Peer-Review Reports
Deep Brain Stimulation of the Nucleus Accumbens and Bed Nucleus of Stria Terminalis for Obsessive-Compulsive Disorder: A Case Series Lucrezia Islam1, Angelo Franzini2, Giuseppe Messina2, Silvio Scarone1, Orsola Gambini1
Key words Bed nucleus stria terminalis - Deep brain stimulation - Nucleus accumbens - Obsessive-compulsive disorder -
Abbreviations and Acronyms BNST: Bed nucleus of stria terminalis CBT: Cognitive behavioral therapy DBS: Deep brain stimulation DSM: Diagnostic and Statistical Manual of Mental Disorders ECT: Electroconvulsive therapy GAF: Global Assessment of Functioning HAM-D: Hamilton Depression Rating Scale NACC: Nucleus accumbens OCD: Obsessiveecompulsive disorder SSRIs: Selective-serotonin reuptake inhibitors Y-BOCS: Yale Brown Obsessive-Compulsive Scale From the 1Department of Psychiatry, University of Milan Medical School, Ospedale San Paolo; and 2Department of Neurosurgery, Istituto Neurologico Carlo Besta, Milan, Italy
- BACKGROUND:
Obsessive-compulsive disorder (OCD) is a psychiatric condition defined by the presence of obsessions, compulsions, or both. It has a lifetime prevalence of 2%e3% and causes significant impairment in social and work functioning, as well as a reduced quality of life. Treatment includes pharmacotherapy and psychotherapy, but a significant number of patients fail to respond to treatment. Deep brain stimulation has shown to be a safe and effective procedure for severe, chronic, treatment-resistant OCD, and several surgical targets have been proposed for treatment, including the nucleus accumbens, the anterior limb of the internal capsule, the subthalamic nucleus, the globus pallidus, and the bed nucleus of stria terminalis.
- OBJECTIVES:
To report the first Italian case series of patients who underwent DBS of 2 distinct targets for OCD: nulceus accumbens and bed nulceus of stria terminalis. METHODS: Four patients underwent DBS of the nulceus accumbens, and 4 patients underwent DBS of the bed nucleus of stria terminalis.
- RESULTS:
Six patients showed a significant improvement in OCD symptoms. CONCLUSIONS: DBS of these 2 structures is a safe and effective procedure for the treatment of severe, refractory OCD.
To whom correspondence should be addressed: Dr. Lucrezia Islam, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2014.12.024 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION Obsessive-Compulsive Disorder (OCD) OCD is defined by the presence of obsessions, compulsions, or both. Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate; compulsions are repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly (2). OCD was classified as an anxiety disorder in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM); the DSM-V has included a new chapter on obsessive-compulsive spectrum disorders, reflecting the fact that OCD is a separate category from
anxiety disorders and forms a spectrum together with hoarding disorder, trichotillomania, and other OCD-related disorders. Compared with other psychiatric conditions, such as affective or psychotic disorders, OCD may appear in full-blown form early in life. It has a lifetime and 12-month prevalence estimates of approximately 2.3% and 1.2% respectively (13, 19, 37), and causes significant impairment in work and social functioning, as well as reduced quality of life, making it a significant cause of disability (15, 25). Although some patients may present acute or episodic OCD, it is usually a chronic disorder: patients with chronic OCD may experience periods of exacerbation and remission or progressive worsening over time with deterioration of global functioning. First-line treatments include cognitive behavioral therapy (CBT) with fear exposure and response prevention (1, 11, 33, 35), as well as pharmacotherapy, namely selective serotonin-reuptake inhibitors (SSRIs). Patients who have not responded to at least 2 adequate trials of first-line medications
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
may benefit from clomipramine or from an augmentation strategy, that is, lithium, clonazepam, atypical antipsychotics, or electroconvulsive therapy (ECT) (5, 7, 9, 38). A combination of pharmacotherapy and CBT is often used (10, 14). It is a well-accepted fact that many patients with OCD do not respond to traditional medication or CBT. Different factors may influence response to treatment: for instance, symptoms such as hoarding compulsions, and obsessions focused on sexual or religious themes, are predictive of poorer outcome. Severity of illness, as measured with the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), is also related to poor treatment response, as is the copresence of depressive or anxiety symptoms (3, 20, 35, 42). Up to 10% of patients with OCD are considered to be treatment resistant, meaning that, despite appropriate treatment, they still display severe symptoms (3, 7, 21, 22). In pharmacologic trials, treatment resistance is defined as a failure to respond (a response is considered a decrease of 35% in Y-BOCS scale’s score) to 3 first-line medications
www.WORLDNEUROSURGERY.org
1
PEER-REVIEW REPORTS LUCREZIA ISLAM ET AL.
