Neurosurgical treatment of severe obsessive‐compulsive disorder associated with Tourette's syndrome

Kurlan, Roger; Kersun, Jonathan M.; Ht, Ballantine; Ed, Caine

doi:10.1002/mds.870050211

Cited by 55 publications

(23 citation statements)

References 14 publications

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“…7,8 Although the molecular causes of these genetic and/or autoimmune neurological syndromes remain undetermined, the high comorbidity of OCD and TS implies a shared or overlapping neuronal basis, 4,5,9 one associated with either hyperactivity/ hyper-responsiveness or lack of inhibition of cortical orbitofrontal, somatosensory-sensorimotor and amygdalar regions and their efferent striatal circuits. [10][11][12][13][14][15] Exactly which neurons in these regions actually evoke TS+OCD symptoms is also unknown. However, cortical glutamatergic output neurons are known to coexpress dopamine D1 and serotonin 5-HT2 receptors, while their presynaptic cortical inhibitory interneurons and postsynaptic striatal neurons express dopamine D2 receptors, [16][17][18] possibly accounting for the therapeutic effects of manipulating these three neurotransmitters.…”

Section: Introductionmentioning

confidence: 99%

“…However, cortical glutamatergic output neurons are known to coexpress dopamine D1 and serotonin 5-HT2 receptors, while their presynaptic cortical inhibitory interneurons and postsynaptic striatal neurons express dopamine D2 receptors, [16][17][18] possibly accounting for the therapeutic effects of manipulating these three neurotransmitters. 10,19 Animal models of cortical-limbic hyperactivityinduced OCD-like or TS-like behavior may be useful to predict the specific neuronal circuitry of such dis-orders, as well as to screen new potential therapeutic drugs for TS, OCD and TTM. We recently created such a model of OCD-like compulsive symptoms, the D1CT-7 transgenic mice, 20 using a neuropotentiating transgene that expresses the cAMP-elevating, stimulusevoked neurotransmission-increasing intracellular A1 subunit of cholera toxin 21 in only two small subsets of neurons in the adult CNS.…”

Section: Introductionmentioning

confidence: 99%

“…We discuss how the CGN model of TS+OCD circuitry is consistent with the standard model of parallel cortico-striatalthalamo-cortical circuits, 26 and incorporates older disparate glutamate, dopamine, norepinephrine and serotonin 'neurotransmitter' models of TS and OCD. 2,10,15,27,28 We discuss how the CGN hyperactivity model of TS+OCD is consistent with recent transcranial magnetic stimulation (TMS) studies showing cortical hyperactivity, hyper-responsiveness or lack of inhibition in both TS and OCD, 13,14 and is also supported by three recent clinical neuroimaging studies: Magnetic resonance spectroscopy (MRS) showing increased striatal excitatory glutamate deposition in OCD and its normalization after drug therapy; 15 positron emission tomography (PET) showing increased striatal inhibitory D2 receptor activity in TS; 29 and functional magnetic resonance imaging (fMRI) showing decreased striatal responsiveness in TS. 30 Finally, we discuss how comorbid TS, OCD and ADD/ADHD symptoms may be explained by a spectrum between hyperactivity and inactivity of cortical-limbic glutamatergic neurons.…”

Section: Introductionmentioning

confidence: 99%

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A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry

2002

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The tic disorder Tourette's Syndrome (TS) and obsessive-compulsive disorder (OCD) are comorbid behavioral disorders, suggesting a shared but still unknown neuronal basis. To 'circuit-test' such behaviors, we previously engineered transgenic mice expressing a neuropotentiating protein (cholera toxin A1 subunit) within a cortical-limbic subset of dopamine D1-receptor expressing (D1+) neurons known to trigger glutamatergic excitation of orbitofrontal, sensorimotor, limbic and efferent striatal circuits thought to be hyperactive or affected in OCD and TS. These mice exhibited OCD-like behaviors including generalized behavioral perseveration and compulsion-like leaping and grooming-associated pulling and biting of skin and hair. We now report that these OCD-like mice, like humans, also exhibit comorbid TS-like behaviors, including juvenile-onset tics; increased tic number, complexity and flurries; increased tic severity in males; voluntary tic suppression; and tic responsiveness to a non-cataleptic TS+OCD drug therapy (clonidine, 0.01 mg kg −1 ). These data suggest that hormonal gender differences, apart from the influence of genetic or autoimmune etiologic factors, may be sufficient to aggravate tic severity in human TS males compared to TS females. These data also proffer a precise neuronal basis for TS+OCD, wherein tics and primary compulsions or obsessions are evoked by hyperactivity of various cortical-limbic projection neurons' glutamatergic output to efferent targets like the striatum. The 'Cortical-limbic Glutamatergic Neuron' (CGN) neuronal circuit model merges formerly opposed neurotransmitter models of TS and OCD, and is consistent with new clinical reports of increased cortical hyperactivity, striatal glutamate and striatal inhibitory D2 receptors, and reduced striatal responsiveness, in these disorders.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry

