- Email: [email protected]
Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder
5
Amiral J, Marfaing KA, Wolf M, et al. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996; 88: 410–16.
Blutbank, Charité Campus Virchow-Klinikum, D-13353 Berlin, Germany (O Meyer MD, Prof A Salama MD); and DiaMed AG, Cressier sur Morat, Switzerland (N Pittet MD, P Schwind PhD) Correspondence to: Dr O Meyer (e-mail: [email protected])
Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder Bart Nuttin, Paul Cosyns, Hilde Demeulemeester, Jan Gybels, Björn Meyerson Chronic electrical stimulation instead of bilateral capsulotomy was done in four selected patients with long-standing treatment-resistant obsessive-compulsive disorder. In three of them beneficial effects were observed.
Stereotactic interventions creating bilateral lesions in specific regions of the brain may be beneficial for some patients with long-standing treatment-resistant obsessive-compulsive disorder (OCD). Such lesions are irreversible; we explored the possibility of replacing this approach by chronic electrical stimulation via implanted electrodes. In four patients with severe OCD, quadripolar electrodes were stereotactically implanted in the anterior limbs of the internal capsules, one on each side. The selected stimulation targets were identical to those aimed for in capsulotomy. 1 Patient selection criteria were met. 2,3 The study protocol was approved by the local hospital ethics committees and was in accordance with the Helsinki Declaration of 1975 (revision 1983). In three patients, some beneficial effects were seen. One of them, a 39-year-old woman suffering from extremely severe OCD for more than 20 years, reported when stimulation was on, an almost instantaneous feeling of being relieved of anxiety and obsessive thinking, which disappeared after turning the stimulation off. She was continuously stimulated for 2 weeks and her parents reported that about 90% of her compulsive behaviour and rituals had vanished. In order to further assess the effects of stimulation, she was exposed to a structured test situation according to a double-blind protocol. Stimulation was applied with 100 Hz, a pulse width of 210 ms and all four contacts of the Model 3887 Pisces Quad Compact electrode (Medtronic Inc, Minneapolis) serving as cathode and the stimulator case as anode. The stimulator was set on (n=4, amplitude 4.7V) or off (n=4) in random order. The patient could not tell whether the stimulator was on or off. Thereafter the stimulator was set on (n=2, amplitude 5V) or off (n=2) in random order. The latter amplitude caused a headache, which disappeared after 10 s. This sensation probably let the patient know that the stimulator was on during these test sessions. During each of the 12 test sessions the same two standardised psychological tests were performed, in the same order (Profile of Mood States [POMS]4 and BourdonWiersma). A double-blind clinical assessment of the patient was made by six independent psychiatric residents with a video recording of the six stimulation-on and six stimulationoff sessions in random order. They were asked to rate relevant items from 0 (not present) to 3 (clearly present) for each of the 12 sessions. None of the results from the first eight test sessions were different from those of the last four
1526
test sessions. Ratings increased for the desirable symptoms social contact, communication, flow of ideas, assertiveness and mobility (the median scores for all of these items were 1 in stimulation-off versus 2 in stimulation-on). Ratings for doubt (median scores 2 in off, 1 in on) decreased during stimulation (p<0·05, Mann Whitney U test and Kendall’s coefficient of concordance). The vigour scale of the POMS increased during stimulation (mean scores: 1·67 in off vs 6·50 in on). Sustained attention assessed by the BourdonWiersma test did not change. These observations indicate that acute capsular stimulation can induce relevant beneficial effects in OCD and suggest that long-term stimulation may be useful in the management of treatment-resistant forms of this disease. Dedicated to the late Prof Per Mindus. We thank S Andréewitch, F Gielen, C Vankerckhoven, R Cluydts, L Gabriels, and K Martens for collaboration; K Mullet and B Linderoth for the fruitful discussions, P De Sutter for technical assistance, and C Plets for support. FWO (project nr G.0273.97.N) and the Research Council of the KU Leuven (project nr OT-98-31) provided financial support, and Medtronic Inc, QUEST program (L1170) provided the stimulating devices. 1
2
3
4
Lippitz BE, Mindus P, Meyerson BA, Kihlström L, Lindquist Ch. Lesion topography and outcome after thermocapsulotomy and gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere. Neurosurgery 1999; 44: 452–60. Cosyns P, Caemaert J, Haaijman W, et al. Functional stereotactic neurosurgery for psychiatric disorders: an experience in Belgium and The Netherlands. Adv Tech Stand Neurosurg 1994; 21: 239–79. Meyerson BA. Neurosurgical treatment of mental disorders. Introduction and indications. In: Gildenberg PL, Tasker RR, eds. Textbook of stereotactic and functional neurosurgery. New York: McGraw-Hill; 1998: 1955–64. McNair DM, Lorr M, Droppleman LF, eds. Manual of the profile of Mood States. San Diego, CA: Educational and Industrial Testing Service, 1971.