(SSRIs or clomipramine), 2 second-line medications (augmentation strategies), and at least 6 months of CBT. The neurobiological underpinnings of OCD include widespread abnormalities in the basal ganglia and frontal regions (32). Imaging studies suggest that in patients with OCD, there is abnormal metabolic activity in the orbitofrontal cortex, the anterior cingulate/caudal medial prefrontal cortex, and the caudate nucleus (34, 39, 43, 44). Deep Brain Stimulation Electrical stimulation of the brain was used to map cortical function in the 1930s (30), but it was only later that neurosurgeons began investigating the effects of stimulating deeper structures (17). Deep brain stimulation (DBS) originally was used for the treatment of movement disorders, namely essential tremor and Parkinson’s disease (31). Surgical treatment for psychiatric disorders (psychosurgery) has been used since the 1940s and includes lesional procedures such as capsulotomy (23, 27, 36), subcaudate tractotomy, and limbic leucotomy (a combination of subcaudate tractotomy and anterior cingulotomy) (18) for the treatment of OCD. In early 2009, the U.S. Food and Drug Administration granted limited humanitarian approval for DBS for otherwise-intractable OCD (18). Not all patients with OCD can be considered candidates for DBS. From a psychiatric standpoint, potential candidates have to satisfy the following conditions: chronicity (duration of illness, usually over 5 years), severity (usually cut-off is a Y-BOCS score of 28 or greater), and treatment resistance, as previously described. Careful screening of candidates is crucial. In this report we present a series of 8 patients who underwent DBS of different surgical targets for OCD between 2009 and 2014 at Istituto Neurologico “Carlo Besta” in Milan. PATIENTS AND METHODS Written informed consent was obtained from all patients for publication of this case series. Copies of the written consent and CARE checklist are available. Patients Potential candidates for DBS were referred to the outpatient OCD unit at Ospedale
2
www.SCIENCEDIRECT.com
DBS IN THE TREATMENT OF OCD
San Paolo, where they underwent psychiatric screening by their psychiatrists. DSM- IV-Text Revision diagnostic criteria were used for psychiatric diagnoses. Patients’ clinical charts were accurately evaluated at the screening visit. We acquired a detailed patient history, reviewed their clinical records, and personally contacted their psychiatrists to ensure that OCD was the primary diagnosis. The presence and severity of OCD symptoms were evaluated by means of Y-BOCS; severity of depressive symptoms was evaluated by means of Hamilton Depression Rating Scale (HAM-D), and the Y-BOCS checklist was used to investigate present and past OCD symptoms. Structured Clinical Interview for DSM-IV I and II were administered for diagnosing psychiatric disorders. Two patients also underwent evaluation with the ObsessiveCompulsive Self Rating Scale (lifetime and last month versions). Inclusion criteria were age (18 or older), severe, chronic, treatment-resistant OCD. Chronicity was defined as duration of illness of at least 5 years without remission. Severity was defined as a Y-BOCS score of 30/40 or greater. Treatment resistance was defined as an unsuccessful trial with maximum tolerated dose of at least 4 of clomipramine, fluvoxamine, sertraline, paroxetine, fluoxetine, citalopram, or escitalopram for at least 3 months, with augmentation strategies with at least 2 of lithium, clonazepam, atypical antipsychotics, ECT, and resistance to CBT. Exclusion criteria were younger than 18 years of age, a diagnosis of current or lifetime psychotic disorder, substance abuse disorder or personality disorder so severe that it may compromise compliance to DBS follow-up visits, a current clinically significant neurologic disorder or medical illness; mental retardation (an intelligence quotient
Deep Brain Stimulation of the Nucleus Accumbens and Bed Nucleus of Stria Terminalis for Obsessive-Compulsive Disorder: A Case Series Lucrezia Islam1, Angelo Franzini2, Giuseppe Messina2, Silvio Scarone1, Orsola Gambini1
Key words Bed nucleus stria terminalis - Deep brain stimulation - Nucleus accumbens - Obsessive-compulsive disorder -
