. (2005, April 15). Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clinical Cancer Research, Vol. 11, pp. 2785–2808
  22. ^ Tatum, W. O. (2014). Handbook of EEG interpretation. New York: Demos Medical. Telischak, N. A., Detre, J. A., & Zaharchuk, G. (2015, May 1). Arterial spin labeling MRI: Clinical applications in the brain. Journal of Magnetic Resonance Imaging, Vol. 41, pp. 1165–1180
  23. ^ Boto, E., Holmes, N., Leggett, J., Roberts, G., Shah, V., Meyer, S. S., Munoz, L. D., Mullinger, K. J., Tierney, T. M., Bestmann, S., Barnes, G. R., Bowtell, R., & Brookes, M. J. (2018). Moving magnetoencephalography towards real-world applications with a wearable system. Nature, 555(7698), 657–661

Boto, E., Holmes, N., Leggett, J., Roberts, G., Shah, V., Meyer, S. S., Munoz, L. D., Mullinger, K. J., Tierney, T. M., Bestmann, S., Barnes, G. R., Bowtell, R., & Brookes, M. J. (2018). Moving magnetoencephalography towards real-world applications with a wearable system. Nature, 555(7698), 657–661. https://doi.org/10.1038/nature26147 Bradshaw, A. R., Woodhead, Z. V. J., Thompson, P. A., & Bishop, D. V. M. (2019). Investigation into inconsistent lateralisation of language functions as a potential risk factor for language impairment. European Journal of Neuroscience, ejn.14623. https://doi.org/10.1111/ejn.14623 da Silva, F. L., Blanes, W., Kalitzin, S. N., Parra, J., Suffczynski, P., & Velis, D. N. (2003). Epilepsies as Dynamical Diseases of Brain Systems: Basic Models of the Transition Between Normal and Epileptic Activity. Epilepsia, 44(s12), 72–83. https://doi.org/10.1111/j.0013-9580.2003.12005.x Duncan, J. S., Sander, J. W., Sisodiya, S. M., & Walker, M. C. (2006, April 1). Adult epilepsy. Lancet, Vol. 367, pp. 1087–1100. https://doi.org/10.1016/S0140-6736(06)68477-8 Eadie, M. J. (2012, December). Shortcomings in the current treatment of epilepsy. Expert Review of Neurotherapeutics, Vol. 12, pp. 1419–1427. https://doi.org/10.1586/ern.12.129 Hermann, B. (2005). Wada Test Failure and Cognitive Outcome. Epilepsy Currents, 5(2), 61–62. https://doi.org/10.1111/j.1535-7597.2005.05206.x Heurling, K., Leuzy, A., Jonasson, M., Frick, A., Zimmer, E. R., Nordberg, A., & Lubberink, M. (2017, September 1). Quantitative positron emission tomography in brain research. Brain Research, Vol. 1670, pp. 220–234. https://doi.org/10.1016/j.brainres.2017.06.022 Jayakar, P., Bernal, B., Santiago Medina, L., & Altman, N. (2002). False lateralization of language cortex on functional MRI after a cluster of focal seizures. Neurology, 58(3), 490–492. https://doi.org/10.1212/wnl.58.3.490 Jayakar, P., Jayakar, A., Libenson, M., Arzimanoglou, A., Rydenhag, B., Cross, J. H., Bhatia, S., Tassie, L., Lachhwani, D., & Gaillard, W. D. (2018). Epilepsy surgery near or in eloquent cortex in children-Practice patterns and recommendations for minimizing and reporting deficits. Epilepsia, 59(8), 1484–1491. https://doi.org/10.1111/epi.14510 Jokeit, H, Okujava, M., & Woermann, F. G. (2001). Memory fMRI lateralizes temporal lobe epilepsy. Neurology, 57(10), 1786–1793. https://doi.org/10.1212/wnl.57.10.1786 Jokeit, H, Okujava, M., & Woermann, F. G. (2001). Carbamazepine reduces memory induced activation of mesial temporal lobe structures: A pharmacological fMRI-study. BMC Neurology, 1. https://doi.org/10.1186/1471-2377-1-6 Kelloff, G. J., Hoffman, J. M., Johnson, B., Scher, H. I., Siegel, B. A., Cheng, E. Y., Cheston, B. D., O'Shaughnessy, Y., Guyton, K. Z., Mankoff, D. A., Shankar, L., Larson, S. M., Sigman, C. C., Schilsky, R. L., & Sullivan, D. C. (2005, April 15). Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clinical Cancer Research, Vol. 11, pp. 2785–2808. https://doi.org/10.1158/1078-0432.CCR-04-2626 Kesavadas, C., & Thomas, B. (2008, August 1). Clinical applications of functional MRI in epilepsy. Indian Journal of Radiology and Imaging, Vol. 18, pp. 210–217. https://doi.org/10.4103/0971-3026.41829 Krakow, K., Allen, P. J., Symms, M. R., Lemieux, L., Josephs, O., & Fish, D. R. (2000). EEG recording during fMRI experiments: image quality. Human Brain Mapping, 10(1), 10–15. https://doi.org/10.1002/(sici)1097-0193(200005)10:1<10::aid-hbm20>3.0.co;2-t Loring, D. W. (1997). Neuropsychological Evaluation in Epilepsy Surgery. Epilepsia, 38(s4), S18–S23. https://doi.org/10.1111/j.1528-1157.1997.tb04535.x Moore, M. M., & Chung, T. (2017, May 1). Review of key concepts in magnetic resonance physics. Pediatric Radiology, Vol. 47, pp. 497–506. https://doi.org/10.1007/s00247-017-3791-3 Nakai, Y., Jeong, J. W., Brown, E. C., Rothermel, R., Kojima, K., Kambara, T., Shah, A., Mittal, S., Sood, S., & Asano, E. (2017). Three- and four-dimensional mapping of speech and language in patients with epilepsy. Brain, 140(5), 1351–1370. https://doi.org/10.1093/brain/awx051 Nevitt, S. J., Marson, A. G., & Smith, C. T. (2019, July 18). Carbamazepine versus phenytoin monotherapy for epilepsy: An individual participant data review. Cochrane Database of Systematic Reviews, Vol. 2019. https://doi.org/10.1002/14651858.CD001911.pub4 Nevitt, S. J., Marson, A. G., Weston, J., & Tudur Smith, C. (2018, August 9). Sodium valproate versus phenytoin monotherapy for epilepsy: An individual participant data review. Cochrane Database of Systematic Reviews, Vol. 2018. https://doi.org/10.1002/14651858.CD001769.pub4 Ogawa, S., Tank, D. W., Menon, R., Ellermann, J. M., Kim, S. G., Merkle, H., & Ugurbil, K. (1992). Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proceedings of the National Academy of Sciences of the United States of America, 89(13), 5951–5955. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1631079 Powell, H. W. R., Richardson, M. P., Symms, M. R., Boulby, P. A., Thompson, P. J., Duncan, J. S., & Koepp, M. J. (2008). Preoperative fMRI predicts memory decline following anterior temporal lobe resection. Journal of Neurology, Neurosurgery and Psychiatry, 79(6), 686–693. https://doi.org/10.1136/jnnp.2007.115139 Tatum, W. O. (2014). Handbook of EEG interpretation. New York: Demos Medical. Telischak, N. A., Detre, J. A., & Zaharchuk, G. (2015, May 1). Arterial spin labeling MRI: Clinical applications in the brain. Journal of Magnetic Resonance Imaging, Vol. 41, pp. 1165–1180. https://doi.org/10.1002/jmri.24751 Thornton, R. C., van Graan, L. A., Powell, R. H., & Lemieux, L. (2016). fMRI in epilepsy. In Neuromethods (Vol. 119, pp. 741–799). https://doi.org/10.1007/978-1-4939-5611-1_24 Yoo, J. Y., & Panov, F. (2019, April 1). Identification and Treatment of Drug-Resistant Epilepsy. CONTINUUM Lifelong Learning in Neurology, Vol. 25, pp. 362–380. https://doi.org/10.1212/CON.0000000000000710

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