DBS for Treatment-Refractory Obsessive Compulsive Disorder
DBS for Treatment-Refractory Obsessive Compulsive Disorder
The ALIC is the part of the Internal Capsule that lies anterior to the genu, located between the head of the caudate nucleus and the lenticular nucleus. Its fibers connect the prefrontal cortex and the subcortical nuclei, specifically the dorsomedial thalamus. Outcomes of anterior capsulotomy for refractory OCD led to the selection of the ALIC as a target for DBS.
Nuttin and colleagues (1999) were the first to replace lesioning by high frequency DBS in OCD patients. They reported beneficial effects after bilateral stimulation of the ALIC in three out of four OCD patients. However, this evaluation is based on clinical observation only; no quantitative data have been reported.
In 2003, Nuttin et al. improved on the assessment procedure and made use of a blinded crossover design with alternating stimulation on/off-periods of 3 months with four OCD patients. The Y-BOCS scores were significantly lower at the end of the active stimulation compared to sham stimulation (placebo) (19.8 ± 8.0 vs. 32.3 ± 3.9). In an addendum to the main text, information on four additional patients is provided. Y-BOCS reductions are above 35% for four out of six patients. One patient, for whom DBS did not proof effective, received capsulotomy. For the other two patients only an anecdotal report is available.
The same group reported three cases of OCD patients receiving DBS of the ALIC, one of them was already included in Nuttin et al.'s study. In one case, electrodes were removed 15 months after implantation, for the remaining two patients Y-BOCS scores dropped 12 and 23 points from baseline. The latest follow up was 33 and 39 months after surgery.
A single case of ALIC DBS was reported by Anderson and Ahmed in 2003. The latest follow-up was performed three months after surgery, so that the Y-BOCS reduction of 79.4% (from 34 to 7 points) needs to be regarded with caution.
Y-BOCS scores of four patients undergoing bilateral ALIC stimulation were assessed in a short-term, blinded, on-off design with four consecutive 3 week periods, as well as in an unblinded, long-term follow up ranging from 4 to 23 months (Abelson et al.,). The first design revealed mixed results, with two patients reporting lower mean Y-BOCS scores in the off-condition, compared to the on-condition (on vs. off: 37.5 vs. 39, 31.5 vs. 29, 10 vs. 23, 27 vs. 26, respectively). In the latter design two of the four patients could be classified as responders, showing a 44% and 73% reduction from baseline, respectively. The other two patients showed a 0% and 4% reduction, respectively.
Servello et al. reported thalamic DBS in four patients with Tourette syndrome and comorbid OCD. Case one did not show significant improvement in Y-BOCS scores 30 months after DBS with scores remaining around the baseline level of 23 points. Also an additional surgery to implant rescue leads into ALIC/NAc region did not result in a significant symptom reduction. The latest follow-up was performed 44 months after the first surgery. Also the second patient received a "rescue surgery" ten months after electrode implantation. In the 20 months follow-up period Y-BOCS scores improved only mildly with a drop by 13 points from baseline at 18 months post-surgery (from 38 to 25) representing the biggest symptom reduction. Case three improved progressively from a Y-BOCS score of 38 pre-surgery to 15 at the 19 months follow up. The fourth patient displayed a similar improvement (16 vs. 35) in a period of 10 months (see Table 1).
As a component of the ventral striatum, the NAc is located beneath the ALIC, at the junction between the head of the caudate and the anterior portion of the putamen. Due to the spatial proximity of NAc and ALIC it is possible to stimulate both target structures. By placing the tip of the electrode in the NAc the deepest contact will stimulate the ventral striatal region, whereas the most dorsal contact, towards the top of the electrode might affect also the ALIC. The NAc, the main gate structure of the basal ganglia is considered to be a motor-limbic interface associated with reward processing, which makes it a promising target structure for many psychiatric disorders and OCD in particular, since a dysfunction in the reward system, i.e. the hyperactivity between NAc and prefrontal cortex, may be an underlying cause for the disorder.
