Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

Robert Fisher; Vicenta Salanova; Thomas Witt; Robert Worth; Thomas Henry; Robert Gross; Kalarickal Oommen; Ivan Osorio; Jules Nazzaro; Douglas Labar; Michael Kaplitt; Michael Sperling; Evan Sandok; John Neal; Adrian Handforth; John Stern; Antonio DeSalles; Steve Chung; Andrew Shetter; Donna Bergen; Roy Bakay; Jaimie Henderson; Jacqueline French; Gordon Baltuch; William Rosenfeld; Andrew Youkilis; William Marks; Paul Garcia; Nicolas Barbaro; Nathan Fountain; Carl Bazil; Robert Goodman; Guy McKhann; K. Babu Krishnamurthy; Steven Papavassiliou; Charles Epstein; John Pollard; Lisa Tonder; Joan Grebin; Robert Coffey; Nina Graves; Marc Dichter; William Elias; Paul Francel; Robert Frysinger; Kevin Graber; John Grant; Gary Heit; Susan Herman; Padmaja Kandula; Andres Kanner; Jeanne Ann King; Eric Kobylarz; Karen Lapp; Suzette LaRoche; Susan Lippmann; Rama Maganti; Timothy Mapstone; Dragos Sabau; Lara Schrader; Ashwini Sharan; Michael Smith; David Treiman; Steve Wilkinson; Steven Wong; Andro Zangaladze; Shelley Adderley; Brian Bridges; Mimi Callanan; Dawn Cordero; Cecelia Fields; Megan Johnson; MaryAnn Kavalir; Patsy Kretschmar; Carol Macpherson; Kathy Mancl; Marsha Manley; Stephanie Marsh; Jean Montgomery; Pam Mundt; Phani Priya Nekkalapu; Bill Nikolov; Bruce Palmer; Linda Perdue; Alison Randall; David Smith; Linda Smith; Kristen Strybing; Leigh Stott; Robin Taylor; Stacy Thompson; Zornitza Timenova; Bree Vogelsong; Virginia Balbona; Donna Broshek; Deborah Cahn-Weiner; Lisa Clift; Mary Davidson; Evan Drake; Sally Frutiger; Lynette Featherstone; Chris Grote; Dan Han; Dianne Henry; Jessica Horsfall; Andrea Hovick; Jennifer Gray; David Kareken; Kristin Kirlin; Debbie Livingood; Michele Meyer; Nancy Minniti; Jeannine Morrone Strupinsky; William Schultz; James Scott; Joseph Tracy; Stuart Waltonen; Penelope Ziefert; Carla Van Amburg; Mark Burdelle; Sandra Clements; Robert Cox; Raeleen Dolin; Michelle Fulk; Harinder R. Kaur; Lawrence Hirsch; Thomas Hoeppner; Andrea Hurt; Mary Komosa; Scott Krahl; Laura Ponticello; Mark Quigg; Helene Quinn; Marvin Rossi; Patty Schaefer; Christopher Skidmore; Diane Sundstrom; Patricia Trudeau; Monica Volz; Norman Wang; Lynette Will; Carol Young

doi:10.1111/j.1528-1167.2010.02536.x

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

Robert Fisher, Vicenta Salanova, Thomas Witt, Robert Worth, Thomas Henry, Robert Gross, Kalarickal Oommen, Ivan Osorio, Jules Nazzaro, Douglas Labar, Michael Kaplitt, Michael Sperling, Evan Sandok, John Neal, Adrian Handforth, John Stern, Antonio DeSalles, Steve Chung, Andrew Shetter, Donna BergenRoy Bakay, Jaimie Henderson, Jacqueline French, Gordon Baltuch, William Rosenfeld, Andrew Youkilis, William Marks, Paul Garcia, Nicolas Barbaro, Nathan Fountain, Carl Bazil, Robert Goodman, Guy McKhann, K. Babu Krishnamurthy, Steven Papavassiliou, Charles Epstein, John Pollard, Lisa Tonder, Joan Grebin, Robert Coffey, Nina Graves, Marc Dichter, William Elias, Paul Francel, Robert Frysinger, Kevin Graber, John Grant, Gary Heit, Susan Herman, Padmaja Kandula, Andres Kanner, Jeanne Ann King, Eric Kobylarz, Karen Lapp, Suzette LaRoche, Susan Lippmann, Rama Maganti, Timothy Mapstone, Dragos Sabau, Lara Schrader, Ashwini Sharan, Michael Smith, David Treiman, Steve Wilkinson, Steven Wong, Andro Zangaladze, Shelley Adderley, Brian Bridges, Mimi Callanan, Dawn Cordero, Cecelia Fields, Megan Johnson, MaryAnn Kavalir, Patsy Kretschmar, Carol Macpherson, Kathy Mancl, Marsha Manley, Stephanie Marsh, Jean Montgomery, Pam Mundt, Phani Priya Nekkalapu, Bill Nikolov, Bruce Palmer, Linda Perdue, Alison Randall, David Smith, Linda Smith, Kristen Strybing, Leigh Stott, Robin Taylor, Stacy Thompson, Zornitza Timenova, Bree Vogelsong, Virginia Balbona, Donna Broshek, Deborah Cahn-Weiner, Lisa Clift, Mary Davidson, Evan Drake, Sally Frutiger, Lynette Featherstone, Chris Grote, Dan Han, Dianne Henry, Jessica Horsfall, Andrea Hovick, Jennifer Gray, David Kareken, Kristin Kirlin, Debbie Livingood, Michele Meyer, Nancy Minniti, Jeannine Morrone Strupinsky, William Schultz, James Scott, Joseph Tracy, Stuart Waltonen, Penelope Ziefert, Carla Van Amburg, Mark Burdelle, Sandra Clements, Robert Cox, Raeleen Dolin, Michelle Fulk, Harinder R. Kaur, Lawrence Hirsch, Thomas Hoeppner, Andrea Hurt, Mary Komosa, Scott Krahl, Laura Ponticello, Mark Quigg, Helene Quinn, Marvin Rossi, Patty Schaefer, Christopher Skidmore, Diane Sundstrom, Patricia Trudeau, Monica Volz, Norman Wang, Lynette Will, Carol Young

