Fits! Jason Richards, MD Resident, UNC Dept. of Neurology One year - - PowerPoint PPT Presentation

Fits!

Jason Richards, MD Resident, UNC Dept. of Neurology

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One year ago...

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Chapel Hill, NC London, UK

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Chapel Hill, NC London, UK

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Chapel Hill, NC London, UK

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Chapel Hill, NC London, UK

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Intern House officer

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Resident Registrar

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Attending Consultant

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Seizures Fits

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http://shibleyrahman.com/dr-shibley-rahman-viewpoint/i-am-finally-discharged-from-queen-square/

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Stephen McKay “Statue of Queen Charlotte in the Square's gardens” https://en.wikipedia.org/wiki/Queen_Square,_London#/media/File:Queen_Charlotte,_Queen_Square.jpg

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http://www.uclh.nhs.uk/OurServices/OurHospitals/NHNN/Pages/Home.aspx

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http://www.julesthorntrust.org.uk/about_history.html

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http://www.epilepsysociety.org.uk/epilepsy-society-research-centre#.Vjw_ItKrTuQ

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https://en.wikipedia.org/wiki/William_Gowers_(neurologist)#/media/File:William_Richard_Gowers.jpg

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https://en.wikipedia.org/wiki/Gowers%27_sign#/media/File:Gower%27s_Sign.png

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While away I noticed many differences:

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While away I noticed many differences:

Cultural

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While away I noticed many differences:

Cultural Health systems

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While away I noticed many differences:

Wada fMRI

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Overview

• Epilepsy is one of the most common

neurologic diseases

» affects 0.5 - 1% of the population » 60% are focal epilepsies

• 20% of patients with focal epilepsy are drug

resistant » Defined as continued seizures despite two appropriate AEDs with good compliance

Gelžinienė, Giedrė, et al. "Presurgical Evaluation of Epilepsy Patients." Medicina (Kaunas) 44.8 (2008): 585-92. Web.

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Overview

• Chance of success decreases with successive

drug trials » second AED response rate 14% » Third AED response rate 5%

Gelžinienė, Giedrė, et al. "Presurgical Evaluation of Epilepsy Patients." Medicina (Kaunas) 44.8 (2008): 585-92. Web.

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Epilepsy Surgery

• One of first cases performed at Queen Square

by Mr. Victor Horsley

» Patient was a 22 year old with epilepsy from a car accident » Suffering prolonged episodes of “Jacksonian” status epilepticus » In 1866, operation removed the cortical scar » Once the wound healed, the seizures resolved

Taylor, D. C. "One Hundred Years of Epilepsy Surgery: Sir Victor Horsley's Contribution." Journal of Neurology, Neurosurgery & Psychiatry 49.5 (1986): 485-88. Web.

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Epilepsy Surgery

https://en.wikipedia.org/wiki/Victor_Horsley

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Presurgical evaluation

• Careful patient selection is key for good
• utcomes

» Focal seizure onset should be established » Progressive lesions should be excluded » Resistance to medical therapy » Seizures interfering with daily life

Gelžinienė, Giedrė, et al. "Presurgical Evaluation of Epilepsy Patients." Medicina (Kaunas) 44.8 (2008): 585-92. Web.

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Presurgical Evaluation

• Optimal surgery lesions just enough tissue to

eliminate seizures

• Targeted area must not support essential

functions, such as memory, motor or language

» Testing is therefore need to precisely show the location of essential cortex

Engel, Jerome, Jr,M.D., PhD. (1996). Surgery for seizures. The New England Journal of Medicine, 334(10), 647-653.

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Wada fMRI

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Wada testing

• Test in which sodium amytal (barbiturate) is

injected into the carotid arteries » Named for Juhn Wada, a Japanese

psychiatrist » 30 patients hospitalized with psychiatric problems underwent the procedure » Each carotid artery was injected with sodium amytal, with the right being injected first » Patients became hemiparetic on the side contralateral to the injection. » Only one patient had a speech impediment with right sided injection. All had aphasia with left sided injection

Wada, Juhn A. "Clinical Experimental Observations of Carotid Artery Injections of Sodium Amytal." Brain and Cognition: 11-13. Web. 7 Nov. 2015.