In 2003, Sturm et al. conducted a pilot study with four patients suffering from anxiety and OCD. Authors report total recovery from anxiety- and OCD-symptoms in all but one patient, but no Y-BOCS scores have been reported, therefore an investigator bias cannot be excluded. Based on these findings, a larger, methodologically improved study (including a brief double blind crossover phase) was conducted. The results of this study published in 2010, put the previous, overly positive results in perspective. In this study conducted by Huff et al. ten patients received stimulation but unilateral to the right NAc. Five patients were classified as partial responders (i.e., a minimal symptom reduction 25%) and one patient as a full responder (i.e., a minimal symptom reduction of 35%). Mean Y-BOCS scores indicated a significant decrease of OCD symptoms after 12 months of active stimulation (from 32.2 ± 4.0 to 25.4 ± 6.7).
A single case of DBS targeting the ventral caudate nucleus in a patient suffering from severe OCD and concomitant major depression was published by Aouizerate et al.. The baseline Y-BOCS score of 25 did not change significantly in the first 9 months of stimulation, but decreased dramatically to 10 and 14 points 12 and 15 months after surgery.
Plewnia et al. reported on the single case of a woman suffering from OCD, as well as residual symptoms of schizophrenia, who received DBS of the right NAc. Y-BOCS scores improved from 32 points one month prior to surgery to 24 four weeks after treatment onset and remained at this level for the two year follow up period.
Denys and colleagues published data on 16 OCD patients with DBS of the NAc. After eight months open phase, Y-BOCS scores decreased by 46%. Nine of the patients were classified as responders. Following the open phase period the authors conducted a double-blind two week cross-over design, of active or sham stimulation, which underlined the positive treatment effects. It is noteworthy that in this study an additional treatment of cognitive behavioral therapy (CBT) was offered once a substantial decrease in Y-BOCS scores (six points on average) was achieved by DBS. In accordance with the therapy refractoriness criteria, CBT was not effective prior to surgery. However, in combination with DBS a substantial improvement in CBT efficacy was reported. This may indicate that DBS creates the necessary readiness of the brain to implement elements of CBT.
Franzini et al. describe two cases of NAc DBS in OCD patients. Patient one was additionally diagnosed with comorbid bipolar disorder type I. His Y-BOCS scores improved from 38 to 22 at the 24 months follow-up. Patient two was diagnosed with comorbid body dysmorphic disorder, phobic anxiety disorder and depressive disorder, 27 months after surgery he showed a 10 point decrease (from 30 to 20) in Y-BOCS scores.
Roh et al. described a further DBS study targeting the NAc with the proximal contact extending into part of the caudate nucleus and the IC in four OCD patients. After 24 months of treatment, baseline Y-BOCS scores decreased from an average 37.0 ± 1.8 to 14.8 ± 5.0, corresponding to an improvement rate of 59.7 ± 14.6%.
Barcia et al. used the possibility of intra-individual comparison between two stimulation targets (NAc and STN) in two patients. Different combinations of electrodes were activated for two days, followed by a one-day washout period. Bilateral stimulation of the NAc led to a decrease in Y-BOCS score from 33 to 20 for patient 1 and from 33 to 16 for patient 2. Stimulation of the left accumbens and left STN yielded the lowest Y-BOCS scores for both patients (patient 1: 16; patient 2: 12) (data for STN-DBS can be found under 3.4). Unfortunately, one has to be cautious to conjecture interpretations due to the very low number of subjects (see Table 2).
The ventral striatal (VS) area encompasses the ventral caudate nucleus and nucleus accumbens and is thought to be involved in motivation and reward. Combined with the ventral capsule (VC), it is referred to as the VC/VS region.