Neurology

Research output: Contribution to journal › Article › peer-review

1357 Scopus citations

Abstract

Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

Original language	English (US)
Pages (from-to)	899-908
Number of pages	10
Journal	Epilepsia
Volume	51
Issue number	5
DOIs	https://doi.org/10.1111/j.1528-1167.2010.02536.x
State	Published - May 2010

Bibliographical note

Funding Information:
Dr. Imrey reports nonfinancial support from the Task Force on Design and Analysis of Oral Health Research and the Foundation for the Task Force on Design and Analysis of Oral Health Research all outside the submitted work.

Keywords

Deep brain stimulation
Epilepsy
Epilepsy surgery
Seizures
Thalamus

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10.1111/j.1528-1167.2010.02536.x

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Fisher, R., Salanova, V., Witt, T., Worth, R., Henry, T., Gross, R., Oommen, K., Osorio, I., Nazzaro, J., Labar, D., Kaplitt, M., Sperling, M., Sandok, E., Neal, J., Handforth, A., Stern, J., DeSalles, A., Chung, S., Shetter, A., ... Young, C. (2010). Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia, 51(5), 899-908. https://doi.org/10.1111/j.1528-1167.2010.02536.x

Fisher, R, Salanova, V, Witt, T, Worth, R, Henry, T, Gross, R, Oommen, K, Osorio, I, Nazzaro, J, Labar, D, Kaplitt, M, Sperling, M, Sandok, E, Neal, J, Handforth, A, Stern, J, DeSalles, A, Chung, S, Shetter, A, Bergen, D, Bakay, R, Henderson, J, French, J, Baltuch, G, Rosenfeld, W, Youkilis, A, Marks, W, Garcia, P, Barbaro, N, Fountain, N, Bazil, C, Goodman, R, McKhann, G, Krishnamurthy, KB, Papavassiliou, S, Epstein, C, Pollard, J, Tonder, L, Grebin, J, Coffey, R, Graves, N, Dichter, M, Elias, W, Francel, P, Frysinger, R, Graber, K, Grant, J, Heit, G, Herman, S, Kandula, P, Kanner, A, King, JA, Kobylarz, E, Lapp, K, LaRoche, S, Lippmann, S, Maganti, R, Mapstone, T, Sabau, D, Schrader, L, Sharan, A, Smith, M, Treiman, D, Wilkinson, S, Wong, S, Zangaladze, A, Adderley, S, Bridges, B, Callanan, M, Cordero, D, Fields, C, Johnson, M, Kavalir, M, Kretschmar, P, Macpherson, C, Mancl, K, Manley, M, Marsh, S, Montgomery, J, Mundt, P, Nekkalapu, PP, Nikolov, B, Palmer, B, Perdue, L, Randall, A, Smith, D, Smith, L, Strybing, K, Stott, L, Taylor, R, Thompson, S, Timenova, Z, Vogelsong, B, Balbona, V, Broshek, D, Cahn-Weiner, D, Clift, L, Davidson, M, Drake, E, Frutiger, S, Featherstone, L, Grote, C, Han, D, Henry, D, Horsfall, J, Hovick, A, Gray, J, Kareken, D, Kirlin, K, Livingood, D, Meyer, M, Minniti, N, Strupinsky, JM, Schultz, W, Scott, J, Tracy, J, Waltonen, S, Ziefert, P, Van Amburg, C, Burdelle, M, Clements, S, Cox, R, Dolin, R, Fulk, M, Kaur, HR, Hirsch, L, Hoeppner, T, Hurt, A, Komosa, M, Krahl, S, Ponticello, L, Quigg, M, Quinn, H, Rossi, M, Schaefer, P, Skidmore, C, Sundstrom, D, Trudeau, P, Volz, M, Wang, N, Will, L & Young, C 2010, 'Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy', Epilepsia, vol. 51, no. 5, pp. 899-908. https://doi.org/10.1111/j.1528-1167.2010.02536.x