Abbreviations and Acronyms BNST: Bed nucleus of stria terminalis CBT: Cognitive behavioral therapy DBS: Deep brain stimulation DSM: Diagnostic and Statistical Manual of Mental Disorders ECT: Electroconvulsive therapy GAF: Global Assessment of Functioning HAM-D: Hamilton Depression Rating Scale NACC: Nucleus accumbens OCD: Obsessiveecompulsive disorder SSRIs: Selective-serotonin reuptake inhibitors Y-BOCS: Yale Brown Obsessive-Compulsive Scale From the 1Department of Psychiatry, University of Milan Medical School, Ospedale San Paolo; and 2Department of Neurosurgery, Istituto Neurologico Carlo Besta, Milan, Italy
- BACKGROUND:
Obsessive-compulsive disorder (OCD) is a psychiatric condition defined by the presence of obsessions, compulsions, or both. It has a lifetime prevalence of 2%e3% and causes significant impairment in social and work functioning, as well as a reduced quality of life. Treatment includes pharmacotherapy and psychotherapy, but a significant number of patients fail to respond to treatment. Deep brain stimulation has shown to be a safe and effective procedure for severe, chronic, treatment-resistant OCD, and several surgical targets have been proposed for treatment, including the nucleus accumbens, the anterior limb of the internal capsule, the subthalamic nucleus, the globus pallidus, and the bed nucleus of stria terminalis.
- OBJECTIVES:
To report the first Italian case series of patients who underwent DBS of 2 distinct targets for OCD: nulceus accumbens and bed nulceus of stria terminalis. METHODS: Four patients underwent DBS of the nulceus accumbens, and 4 patients underwent DBS of the bed nucleus of stria terminalis.
- RESULTS:
Six patients showed a significant improvement in OCD symptoms. CONCLUSIONS: DBS of these 2 structures is a safe and effective procedure for the treatment of severe, refractory OCD.
To whom correspondence should be addressed: Dr. Lucrezia Islam, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2014.12.024 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION Obsessive-Compulsive Disorder (OCD) OCD is defined by the presence of obsessions, compulsions, or both. Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate; compulsions are repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly (2). OCD was classified as an anxiety disorder in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM); the DSM-V has included a new chapter on obsessive-compulsive spectrum disorders, reflecting the fact that OCD is a separate category from
anxiety disorders and forms a spectrum together with hoarding disorder, trichotillomania, and other OCD-related disorders. Compared with other psychiatric conditions, such as affective or psychotic disorders, OCD may appear in full-blown form early in life. It has a lifetime and 12-month prevalence estimates of approximately 2.3% and 1.2% respectively (13, 19, 37), and causes significant impairment in work and social functioning, as well as reduced quality of life, making it a significant cause of disability (15, 25). Although some patients may present acute or episodic OCD, it is usually a chronic disorder: patients with chronic OCD may experience periods of exacerbation and remission or progressive worsening over time with deterioration of global functioning. First-line treatments include cognitive behavioral therapy (CBT) with fear exposure and response prevention (1, 11, 33, 35), as well as pharmacotherapy, namely selective serotonin-reuptake inhibitors (SSRIs). Patients who have not responded to at least 2 adequate trials of first-line medications
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
may benefit from clomipramine or from an augmentation strategy, that is, lithium, clonazepam, atypical antipsychotics, or electroconvulsive therapy (ECT) (5, 7, 9, 38). A combination of pharmacotherapy and CBT is often used (10, 14). It is a well-accepted fact that many patients with OCD do not respond to traditional medication or CBT. Different factors may influence response to treatment: for instance, symptoms such as hoarding compulsions, and obsessions focused on sexual or religious themes, are predictive of poorer outcome. Severity of illness, as measured with the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), is also related to poor treatment response, as is the copresence of depressive or anxiety symptoms (3, 20, 35, 42). Up to 10% of patients with OCD are considered to be treatment resistant, meaning that, despite appropriate treatment, they still display severe symptoms (3, 7, 21, 22). In pharmacologic trials, treatment resistance is defined as a failure to respond (a response is considered a decrease of 35% in Y-BOCS scale’s score) to 3 first-line medications
www.WORLDNEUROSURGERY.org
1
PEER-REVIEW REPORTS LUCREZIA ISLAM ET AL.