Greenberg et al. conducted a study with bilateral stimulation of the VC/VS in 10 OCD patients. They administered follow-ups at 1, 3, 6, 12, 18, 24, 30 and 36 months after surgery, the follow-up at 36 months did only capture 8 patients (one patient died 9 months after surgery, due to cancer and her data has not been included, and one patient dropped out after 24 months.) Y-BOCS scores improved from 34.6 ± 0.6 (mean ± SEM) pre-operatively to 25 ± 1.6 at 3 months and 22.3 ± 2.1 at 36 months.
In 2010 Greenberg et al. published results of 26 patients who underwent bilateral DBS of the VC/VS divided over four different research centers, including 10 patients they had previously reported. Follow-up periods in these studies ranged from 3 to 36 months, averaging 31.4 months. Y-BOCS scores improved from 34.0 ± 0.5 at baseline to 20.9 ± 2.4 at the latest follow-up, with this level of improvement being apparent already 3 months after active stimulation started (Y-BOCS 21.0 ± 1.8). Furthermore, the authors note that about 65% of the patients benefitted from the treatment due to clinically significant symptom reductions and functional improvement.
Six patients who received bilateral DBS of the VC/VS were assessed in a randomized, blinded, staggered onset design. After 12 months of active stimulation 67% (i.e. four out of six) patients were classified as responders (≥35% Y-BOCS score decrease from baseline). In fact, the mean baseline Y-BOCS score of 33.7 decreased by 15.67 ± 11.60 points (mean ± SD).
In another study targeting the VC/VS bilaterally, four OCD patients were assessed every 3 months for 15 months showing a 33.6% reduction (mean ± SD, 36.3 ± 2.1 pre-operatively vs. 24.3 ± 9.1 at 15 months).
In 2013 a single case report of a 51-Year old OCD patient who received DBS of the VC/VS was published. Her Y-BOCS scores fluctuated during the course of her 22-month follow-up, remaining somewhat stagnant over the first 9 months and then decreasing more dramatically to 10 points at 12 months follow-up. However, concomitant psychotherapy makes it difficult to attribute changes to DBS alone (see Table 3).
The STN is a component of the basal ganglia and is located ventral to the thalamus, dorsal to the substantia nigra, and medial to the corticospinal tract. Experiences with DBS in patients with Parkinson's disease (PD) and comorbid OCD symptoms have suggested the involvement of the STN in OCD.
Mallet et al. described a successful stimulation of the STN in two OCD patients with improvements of 58 and 64% (pre-operative Y-BOCS 26 and 23, respectively; Y-BOCS at 6 months follow-up 5 and 4, respectively). Fontaine et al. reported a second positive case: A 49-year-old man suffering from OCD as well as PD received bilateral stimulation of the STN, reducing Y-BOCS scores from a baseline of 32 to 1 after 6 months of active stimulation.
Six years after their first report on STN DBS in OCD, Mallet et al. published a study with a double-blind crossover design by which they assess the efficacy of bilateral STN stimulation. Sixteen OCD patients were randomly assigned to active stimulation followed by sham stimulation, or vice versa, with eight patients in each group. Assessment at the end of the two 3 months periods revealed a significantly lower Y-BOCS score for patients under active stimulation (mean ± SD, 19 ± 8) compared to patients under sham stimulation (28 ± 7).
Finally, Chabardès et al. described four patients, two of them originally reported by Mallet et al.. Of the remaining two, one showed a symptom reduction of 78% (8 vs. 29) while the second patient was classified as a partial responder with an improvement of about 34% (21 vs. 32) 6 months after electrode implantation. STN-DBS data of the study by Barcia et al. revealed the following improvement in Y-BOCS scores: scores of patient 1 decreased from 33 at baseline to 20 three months follow-up and of patient 2 decreased from 33 at baseline to 18 (see Table 4).
The ITP is the connecting structure between orbitofrontal cortex and thalamus and part of the orbitofrontal thalamic system. Its association with OCD symptoms makes it a promising target structure for DBS.