Department of Neurosurgery/Laboratory of Experimental Neurosurgery and Neuroanatomy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium (B Nuttin MD, H Demeulemeester PhD, J Gybels MD); Department of Psychiatry, Universitaire Instelling Antwerpen, Belgium (P Cosyns MD); and Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institute/Hospital, Stockholm, Sweden (B Meyerson MD ) Correspondence to: Dr Bart J Nuttin (e-mail: [email protected])
Separating in-utero and postnatal influences on later disease David Gunnell, George Davey Smith, Alex McConnachie, Rosemary Greenwood, Mark Upton, Stephen Frankel Associations of birthweight with leg length and trunk length are similar. Childhood exposures rather than in-utero programming may underlie specific associations seen between leg length and mortality.
In-utero programming of the body’s structure and metabolism plays an important role in influencing the risk of adult chronic disease.1 It is argued that programming may occur in early development and, by implication, exposures operating in childhood are of less importance.1 The alternative life-course model of adult chronic disease development proposes that exposures acting throughout both early and later life are important in influencing later disease risk.2 Intrauterine programming and life-course models generate different predictions about the expected relative strength of associations between adult diseases and variables that act as proxies for fetal or childhood environments. Birthweight is often taken as a proxy for fetal nutrition. Leg length has been used as a proxy for childhood nutrition as it is the component of stature most sensitive to the childhood environment.3 Associations between
THE LANCET • Vol 354 • October 30, 1999
Amiral J, Marfaing KA, Wolf M, et al. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood 1996; 88: 410–16.
Blutbank, Charité Campus Virchow-Klinikum, D-13353 Berlin, Germany (O Meyer MD, Prof A Salama MD); and DiaMed AG, Cressier sur Morat, Switzerland (N Pittet MD, P Schwind PhD) Correspondence to: Dr O Meyer (e-mail: [email protected])
Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder Bart Nuttin, Paul Cosyns, Hilde Demeulemeester, Jan Gybels, Björn Meyerson Chronic electrical stimulation instead of bilateral capsulotomy was done in four selected patients with long-standing treatment-resistant obsessive-compulsive disorder. In three of them beneficial effects were observed.
Stereotactic interventions creating bilateral lesions in specific regions of the brain may be beneficial for some patients with long-standing treatment-resistant obsessive-compulsive disorder (OCD). Such lesions are irreversible; we explored the possibility of replacing this approach by chronic electrical stimulation via implanted electrodes. In four patients with severe OCD, quadripolar electrodes were stereotactically implanted in the anterior limbs of the internal capsules, one on each side. The selected stimulation targets were identical to those aimed for in capsulotomy. 1 Patient selection criteria were met. 2,3 The study protocol was approved by the local hospital ethics committees and was in accordance with the Helsinki Declaration of 1975 (revision 1983). In three patients, some beneficial effects were seen. One of them, a 39-year-old woman suffering from extremely severe OCD for more than 20 years, reported when stimulation was on, an almost instantaneous feeling of being relieved of anxiety and obsessive thinking, which disappeared after turning the stimulation off. She was continuously stimulated for 2 weeks and her parents reported that about 90% of her compulsive behaviour and rituals had vanished. In order to further assess the effects of stimulation, she was exposed to a structured test situation according to a double-blind protocol. Stimulation was applied with 100 Hz, a pulse width of 210 ms and all four contacts of the Model 3887 Pisces Quad Compact electrode (Medtronic Inc, Minneapolis) serving as cathode and the stimulator case as anode. The stimulator was set on (n=4, amplitude 4.7V) or off (n=4) in random order. The patient could not tell whether the stimulator was on or off. Thereafter the stimulator was set on (n=2, amplitude 5V) or off (n=2) in random order. The latter amplitude caused a headache, which disappeared after 10 s. This sensation probably let the patient know that the stimulator was on during these test sessions. During each of the 12 test sessions the same two standardised psychological tests were performed, in the same order (Profile of Mood States [POMS]4 and BourdonWiersma). A double-blind clinical assessment of the patient was made by six independent psychiatric residents with a video recording of the six stimulation-on and six stimulationoff sessions in random order. They were asked to rate relevant items from 0 (not present) to 3 (clearly present) for each of the 12 sessions. None of the results from the first eight test sessions were different from those of the last four