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Wada testing

• Anesthesia typically lasts 4-8 minutes

» Once hemiplegia is confirmed, language testing and memory tests are performed

• Allows for localization of essential cortex

Sharan, Ashwini, Yinn Cher Ooi, John Langfitt, and Michael R. Sperling. "Intracarotid Amobarbital Procedure for Epilepsy Surgery." Epilepsy & Behavior 20.2 (2011): 209-13. Web.

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Wada testing

• Anesthetization is not always consistent due

to variations in anatomy

» Amount of flow to contralateral hemisphere can differ » Amount of posterior temporal lobe supplied by the anterior circulation is variable » Some patients have atresic anterior or posterior circulations

Sharan, Ashwini, Yinn Cher Ooi, John Langfitt, and Michael R. Sperling. "Intracarotid Amobarbital Procedure for Epilepsy Surgery." Epilepsy & Behavior 20.2 (2011): 209-13. Web.

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Wada fMRI

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MRI

Berger, Abi. BMJ 324 (2002): 35.

Atomic nuclei have magnetic orientation and spin

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MRI

Berger, Abi. BMJ 324 (2002): 35.

Atoms Atoms in magnetic field

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MRI

Berger, Abi. BMJ 324 (2002): 35.

Atoms in magnetic field

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MRI

Kim, Seong-Gi, and Seiji Ogawa. "Biophysical and Physiological Origins of Blood Oxygenation Level-dependent FMRI Signals." Journal of Cerebral Blood Flow & Metabolism J Cereb Blood Flow Metab 32.7 (2012): 1188-206. Web.

• Additional energy (in form of a radiowave)

can deflect the magnetic vector and cause resonance

• When radiowave is stopped, the magnetic

vector relaxes

• Time needed for magnetic vector to return

to resting state is T1,

• Time for spin relaxation is T2

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fMRI

Kim, Seong-Gi, and Seiji Ogawa. "Biophysical and Physiological Origins of Blood Oxygenation Level-dependent FMRI Signals." Journal of Cerebral Blood Flow & Metabolism J Cereb Blood Flow Metab 32.7 (2012): 1188-206. Web.

• Uses blood oxygenation level dependent

(BOLD) contrast

» Deoxyhemoglobin is an endogenous paramagnetic contrast agent

» Changes in local deoxyhemoglobin

concentration lead to alterations in MRI signal intensity

• Coupling between neural activity and

vascular dilation

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fMRI

Kim, Seong-Gi, and Seiji Ogawa. "Biophysical and Physiological Origins of Blood Oxygenation Level-dependent FMRI Signals." Journal of Cerebral Blood Flow & Metabolism J Cereb Blood Flow Metab 32.7 (2012): 1188-206. Web.

• Glucose metabolism and cerebral blood flow

are closely coupled

• When upstream arterioles dilate, there is a

decrease in the deoxyhemoglobin

• This decrease is the basis of the fMRI image

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fMRI

• Due to different amounts of blood and

brain in different areas, one cannot accurately compare signal between different voxels

• Possible to compare a voxel to itself

across tasks

Kim, Seong-Gi, and Seiji Ogawa. "Biophysical and Physiological Origins of Blood Oxygenation Level-dependent FMRI Signals." Journal of Cerebral Blood Flow & Metabolism J Cereb Blood Flow Metab 32.7 (2012): 1188-206. Web.

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fMRI

Duncan, John S. "Imaging in the Surgical Treatment of Epilepsy." Nature Reviews Neurology Nat Rev Neurol 6.10 (2010): 537-50. Web.

• range = language task, green = right hand motor task

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Language lateralization

• Right handed people are generally left

hemisphere language dominant

• A 1999 study by Springer at al examined this

issue using fMRI

» Recruited 100 normal subjects and 50 subjects with epilepsy » All were right handed » Performed a tone decision and a semantic decision task

Springer, J. A. "Language Dominance in Neurologically Normal and Epilepsy Subjects: A Functional MRI Study." Brain 122.11 (1999): 2033-046. Web.