In 2009 Jiménez et al. reported bilateral ITP stimulation in five patients with refractory OCD. Y-BOCS scores were assessed every 3 months for a total of 12 months, showing a reduction of 51% at the last follow-up (mean ± SD, 17.8 ± 3.9 vs. 35 ± 6.2,).
Another study by Jiménez et al. assessed the efficacy of implantation of quadripolar deep brain stimulation electrodes in the ITP for six OCD patients. At 12 months follow-up a 51% decrease in Y-BOCS scores could be observed (mean ± SD, 17.5 ± 3.6 vs. 35.8 ± 5.9) which further decreased after 24 and 36 months (14.0 ± 7. 8 and 13.3 ± 5.7, respectively) (see Table 5).
Complications of DBS can be classified into 3 categories. First, 'procedure related adverse events' describe complications arising from the surgery itself. Second, difficulties may originate from the implantation device ('device related'). Third, the stimulation itself may cause effects on mood or cognition that can be acute and reversible or chronic in nature and are specific to the target region. Disorder related adverse events are not discussed at this point.
Procedure Related. Overall, six patients suffered from superficial wound infections following surgery and one patient exhibited an allergic reaction to the implantation device in the chest. Dell'Osso and colleagues described a patient who, following a minor inflammation at the area where the stimulator had been implanted, developed a scar-picking behavior, making it necessary to remove the device despite major improvements in OCD symptoms.
Serious adverse events during surgery included two seizures, and three intracerebral hemorrhages.
Device Related. In five patients breaks in stimulating leads or extension wires requiring replacement were reported. One patient reported dysesthesia in the subclavicular region that lasted for several weeks. Okun and colleagues reviewed symptoms potentially related to battery failure in 6 patients with refractory OCD, noting that suicidality, mood disturbance, panic attacks, fatigue, and a restless sensation in the extremities may be associated with battery failure. Nuttin et al., as well as Denys and colleagues reported on several patients who felt the leads or stimulation devices (5 permanent and 7 transient cases).
Stimulation Related. Anxiety: Twenty-five patients in four studies (three NAc studies, one VC/VS study) experienced an acute increase in anxiety. All of these were induced either by a change of stimulation parameters, or by battery depletion, so that anxiety symptoms were quickly resolved after parameter adaption or pacemaker exchange.
Mood: The most common effect on mood during chronic DBS was hypomania, experienced by 27 patients across five studies (two NAc studies and three VC/VS studies) -. In all cases mood elevation responded to parameter adjustment. One patient exhibited hypomania-like symptoms during initial DBS programming. Furthermore, Greenberg et al. reported irritability leading to domestic problems in one patient. Increased depression and suicidal thoughts were noted in six patients across three studies (one ALIC study, one NAc study, and one VC/VS study). It should be noted, however, that some of these patients reported similar episodes prior to surgery. One patient in the study by Abelson et al. whose symptoms were reduced after DBS, committed suicide one year after surgery and stated in a note that her suicide was unrelated to the study.
Cognition: Effects of DBS on cognition in patients suffering from OCD seem to occur only rarely. Some patients reported cognitive 'clouding' or diminished concentration in two studies. However, these were related only to certain parameter settings, and thus readily reversible. In the same study activation of the most dorsal contact during operation resulted in verbal perseveration in one patient. Three subjects in a study by Denys et al. reported words-finding difficulties. In eight patients across two studies DBS affected memory performance: one patient had brief flashbacks that recurred several times a day, which could be resolved with changing stimulation parameters, the memory problems in the other seven patients were transient and resolved over time.
Other. Next to these psychological effects some authors noted various other effects that may be attributed to DBS. These range from difficulties falling asleep over vertigo and weight loss or gain to long-lasting fatigue. Also an increased headache frequency and a single case of a visual disturbance in the left eye have been noted.