1526
test sessions. Ratings increased for the desirable symptoms social contact, communication, flow of ideas, assertiveness and mobility (the median scores for all of these items were 1 in stimulation-off versus 2 in stimulation-on). Ratings for doubt (median scores 2 in off, 1 in on) decreased during stimulation (p<0·05, Mann Whitney U test and Kendall’s coefficient of concordance). The vigour scale of the POMS increased during stimulation (mean scores: 1·67 in off vs 6·50 in on). Sustained attention assessed by the BourdonWiersma test did not change. These observations indicate that acute capsular stimulation can induce relevant beneficial effects in OCD and suggest that long-term stimulation may be useful in the management of treatment-resistant forms of this disease. Dedicated to the late Prof Per Mindus. We thank S Andréewitch, F Gielen, C Vankerckhoven, R Cluydts, L Gabriels, and K Martens for collaboration; K Mullet and B Linderoth for the fruitful discussions, P De Sutter for technical assistance, and C Plets for support. FWO (project nr G.0273.97.N) and the Research Council of the KU Leuven (project nr OT-98-31) provided financial support, and Medtronic Inc, QUEST program (L1170) provided the stimulating devices. 1
2
3
4
Lippitz BE, Mindus P, Meyerson BA, Kihlström L, Lindquist Ch. Lesion topography and outcome after thermocapsulotomy and gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere. Neurosurgery 1999; 44: 452–60. Cosyns P, Caemaert J, Haaijman W, et al. Functional stereotactic neurosurgery for psychiatric disorders: an experience in Belgium and The Netherlands. Adv Tech Stand Neurosurg 1994; 21: 239–79. Meyerson BA. Neurosurgical treatment of mental disorders. Introduction and indications. In: Gildenberg PL, Tasker RR, eds. Textbook of stereotactic and functional neurosurgery. New York: McGraw-Hill; 1998: 1955–64. McNair DM, Lorr M, Droppleman LF, eds. Manual of the profile of Mood States. San Diego, CA: Educational and Industrial Testing Service, 1971.
Department of Neurosurgery/Laboratory of Experimental Neurosurgery and Neuroanatomy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium (B Nuttin MD, H Demeulemeester PhD, J Gybels MD); Department of Psychiatry, Universitaire Instelling Antwerpen, Belgium (P Cosyns MD); and Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institute/Hospital, Stockholm, Sweden (B Meyerson MD ) Correspondence to: Dr Bart J Nuttin (e-mail: [email protected])
Separating in-utero and postnatal influences on later disease David Gunnell, George Davey Smith, Alex McConnachie, Rosemary Greenwood, Mark Upton, Stephen Frankel Associations of birthweight with leg length and trunk length are similar. Childhood exposures rather than in-utero programming may underlie specific associations seen between leg length and mortality.
In-utero programming of the body’s structure and metabolism plays an important role in influencing the risk of adult chronic disease.1 It is argued that programming may occur in early development and, by implication, exposures operating in childhood are of less importance.1 The alternative life-course model of adult chronic disease development proposes that exposures acting throughout both early and later life are important in influencing later disease risk.2 Intrauterine programming and life-course models generate different predictions about the expected relative strength of associations between adult diseases and variables that act as proxies for fetal or childhood environments. Birthweight is often taken as a proxy for fetal nutrition. Leg length has been used as a proxy for childhood nutrition as it is the component of stature most sensitive to the childhood environment.3 Associations between
THE LANCET • Vol 354 • October 30, 1999