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Language lateralization

Springer, J. A. "Language Dominance in Neurologically Normal and Epilepsy Subjects: A Functional MRI Study." Brain 122.11 (1999): 2033-046. Web.

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Language lateralization

• Study then generated a laterality index

» Processed a mean of 7,899 voxels per subject » Threshold above which each voxel was considered “activated” » Volume of activated voxels on the left and rights sides was computed » Laterality index was generated (LV-RV)/TV » Numbers ranged from 100 (left dominant) to

• 100 (right dominant)

Springer, J. A. "Language Dominance in Neurologically Normal and Epilepsy Subjects: A Functional MRI Study." Brain 122.11 (1999): 2033-046. Web.

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Language lateralization

Springer, J. A. "Language Dominance in Neurologically Normal and Epilepsy Subjects: A Functional MRI Study." Brain 122.11 (1999): 2033-046. Web.

Right dominant Left dominant Mixed

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Wada versus fMRI

• The two techniques are fundamentally different
• Wada testing:

» replicates a lesion » outcome is traditionally left dominance, right dominance or codominance

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

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Wada versus fMRI

• Two techniques are fundamentally different
• fMRI:

» the outcome is on a continuous scale » compares an activation task to a control task, highly important that the two tasks only differ with the use of language » Arbitrary voxel activation threshold

• To compare techniques, one must arbitrarily

define dominance data for fMRI

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

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Wada versus fMRI

• Bauer et al conducted a meta-analysis

comparing the two techniques

» Included 22 studies comparing Wada data to fMRI data with a total of 504 patients » Studies provided categorical data for Wada (left, right, both) and lateralization index for fMRI. » Commonly used cut-off points (-20, 0, 20) were used to convert LI to categorical Wada data

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

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Wada versus fMRI

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

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Wada versus fMRI

• Wada and fMRI agreed 80.55% of time
• fMRI agreed with Wada in left language

representation 94.2% time (PPV)

• fMRI agreed with Wada in right language

representation 51.1% (NPV)

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

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Handedness, fMRI and Bayes

https://en.wikipedia.org/wiki/Thomas_Bayes

Thomas Bayes (English) Statistician

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Pre-test Probability Test Post-test Probability

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

P is probability T+ is positive test result D+ is hemispheric language dominance D- is no hemispheric language dominance

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Pre-test Probability: Population studies Test: Likelihood ratio Post-test Probability

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Both studies used Wada to determine handedness

Pre-test Probability: Population studies

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Test: Likelihood ratio

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

• fMRI sensitivity and specificity are each 92.5%
• Likelihood ratio was 12.3

» LR = Sensitivity/(1-specificity)

Test: Likelihood ratio

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

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Handedness, fMRI and Bayes

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Hand Dominance Pretest probability (%) fMRI dominance Posttest probability (%) Right 80-91 Left 97 to > 99 Ambidextrous 67 Left 95-96

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Handedness, fMRI and Bayes

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

fMRI Wada Left Not left Left 333 23 Not left 49 99 Sensitivity = 0.87 Specificity = 0.81 LR+ = 4.58

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

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Handedness, fMRI and Bayes

Bauer, P. R., J. B. Reitsma, B. M. Houweling, C. H. Ferrier, and N. F. Ramsey. "Can FMRI Safely Replace the Wada Test for Preoperative Assessment of Language Lateralisation? A Meta-analysis and Systematic Review." Journal of Neurology, Neurosurgery & Psychiatry 85.5 (2013): 581-88. Web.

Sensitivity = 0.87 Specificity = 0.81 LR+ = 4.58

• Probability of left language in RH subjects

» Pre-test = 80-91% » Post-test = 95 - 98%

Medina, L. Santiago, Byron Bernal, and Jeniffer Ruiz. "Role of Functional MR in Determining Language Dominance in Epilepsy and Nonepilepsy Populations: A Bayesian Analysis 1." Radiology 242.1 (2007): 94-100. Web.

Cost and Complications

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Cost of testing

Medina, L. Santiago, Elsa Aguirre, Byron Bernal, and Nolan R. Altman. "Functional MR Imaging versus Wada Test for Evaluation of Language Lateralization: Cost Analysis." Radiology 230.1 (2004): 49-54. Web.