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abstract = "Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and {"}most severe{"} seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.",

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author = "Robert Fisher and Vicenta Salanova and Thomas Witt and Robert Worth and Thomas Henry and Robert Gross and Kalarickal Oommen and Ivan Osorio and Jules Nazzaro and Douglas Labar and Michael Kaplitt and Michael Sperling and Evan Sandok and John Neal and Adrian Handforth and John Stern and Antonio DeSalles and Steve Chung and Andrew Shetter and Donna Bergen and Roy Bakay and Jaimie Henderson and Jacqueline French and Gordon Baltuch and William Rosenfeld and Andrew Youkilis and William Marks and Paul Garcia and Nicolas Barbaro and Nathan Fountain and Carl Bazil and Robert Goodman and Guy McKhann and Krishnamurthy, {K. Babu} and Steven Papavassiliou and Charles Epstein and John Pollard and Lisa Tonder and Joan Grebin and Robert Coffey and Nina Graves and Marc Dichter and William Elias and Paul Francel and Robert Frysinger and Kevin Graber and John Grant and Gary Heit and Susan Herman and Padmaja Kandula and Andres Kanner and King, {Jeanne Ann} and Eric Kobylarz and Karen Lapp and Suzette LaRoche and Susan Lippmann and Rama Maganti and Timothy Mapstone and Dragos Sabau and Lara Schrader and Ashwini Sharan and Michael Smith and David Treiman and Steve Wilkinson and Steven Wong and Andro Zangaladze and Shelley Adderley and Brian Bridges and Mimi Callanan and Dawn Cordero and Cecelia Fields and Megan Johnson and MaryAnn Kavalir and Patsy Kretschmar and Carol Macpherson and Kathy Mancl and Marsha Manley and Stephanie Marsh and Jean Montgomery and Pam Mundt and Nekkalapu, {Phani Priya} and Bill Nikolov and Bruce Palmer and Linda Perdue and Alison Randall and David Smith and Linda Smith and Kristen Strybing and Leigh Stott and Robin Taylor and Stacy Thompson and Zornitza Timenova and Bree Vogelsong and Virginia Balbona and Donna Broshek and Deborah Cahn-Weiner and Lisa Clift and Mary Davidson and Evan Drake and Sally Frutiger and Lynette Featherstone and Chris Grote and Dan Han and Dianne Henry and Jessica Horsfall and Andrea Hovick and Jennifer Gray and David Kareken and Kristin Kirlin and Debbie Livingood and Michele Meyer and Nancy Minniti and Strupinsky, {Jeannine Morrone} and William Schultz and James Scott and Joseph Tracy and Stuart Waltonen and Penelope Ziefert and {Van Amburg}, Carla and Mark Burdelle and Sandra Clements and Robert Cox and Raeleen Dolin and Michelle Fulk and Kaur, {Harinder R.} and Lawrence Hirsch and Thomas Hoeppner and Andrea Hurt and Mary Komosa and Scott Krahl and Laura Ponticello and Mark Quigg and Helene Quinn and Marvin Rossi and Patty Schaefer and Christopher Skidmore and Diane Sundstrom and Patricia Trudeau and Monica Volz and Norman Wang and Lynette Will and Carol Young",

note = "Funding Information: Dr. Imrey reports nonfinancial support from the Task Force on Design and Analysis of Oral Health Research and the Foundation for the Task Force on Design and Analysis of Oral Health Research all outside the submitted work.",

year = "2010",

month = may,

doi = "10.1111/j.1528-1167.2010.02536.x",

language = "English (US)",

volume = "51",

pages = "899--908",

journal = "Epilepsia",

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T1 - Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