Results
Anterior Limb of Internal Capsule
The ALIC is the part of the Internal Capsule that lies anterior to the genu, located between the head of the caudate nucleus and the lenticular nucleus. Its fibers connect the prefrontal cortex and the subcortical nuclei, specifically the dorsomedial thalamus. Outcomes of anterior capsulotomy for refractory OCD led to the selection of the ALIC as a target for DBS.
Nuttin and colleagues (1999) were the first to replace lesioning by high frequency DBS in OCD patients. They reported beneficial effects after bilateral stimulation of the ALIC in three out of four OCD patients. However, this evaluation is based on clinical observation only; no quantitative data have been reported.
In 2003, Nuttin et al. improved on the assessment procedure and made use of a blinded crossover design with alternating stimulation on/off-periods of 3 months with four OCD patients. The Y-BOCS scores were significantly lower at the end of the active stimulation compared to sham stimulation (placebo) (19.8 ± 8.0 vs. 32.3 ± 3.9). In an addendum to the main text, information on four additional patients is provided. Y-BOCS reductions are above 35% for four out of six patients. One patient, for whom DBS did not proof effective, received capsulotomy. For the other two patients only an anecdotal report is available.
The same group reported three cases of OCD patients receiving DBS of the ALIC, one of them was already included in Nuttin et al.'s study. In one case, electrodes were removed 15 months after implantation, for the remaining two patients Y-BOCS scores dropped 12 and 23 points from baseline. The latest follow up was 33 and 39 months after surgery.
A single case of ALIC DBS was reported by Anderson and Ahmed in 2003. The latest follow-up was performed three months after surgery, so that the Y-BOCS reduction of 79.4% (from 34 to 7 points) needs to be regarded with caution.
Y-BOCS scores of four patients undergoing bilateral ALIC stimulation were assessed in a short-term, blinded, on-off design with four consecutive 3 week periods, as well as in an unblinded, long-term follow up ranging from 4 to 23 months (Abelson et al.,). The first design revealed mixed results, with two patients reporting lower mean Y-BOCS scores in the off-condition, compared to the on-condition (on vs. off: 37.5 vs. 39, 31.5 vs. 29, 10 vs. 23, 27 vs. 26, respectively). In the latter design two of the four patients could be classified as responders, showing a 44% and 73% reduction from baseline, respectively. The other two patients showed a 0% and 4% reduction, respectively.
Servello et al. reported thalamic DBS in four patients with Tourette syndrome and comorbid OCD. Case one did not show significant improvement in Y-BOCS scores 30 months after DBS with scores remaining around the baseline level of 23 points. Also an additional surgery to implant rescue leads into ALIC/NAc region did not result in a significant symptom reduction. The latest follow-up was performed 44 months after the first surgery. Also the second patient received a "rescue surgery" ten months after electrode implantation. In the 20 months follow-up period Y-BOCS scores improved only mildly with a drop by 13 points from baseline at 18 months post-surgery (from 38 to 25) representing the biggest symptom reduction. Case three improved progressively from a Y-BOCS score of 38 pre-surgery to 15 at the 19 months follow up. The fourth patient displayed a similar improvement (16 vs. 35) in a period of 10 months (see Table 1).
Nucleus Accumbens
As a component of the ventral striatum, the NAc is located beneath the ALIC, at the junction between the head of the caudate and the anterior portion of the putamen. Due to the spatial proximity of NAc and ALIC it is possible to stimulate both target structures. By placing the tip of the electrode in the NAc the deepest contact will stimulate the ventral striatal region, whereas the most dorsal contact, towards the top of the electrode might affect also the ALIC. The NAc, the main gate structure of the basal ganglia is considered to be a motor-limbic interface associated with reward processing, which makes it a promising target structure for many psychiatric disorders and OCD in particular, since a dysfunction in the reward system, i.e. the hyperactivity between NAc and prefrontal cortex, may be an underlying cause for the disorder.