• Medina et al, 2004 study looking at costs

» 39 children with planned neurosurgery » Most undergoing procedure for seizure control » Undergoing preoperative Wada or fMRI » Analyzed costs related to care

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Cost of testing

Medina, L. Santiago, Elsa Aguirre, Byron Bernal, and Nolan R. Altman. "Functional MR Imaging versus Wada Test for Evaluation of Language Lateralization: Cost Analysis." Radiology 230.1 (2004): 49-54. Web.

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Cost of testing

Medina, L. Santiago, Elsa Aguirre, Byron Bernal, and Nolan R. Altman. "Functional MR Imaging versus Wada Test for Evaluation of Language Lateralization: Cost Analysis." Radiology 230.1 (2004): 49-54. Web.

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Cost of testing

Medina, L. Santiago, Elsa Aguirre, Byron Bernal, and Nolan R. Altman. "Functional MR Imaging versus Wada Test for Evaluation of Language Lateralization: Cost Analysis." Radiology 230.1 (2004): 49-54. Web.

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Wada testing complications

• 2005 European study by Hagg et al:

» Surveyed European epilepsy centers about Wada testing and complications » A total of 1,373 Wada tests were performed by 15 centers between 2000 and 2005 » Ratio of Wada tests to surgeries fell

• 56% in 2000 and 35% in 2005

» 15 complications (1.09%) were seen » 5 compliations (0.36%) with permanent morbidity

Haag A, Knake S, Hamer HM, et al. The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures. Epilepsy Behav 2008;13:83–89.

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Wada testing complications

Haag A, Knake S, Hamer HM, et al. The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures. Epilepsy Behav 2008;13:83–89.

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Wada testing complications

• Study at University of Michigan from 2015

» Reviewed 431 patients who underwent Wada testing » Data collected on occurrence of any adverse clinical event and events thought to be complications to the procedure » Neurologic changes related to the patient’s underlying illness were not considered procedure-related complications. » 25 patients (5.8%) had an adverse event » 9 patients (2.1%) had events classified as complications

Beimer, Nicholas J., Henry A. Buchtel, and Simon M. Glynn. "One Center's Experience with Complications during the Wada Test." Epilepsia 56.8 (2015): n. pag. Web.

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fMRI complications

1) Berger, Abi. BMJ 324 (2002): 35.

• No known biological hazards of fMRI 1
• MRI does not use harmful radiation 1
• Deoxyhemoglobin is an endogenous

molecule, no contrast injected 2

2) Kim, Seong-Gi, and Seiji Ogawa. "Biophysical and Physiological Origins of Blood Oxygenation Level-dependent FMRI Signals." Journal of Cerebral Blood Flow & Metabolism J Cereb Blood Flow Metab 32.7 (2012): 1188-206. Web.

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Conclusions

Wada fMRI

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Conclusions

• fMRI agreed with Wada in left language

representation 94.2% time

• Given left language representation on fMRI

in a right handed patient, 95 to 99% chance Wada will show left language

• Wada has a 1-2% complication rate
• Wada costs over 3.7 times as much as fMRI

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Conclusions

• Use of Wada is decreasing

» A 1993 study found that up to 85% of centers performed a Wada on all preoperative temporal lobe epilepsy assessments » A 2008 study found that only 12% of centers used Wada for all preoperative evaluations » 2008 study demonstrated more than a third “never or rarely” used Wada testing

Sharan, Ashwini, Yinn Cher Ooi, John Langfitt, and Michael R. Sperling. "Intracarotid Amobarbital Procedure for Epilepsy Surgery." Epilepsy & Behavior 20.2 (2011): 209-13. Web.

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Conclusions

fMRI? fMRI

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Thank you!

• Dr. Browner
• Dr. Shin
• Shay Slifko and everyone in the UNC OIA
• The numerous NHS registrars and fellows
• The NHNN consultants, particularly: Dr. Wehner,
• Dr. Diehl, Prof. Sander, Prof. Duncan, Prof.

Sisodiya and Dr. Jarman

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Resident’s Question Time