AU - Fisher, Robert

AU - Salanova, Vicenta

AU - Witt, Thomas

AU - Worth, Robert

AU - Henry, Thomas

AU - Gross, Robert

AU - Oommen, Kalarickal

AU - Osorio, Ivan

AU - Nazzaro, Jules

AU - Labar, Douglas

AU - Kaplitt, Michael

AU - Sperling, Michael

AU - Sandok, Evan

AU - Neal, John

AU - Handforth, Adrian

AU - Stern, John

AU - DeSalles, Antonio

AU - Chung, Steve

AU - Shetter, Andrew

AU - Bergen, Donna

AU - Bakay, Roy

AU - Henderson, Jaimie

AU - French, Jacqueline

AU - Baltuch, Gordon

AU - Rosenfeld, William

AU - Youkilis, Andrew

AU - Marks, William

AU - Garcia, Paul

AU - Barbaro, Nicolas

AU - Fountain, Nathan

AU - Bazil, Carl

AU - Goodman, Robert

AU - McKhann, Guy

AU - Krishnamurthy, K. Babu

AU - Papavassiliou, Steven

AU - Epstein, Charles

AU - Pollard, John

AU - Tonder, Lisa

AU - Grebin, Joan

AU - Coffey, Robert

AU - Graves, Nina

AU - Dichter, Marc

AU - Elias, William

AU - Francel, Paul

AU - Frysinger, Robert

AU - Graber, Kevin

AU - Grant, John

AU - Heit, Gary

AU - Herman, Susan

AU - Kandula, Padmaja

AU - Kanner, Andres

AU - King, Jeanne Ann

AU - Kobylarz, Eric

AU - Lapp, Karen

AU - LaRoche, Suzette

AU - Lippmann, Susan

AU - Maganti, Rama

AU - Mapstone, Timothy

AU - Sabau, Dragos

AU - Schrader, Lara

AU - Sharan, Ashwini

AU - Smith, Michael

AU - Treiman, David

AU - Wilkinson, Steve

AU - Wong, Steven

AU - Zangaladze, Andro

AU - Adderley, Shelley

AU - Bridges, Brian

AU - Callanan, Mimi

AU - Cordero, Dawn

AU - Fields, Cecelia

AU - Johnson, Megan

AU - Kavalir, MaryAnn

AU - Kretschmar, Patsy

AU - Macpherson, Carol

AU - Mancl, Kathy

AU - Manley, Marsha

AU - Marsh, Stephanie

AU - Montgomery, Jean

AU - Mundt, Pam

AU - Nekkalapu, Phani Priya

AU - Nikolov, Bill

AU - Palmer, Bruce

AU - Perdue, Linda

AU - Randall, Alison

AU - Smith, David

AU - Smith, Linda

AU - Strybing, Kristen

AU - Stott, Leigh

AU - Taylor, Robin

AU - Thompson, Stacy

AU - Timenova, Zornitza

AU - Vogelsong, Bree

AU - Balbona, Virginia

AU - Broshek, Donna

AU - Cahn-Weiner, Deborah

AU - Clift, Lisa

AU - Davidson, Mary

AU - Drake, Evan

AU - Frutiger, Sally

AU - Featherstone, Lynette

AU - Grote, Chris

AU - Han, Dan

AU - Henry, Dianne

AU - Horsfall, Jessica

AU - Hovick, Andrea

AU - Gray, Jennifer

AU - Kareken, David

AU - Kirlin, Kristin

AU - Livingood, Debbie

AU - Meyer, Michele

AU - Minniti, Nancy

AU - Strupinsky, Jeannine Morrone

AU - Schultz, William

AU - Scott, James

AU - Tracy, Joseph

AU - Waltonen, Stuart

AU - Ziefert, Penelope

AU - Van Amburg, Carla

AU - Burdelle, Mark

AU - Clements, Sandra

AU - Cox, Robert

AU - Dolin, Raeleen

AU - Fulk, Michelle

AU - Kaur, Harinder R.

AU - Hirsch, Lawrence

AU - Hoeppner, Thomas

AU - Hurt, Andrea

AU - Komosa, Mary

AU - Krahl, Scott

AU - Ponticello, Laura

AU - Quigg, Mark

AU - Quinn, Helene

AU - Rossi, Marvin

AU - Schaefer, Patty

AU - Skidmore, Christopher

AU - Sundstrom, Diane

AU - Trudeau, Patricia

AU - Volz, Monica

AU - Wang, Norman

AU - Will, Lynette

AU - Young, Carol

N1 - Funding Information: Dr. Imrey reports nonfinancial support from the Task Force on Design and Analysis of Oral Health Research and the Foundation for the Task Force on Design and Analysis of Oral Health Research all outside the submitted work.

PY - 2010/5

Y1 - 2010/5

N2 - Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

AB - Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

KW - Deep brain stimulation

KW - Epilepsy

KW - Epilepsy surgery

KW - Seizures

KW - Thalamus

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DO - 10.1111/j.1528-1167.2010.02536.x

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AN - SCOPUS:77951546450

SN - 0013-9580

VL - 51

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EP - 908

JO - Epilepsia

JF - Epilepsia

IS - 5

ER -

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

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