In 2003, Sturm et al. conducted a pilot study with four patients suffering from anxiety and OCD. Authors report total recovery from anxiety- and OCD-symptoms in all but one patient, but no Y-BOCS scores have been reported, therefore an investigator bias cannot be excluded. Based on these findings, a larger, methodologically improved study (including a brief double blind crossover phase) was conducted. The results of this study published in 2010, put the previous, overly positive results in perspective. In this study conducted by Huff et al. ten patients received stimulation but unilateral to the right NAc. Five patients were classified as partial responders (i.e., a minimal symptom reduction 25%) and one patient as a full responder (i.e., a minimal symptom reduction of 35%). Mean Y-BOCS scores indicated a significant decrease of OCD symptoms after 12 months of active stimulation (from 32.2 ± 4.0 to 25.4 ± 6.7).
A single case of DBS targeting the ventral caudate nucleus in a patient suffering from severe OCD and concomitant major depression was published by Aouizerate et al.. The baseline Y-BOCS score of 25 did not change significantly in the first 9 months of stimulation, but decreased dramatically to 10 and 14 points 12 and 15 months after surgery.
Plewnia et al. reported on the single case of a woman suffering from OCD, as well as residual symptoms of schizophrenia, who received DBS of the right NAc. Y-BOCS scores improved from 32 points one month prior to surgery to 24 four weeks after treatment onset and remained at this level for the two year follow up period.
Denys and colleagues published data on 16 OCD patients with DBS of the NAc. After eight months open phase, Y-BOCS scores decreased by 46%. Nine of the patients were classified as responders. Following the open phase period the authors conducted a double-blind two week cross-over design, of active or sham stimulation, which underlined the positive treatment effects. It is noteworthy that in this study an additional treatment of cognitive behavioral therapy (CBT) was offered once a substantial decrease in Y-BOCS scores (six points on average) was achieved by DBS. In accordance with the therapy refractoriness criteria, CBT was not effective prior to surgery. However, in combination with DBS a substantial improvement in CBT efficacy was reported. This may indicate that DBS creates the necessary readiness of the brain to implement elements of CBT.
Franzini et al. describe two cases of NAc DBS in OCD patients. Patient one was additionally diagnosed with comorbid bipolar disorder type I. His Y-BOCS scores improved from 38 to 22 at the 24 months follow-up. Patient two was diagnosed with comorbid body dysmorphic disorder, phobic anxiety disorder and depressive disorder, 27 months after surgery he showed a 10 point decrease (from 30 to 20) in Y-BOCS scores.
Roh et al. described a further DBS study targeting the NAc with the proximal contact extending into part of the caudate nucleus and the IC in four OCD patients. After 24 months of treatment, baseline Y-BOCS scores decreased from an average 37.0 ± 1.8 to 14.8 ± 5.0, corresponding to an improvement rate of 59.7 ± 14.6%.
Barcia et al. used the possibility of intra-individual comparison between two stimulation targets (NAc and STN) in two patients. Different combinations of electrodes were activated for two days, followed by a one-day washout period. Bilateral stimulation of the NAc led to a decrease in Y-BOCS score from 33 to 20 for patient 1 and from 33 to 16 for patient 2. Stimulation of the left accumbens and left STN yielded the lowest Y-BOCS scores for both patients (patient 1: 16; patient 2: 12) (data for STN-DBS can be found under 3.4). Unfortunately, one has to be cautious to conjecture interpretations due to the very low number of subjects (see Table 2).
Ventral Capsule/Ventral Striatum (VC/VS)
The ventral striatal (VS) area encompasses the ventral caudate nucleus and nucleus accumbens and is thought to be involved in motivation and reward. Combined with the ventral capsule (VC), it is referred to as the VC/VS region.