(SSRIs or clomipramine), 2 second-line medications (augmentation strategies), and at least 6 months of CBT. The neurobiological underpinnings of OCD include widespread abnormalities in the basal ganglia and frontal regions (32). Imaging studies suggest that in patients with OCD, there is abnormal metabolic activity in the orbitofrontal cortex, the anterior cingulate/caudal medial prefrontal cortex, and the caudate nucleus (34, 39, 43, 44). Deep Brain Stimulation Electrical stimulation of the brain was used to map cortical function in the 1930s (30), but it was only later that neurosurgeons began investigating the effects of stimulating deeper structures (17). Deep brain stimulation (DBS) originally was used for the treatment of movement disorders, namely essential tremor and Parkinson’s disease (31). Surgical treatment for psychiatric disorders (psychosurgery) has been used since the 1940s and includes lesional procedures such as capsulotomy (23, 27, 36), subcaudate tractotomy, and limbic leucotomy (a combination of subcaudate tractotomy and anterior cingulotomy) (18) for the treatment of OCD. In early 2009, the U.S. Food and Drug Administration granted limited humanitarian approval for DBS for otherwise-intractable OCD (18). Not all patients with OCD can be considered candidates for DBS. From a psychiatric standpoint, potential candidates have to satisfy the following conditions: chronicity (duration of illness, usually over 5 years), severity (usually cut-off is a Y-BOCS score of 28 or greater), and treatment resistance, as previously described. Careful screening of candidates is crucial. In this report we present a series of 8 patients who underwent DBS of different surgical targets for OCD between 2009 and 2014 at Istituto Neurologico “Carlo Besta” in Milan. PATIENTS AND METHODS Written informed consent was obtained from all patients for publication of this case series. Copies of the written consent and CARE checklist are available. Patients Potential candidates for DBS were referred to the outpatient OCD unit at Ospedale
2
www.SCIENCEDIRECT.com
DBS IN THE TREATMENT OF OCD
San Paolo, where they underwent psychiatric screening by their psychiatrists. DSM- IV-Text Revision diagnostic criteria were used for psychiatric diagnoses. Patients’ clinical charts were accurately evaluated at the screening visit. We acquired a detailed patient history, reviewed their clinical records, and personally contacted their psychiatrists to ensure that OCD was the primary diagnosis. The presence and severity of OCD symptoms were evaluated by means of Y-BOCS; severity of depressive symptoms was evaluated by means of Hamilton Depression Rating Scale (HAM-D), and the Y-BOCS checklist was used to investigate present and past OCD symptoms. Structured Clinical Interview for DSM-IV I and II were administered for diagnosing psychiatric disorders. Two patients also underwent evaluation with the ObsessiveCompulsive Self Rating Scale (lifetime and last month versions). Inclusion criteria were age (18 or older), severe, chronic, treatment-resistant OCD. Chronicity was defined as duration of illness of at least 5 years without remission. Severity was defined as a Y-BOCS score of 30/40 or greater. Treatment resistance was defined as an unsuccessful trial with maximum tolerated dose of at least 4 of clomipramine, fluvoxamine, sertraline, paroxetine, fluoxetine, citalopram, or escitalopram for at least 3 months, with augmentation strategies with at least 2 of lithium, clonazepam, atypical antipsychotics, ECT, and resistance to CBT. Exclusion criteria were younger than 18 years of age, a diagnosis of current or lifetime psychotic disorder, substance abuse disorder or personality disorder so severe that it may compromise compliance to DBS follow-up visits, a current clinically significant neurologic disorder or medical illness; mental retardation (an intelligence quotient
