Wolfgang Huff

Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year.

OBJECTIVE To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized. METHODS The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function. RESULTS The mean Y-BOCS scores decreased significantly from 32.2 (+/-4.0) at baseline to 25.4 (+/-6.7) after 12 months (p=0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated. CONCLUSIONS DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.

Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome

Sirs: Tourette Syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood, characterized by the chronic occurrence of motor and vocal tics. High rates of comorbidity with other psychiatric disorders, such as obsessive compulsive disorders (OCD) are to be found. OCD symptoms, which almost always accompany TS, are even discussed as constituting an integral component of the phenomenology of the disorder. Pharmacological treatment of the tics of TS centres predominantly on the use of neuroleptics. Patients with comorbid OCD can additionally benefit from clomipramine and selective serotonin reuptake inhibitors. Despite maximum dosage and combination of all known therapeutic approaches, a number of seriously affected individuals fail to experience satisfactory treatment results. In light of initially successful experimental treatment of TS using deep brain stimulation (DBS) it is hoped that this approach may, in the future, provide an alternative therapeutic option for pharmacologically refractory individuals. We report on a 26 year old male patient suffering, from puberty onwards, from a serious TS. The disorder is characterized by a broad spectrum of high-frequency simple and complex motor and vocal tics. Massive impairment is especially induced by autoaggressive and automutilative tics, as well as repetitive spitting and coprolalia. The disorder is additionally complicated by a severe OCD. The case history of the patient documents the unsuccessful administration of maximum doses and combinations of established treatments. The gravity of the disorder is substantiated by the fact that the patient has found himself in continuous in-patient psychiatric treatment since puberty. Furthermore, the patient has for the most part of this treatment period been physically restrained in order to prevent self injury. On account of this history, we considered a therapeutic trial using DBS to be indicated. Based on our experiences and the beneficial results gained in a pilot series of patients with intractable OCD and anxiety disorders [15], we selected the region of the nucleus accumbens (NA) as primary target for DBS in our patient with TS and comorbid OCD. Access and electrode trajectories were determined by a computer-supported image fusion of MRI and intraoperative CT. 3-D coordinates for localisation of the target point were as follows: 2,5 mm rostral anterior border of AC, 6,5 mm lateral of midline, 4,5 mm ventral AC. Stereotactically guided implantation of quadripolar electrodes (Medtronic 3387; Medtronic, Inc., Minneapolis, MN) was carried out under general anaesthetic. The correct positioning of these was postoperatively confirmed by means of CT and conventional x-ray procedures (pole 0,1: fundus subventricularis medialis of the nucleus accumbens; pole 2,3: anterior limb of the internal capsule). A pulse generator (Kinetra, Medtronic, Inc., Minneapolis, MN) connected to the electrodes was implanted inferior to the clavicles. During a post-operative phase of adjustment lasting a few months, the following settings appeared most effective: ()0,)1,)2,)3 anode; + case cathode; pulse width 90 ls, 130 Hz, 7 V); although these parameter settings also resulted in an extremely high energy consumption. Under application of DBS with the aforementioned parameters, the patient showed a significant reduction in both the frequency and gravity of his tics over the course of a two and half year observation period. Remission rates of 41% and 50% were found based on measurements with the Yale Global Tic Severity Scale [12] and the Modified Rush Video Rating Scale [7] respectively (Figure 1). Tics involving self injury were especially reduced and symptoms of coprolalia disapJ. Kuhn, MD (&) Æ W. Huff, MD S.-H. Lee, MD Æ J. Klosterkoetter, MD Dept. of Psychiatry and Psychotherapy University of Cologne Kerpener Strasse 62 50924 Cologne, Germany Tel.: +49-221/478-4005 E-Mail: Jens.Kuhn@uk-koeln.de

Observations on Unaided Smoking Cessation after Deep Brain Stimulation of the Nucleus Accumbens

Aims: We explore whether clinical research on deep brain stimulation (DBS) of the nucleus accumbens (NAc) to treat addiction is justified besides theoretical speculation. Methods: Since 2004, 10 patients who were also smokers were treated at the University of Cologne for Tourette’s syndrome (TS), obsessive-compulsive disorders (OCD) or anxiety disorders (AD) by DBS of the NAc. We assessed their smoking behavior after DBS and (in retrospection) before by the Fagerström Test for Nicotine Dependence (FTND) and additional items. Results: Three male patients were able to quit smoking after DBS. They were less dependent and higher motivated compared to the rest of the sample. They are stimulated with a higher voltage. During 1-year, 2-year, and 30-month follow-ups, we found a higher rate of successful smoking cessation (20, 30 and 30%) compared to unaided smoking cessation in the general population (13, 19 and 8.7%). Conclusions: Albeit the results of the study are severely limited by the method of retrospective self-assessment of psychiatric patients, further research of DBS of the NAc to treat addiction seems justified. In addition to biological mediators, psychosocial factors should be assessed in further prospective studies.

Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders

BACKGROUND To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group. METHOD PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score >61 (Global Assessment of Functioning Scale), SOFAS score >61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore >40 (Medical Outcomes Study-Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid clinical and sociodemographic predictors. RESULTS In total, 52 patients (20%) fulfilled the criteria for functional remission, 125 patients (48%) achieved symptomatic resolution and when criteria for functional remission and symptomatic resolution were combined 33 patients (13%) achieved complete remission. Younger age, employment, a shorter duration of illness, a shorter length of current episode, less suicidality, and a lower PANSS negative and global subscore at admission were predictive of functional remission. The regression model showed a predictive value of more than 80%. CONCLUSIONS A significant association was found between functional remission and symptomatic resolution, indicating reasonable validity of the proposed definition for functional outcome. The revealed predictors for functional treatment outcome emphasize the need for psychosocial and vocational rehabilitation in schizophrenic patients.

Disappearance of self-aggressive behavior in a brain-injured patient after deep brain stimulation of the hypothalamus: technical case report.

OBJECTIVE Self-mutilation is a severe symptom of diseases with varying etiologies. It can be observed in the context of mental retardation and after traumatic brain injury. Pharmacological treatment approaches often prove ineffective. CLINICAL PRESENTATION We report the case of a 22-year-old woman with repetitive self-mutilating behavior in the mouth area after severe traumatic brain injury. RESULTS Bilateral deep brain stimulation of the posterior hypothalamus was conducted and resulted in the complete elimination of self-mutilation during a 4-month observation period. CONCLUSION This technical case report indicates that deep brain stimulation of the posterior hypothalamus could be a promising approach in the treatment of severe self-mutilating behavior.

Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. METHOD A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). RESULTS Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. CONCLUSIONS Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159120.

Transient Manic-like Episode Following Bilateral Deep Brain Stimulation of the Nucleus Accumbens and the Internal Capsule in a Patient With Tourette Syndrome.

Objective.  Deep brain stimulation (DBS) increasingly attracts attention as a potential treatment of mental disorders. Beside depression and obsessive–compulsive disorders, DBS has already been shown to be beneficial for Tourette syndrome (TS).

Depression during an acute episode of schizophrenia or schizophreniform disorder and its impact on treatment response

The aim of the present study was to examine the relevance of depressive symptoms during an acute schizophrenic episode for the prediction of treatment response. Two hundred inpatients who fulfilled DSM-IV criteria for schizophrenia or schizophreniform disorders were assessed at hospital admission and after 6 weeks of inpatient treatment using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale for Depression (HAM-D). Depressive symptoms showed positive correlations with both positive and negative symptoms at admission and after 6 weeks, and decreased during 6 weeks of treatment. Pronounced depressive symptoms (HAM-D score> or =16) were found in 28% of the sample at admission and in 9% after 6 weeks of treatment. Depressive symptoms at admission predicted a greater improvement of positive and negative symptoms over 6 weeks of treatment, but also more, rather than fewer remaining symptoms after 6 weeks. Both results, however, lost statistical significance when analyses were controlled for the influence of positive and negative symptoms at admission. Therefore, the hypothesis that depressive symptoms are predictive of a favorable treatment response was not supported by the present study.

Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications?

Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient’s comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.

40. Deep brain stimulation in the nucleus accumbens – outcomes after one year stimulation in patients with treatment resistant obsessive compulsive disorder

In this functional magnetic resonance imaging study, we examined changes in cortical activation and connectivity in two patients following unilateral heterotopic replantation of the hand and distal forearm to the upper arm for proximal forearm tumours. The patients and a group of healthy controls performed visually paced hand movements with their left, right, or both hands. Effective connectivity during this task was assessed among a bilateral motor network – comprising primary motor cortex (M1), lateral premotor cortex (PMC), and supplementary motor area (SMA) – using dynamic causal modelling. When moving the normal hand both patients showed inhibition of the ipsilateral PMC and SMA, indicating a suppression of inference by the hemisphere controlling the replanted hand on physiological motor execution. Moving the replantated hand both patients showed increased activation of the PMC contralateral to surgery (reflecting increased effort), and a pathological inhibition exerted by the ipsilateral M1 on its active contralateral homologue indicative of a disturbed modulation of the inhibitory M1–M1 balance. In one patient, M1 contralateral to surgery received increased tonic (intrinsic connectivity) and phasic (replantated hand movement) facilitating input, whereas in the other patient pathological suppression was present. These differences in connectivity correlated with a reduced behavioural performance of the latter patient as assessed by kinematic analysis. Moreover, the increased recruitment of the contralateral M1 and the concurrent superior behavioural outcome seem to be related to an earlier and more intense rehabilitation commenced in the first patient. This study demonstrates the potential of functional neuroimaging to monitor plastic changes of cortical connectivity between cortical motor areas due to peripheral nerve surgery and subsequent recovery in individual patients, which may provide a valuable tool to understand, evaluate and enhance motor rehabilitation.