Greenberg et al. conducted a study with bilateral stimulation of the VC/VS in 10 OCD patients. They administered follow-ups at 1, 3, 6, 12, 18, 24, 30 and 36 months after surgery, the follow-up at 36 months did only capture 8 patients (one patient died 9 months after surgery, due to cancer and her data has not been included, and one patient dropped out after 24 months.) Y-BOCS scores improved from 34.6 ± 0.6 (mean ± SEM) pre-operatively to 25 ± 1.6 at 3 months and 22.3 ± 2.1 at 36 months.
In 2010 Greenberg et al. published results of 26 patients who underwent bilateral DBS of the VC/VS divided over four different research centers, including 10 patients they had previously reported. Follow-up periods in these studies ranged from 3 to 36 months, averaging 31.4 months. Y-BOCS scores improved from 34.0 ± 0.5 at baseline to 20.9 ± 2.4 at the latest follow-up, with this level of improvement being apparent already 3 months after active stimulation started (Y-BOCS 21.0 ± 1.8). Furthermore, the authors note that about 65% of the patients benefitted from the treatment due to clinically significant symptom reductions and functional improvement.
Six patients who received bilateral DBS of the VC/VS were assessed in a randomized, blinded, staggered onset design. After 12 months of active stimulation 67% (i.e. four out of six) patients were classified as responders (≥35% Y-BOCS score decrease from baseline). In fact, the mean baseline Y-BOCS score of 33.7 decreased by 15.67 ± 11.60 points (mean ± SD).
In another study targeting the VC/VS bilaterally, four OCD patients were assessed every 3 months for 15 months showing a 33.6% reduction (mean ± SD, 36.3 ± 2.1 pre-operatively vs. 24.3 ± 9.1 at 15 months).
In 2013 a single case report of a 51-Year old OCD patient who received DBS of the VC/VS was published. Her Y-BOCS scores fluctuated during the course of her 22-month follow-up, remaining somewhat stagnant over the first 9 months and then decreasing more dramatically to 10 points at 12 months follow-up. However, concomitant psychotherapy makes it difficult to attribute changes to DBS alone (see Table 3).
Subthalamic Nucleus
The STN is a component of the basal ganglia and is located ventral to the thalamus, dorsal to the substantia nigra, and medial to the corticospinal tract. Experiences with DBS in patients with Parkinson's disease (PD) and comorbid OCD symptoms have suggested the involvement of the STN in OCD.
Mallet et al. described a successful stimulation of the STN in two OCD patients with improvements of 58 and 64% (pre-operative Y-BOCS 26 and 23, respectively; Y-BOCS at 6 months follow-up 5 and 4, respectively). Fontaine et al. reported a second positive case: A 49-year-old man suffering from OCD as well as PD received bilateral stimulation of the STN, reducing Y-BOCS scores from a baseline of 32 to 1 after 6 months of active stimulation.
Six years after their first report on STN DBS in OCD, Mallet et al. published a study with a double-blind crossover design by which they assess the efficacy of bilateral STN stimulation. Sixteen OCD patients were randomly assigned to active stimulation followed by sham stimulation, or vice versa, with eight patients in each group. Assessment at the end of the two 3 months periods revealed a significantly lower Y-BOCS score for patients under active stimulation (mean ± SD, 19 ± 8) compared to patients under sham stimulation (28 ± 7).
Finally, Chabardès et al. described four patients, two of them originally reported by Mallet et al.. Of the remaining two, one showed a symptom reduction of 78% (8 vs. 29) while the second patient was classified as a partial responder with an improvement of about 34% (21 vs. 32) 6 months after electrode implantation. STN-DBS data of the study by Barcia et al. revealed the following improvement in Y-BOCS scores: scores of patient 1 decreased from 33 at baseline to 20 three months follow-up and of patient 2 decreased from 33 at baseline to 18 (see Table 4).
Inferior Thalamic Peduncle
The ITP is the connecting structure between orbitofrontal cortex and thalamus and part of the orbitofrontal thalamic system. Its association with OCD symptoms makes it a promising target structure for DBS.