2002

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“…The possible neuroanatomical basis of the episodic perseverance or repetition of any and all behaviors in D1CT-7 mice is not known, but we predict that, like their biting during grooming and their leaping, it could be a consequence of neurostimulation of regions also hyperactive in OCD, including the amygdala and somatosensory/insular and orbitofrontal (OFC) cortical regions (Horwitz et al, 1991;Breiter et al, 1996) that in OCD are similarly thought to hyperstimulate the striatum glutamatergically (Bernstein et al, 1975;Kurlan et al, 1990;Breiter et al, 1996). The potentiated amygdalar, somatosensory/insular, and piriform D1ϩ neurons of D1CT-7 mice are thought to excite directly or indirectly not only deep-layer striatally projecting cortical neurons and the striatum but also the OFC among other prefrontal regions (McDonald, 1987;Morecraft et al, 1992;Barbas, 1993).…”

Section: Putative Neuroanatomical Basis For D1ct Mice Compulsive Abnomentioning

confidence: 99%

OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons

et al. 1999

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To study the behavioral role of neurons containing the D1 dopamine receptor (D1ϩ), we have used a genetic neurostimulatory approach. We generated transgenic mice that express an intracellular form of cholera toxin (CT), a neuropotentiating enzyme that chronically activates stimulatory G-protein (G s ) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNSexpressed promoters, confers transgene expression that is regionally restricted to different D1ϩ CNS subsets in different transgenic lines, we observed distinct but related psychomotor disorders in different D1CT-expressing founders. In a D1CT line in which transgene expression was restricted to the following D1ϩ CNS regions-the piriform cortex layer II, layers II-III of somatosensory cortical areas, and the intercalated nucleus of the amygdala-D1CT mice showed normal CNS and D1ϩ neural architecture but increased cAMP content in whole extracts of the piriform and somatosensory cortex. These mice also exhibited a constellation of compulsive behavioral abnormalities that strongly resembled human cortical-limbic-induced compulsive disorders such as obsessive-compulsive disorder (OCD). These compulsive behaviors included episodes of perseverance or repetition of any and all normal behaviors, repetitive nonaggressive biting of siblings during grooming, and repetitive leaping. These results suggest that chronic potentiation of cortical and limbic D1ϩ neurons thought to induce glutamatergic output to the striatum causes behaviors reminiscent of those in human cortical-limbic-induced compulsive disorders.

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“…Kurlan et al [79] reported 2 patients suffering from medically refractory OCDs associated with Tourette's syndrome. They performed bilateral radiofrequency cingulomotomies under pneumoencephalographic guidance utilizing the operative technique described by Ballantine et al [66] .…”

Section: Psychiatric Disordersmentioning

confidence: 99%

Historic Evolution of Open Cingulectomy and Stereotactic Cingulotomy in the Management of Medically Intractable Psychiatric Disorders, Pain and Drug Addiction

Brotis¹,

Kapsalaki

Paterakis³

et al. 2009

Stereotact Funct Neurosurg

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Stereotactic cingulotomy constitutes a psychosurgical procedure nowadays advocated in the treatment of medically intractable obsessive-compulsive disorder, chronic pain and drug addiction. From its theoretical conception to the first cingulectomies performed and modern stereotactic-guided cingulotomies, various target localization methods, different surgical techniques, and numerous lesioning devices have been utilized. In the current article, the authors performed a literature review related to cingular lesion placement in an effort to identify misconceptions of the past, recapitulate existing knowledge and recognize targets for further research. The initial animal and human electrophysiologic experimental data regarding the role of the cingulate cortex in various behavioral and cognitive functions were meticulously reviewed. The clinical indications, surgical technique and the clinical results and complications of open cingulectomies were examined. The anatomic target localization methodologies, surgical technique, and the outcome of the initial stereotactic cingulotomy procedures were reviewed, and the evolution of the imaging techniques, stereotactic devices, and lesioning strategies were followed. The modern advanced surgical techniques, clinical outcome and the procedure-associated complications were analyzed with particular emphasis on the emotional, behavioral, and cognitive procedure-induced changes. Large-scale prospective studies with strict inclusion and well-defined, objective outcome criteria are necessary for defining the role of stereotactic cingulotomy in the current psychosurgical armamentarium.

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Neurosurgical treatment of severe obsessive‐compulsive disorder associated with Tourette's syndrome

Cited by 55 publications

References 14 publications

A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry

A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry

OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons

Historic Evolution of Open Cingulectomy and Stereotactic Cingulotomy in the Management of Medically Intractable Psychiatric Disorders, Pain and Drug Addiction

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