In 2009 Jiménez et al. reported bilateral ITP stimulation in five patients with refractory OCD. Y-BOCS scores were assessed every 3 months for a total of 12 months, showing a reduction of 51% at the last follow-up (mean ± SD, 17.8 ± 3.9 vs. 35 ± 6.2,).
Another study by Jiménez et al. assessed the efficacy of implantation of quadripolar deep brain stimulation electrodes in the ITP for six OCD patients. At 12 months follow-up a 51% decrease in Y-BOCS scores could be observed (mean ± SD, 17.5 ± 3.6 vs. 35.8 ± 5.9) which further decreased after 24 and 36 months (14.0 ± 7. 8 and 13.3 ± 5.7, respectively) (see Table 5).
Adverse Events
Complications of DBS can be classified into 3 categories. First, 'procedure related adverse events' describe complications arising from the surgery itself. Second, difficulties may originate from the implantation device ('device related'). Third, the stimulation itself may cause effects on mood or cognition that can be acute and reversible or chronic in nature and are specific to the target region. Disorder related adverse events are not discussed at this point.
Procedure Related. Overall, six patients suffered from superficial wound infections following surgery and one patient exhibited an allergic reaction to the implantation device in the chest. Dell'Osso and colleagues described a patient who, following a minor inflammation at the area where the stimulator had been implanted, developed a scar-picking behavior, making it necessary to remove the device despite major improvements in OCD symptoms.
Serious adverse events during surgery included two seizures, and three intracerebral hemorrhages.
Device Related. In five patients breaks in stimulating leads or extension wires requiring replacement were reported. One patient reported dysesthesia in the subclavicular region that lasted for several weeks. Okun and colleagues reviewed symptoms potentially related to battery failure in 6 patients with refractory OCD, noting that suicidality, mood disturbance, panic attacks, fatigue, and a restless sensation in the extremities may be associated with battery failure. Nuttin et al., as well as Denys and colleagues reported on several patients who felt the leads or stimulation devices (5 permanent and 7 transient cases).
Stimulation Related. Anxiety: Twenty-five patients in four studies (three NAc studies, one VC/VS study) experienced an acute increase in anxiety. All of these were induced either by a change of stimulation parameters, or by battery depletion, so that anxiety symptoms were quickly resolved after parameter adaption or pacemaker exchange.
Mood: The most common effect on mood during chronic DBS was hypomania, experienced by 27 patients across five studies (two NAc studies and three VC/VS studies) -. In all cases mood elevation responded to parameter adjustment. One patient exhibited hypomania-like symptoms during initial DBS programming. Furthermore, Greenberg et al. reported irritability leading to domestic problems in one patient. Increased depression and suicidal thoughts were noted in six patients across three studies (one ALIC study, one NAc study, and one VC/VS study). It should be noted, however, that some of these patients reported similar episodes prior to surgery. One patient in the study by Abelson et al. whose symptoms were reduced after DBS, committed suicide one year after surgery and stated in a note that her suicide was unrelated to the study.
Cognition: Effects of DBS on cognition in patients suffering from OCD seem to occur only rarely. Some patients reported cognitive 'clouding' or diminished concentration in two studies. However, these were related only to certain parameter settings, and thus readily reversible. In the same study activation of the most dorsal contact during operation resulted in verbal perseveration in one patient. Three subjects in a study by Denys et al. reported words-finding difficulties. In eight patients across two studies DBS affected memory performance: one patient had brief flashbacks that recurred several times a day, which could be resolved with changing stimulation parameters, the memory problems in the other seven patients were transient and resolved over time.
Other. Next to these psychological effects some authors noted various other effects that may be attributed to DBS. These range from difficulties falling asleep over vertigo and weight loss or gain to long-lasting fatigue. Also an increased headache frequency and a single case of a visual disturbance in the left eye have been noted.
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