Pantelis Stathis

Technical aspects and considerations of deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) represents one of the more recent advancements in Neurosurgery. Even though its most successful applications evolved in movement disorders (MDs), indications now include pain, psychiatric disorders, epilepsy, cluster headaches and Tourette syndrome. As this type of surgery gains popularity and the indications for DBS surgery increase, so it will certainly increase the number of neurosurgeons who will use this neuromodulatory technique. A detailed description of the technical aspects of the DBS procedure, as it is performed in our department, is presented. In our opinion, our method is a good combination of all the well-established necessary techniques in a cost-effective way. This technical article may be helpful to neurosurgeons considering to start performing this type of surgery. It could also prompt others who perform DBS regularly to express their views, and hence, lead to further refinement of this demanding procedure.

Connections of the basal ganglia with the limbic system: implications for neuromodulation therapies of anxiety and affective disorders

The basal ganglia are best known for their role in motor planning and execution. However, it is currently widely accepted that they are also involved in cognitive and emotional behaviors. Parts of the basal ganglia play a key role in reward and reinforcement, addictive behaviors and habit formation. Pathophysiological processes underlying psychiatric disorders such as depression, obsessive compulsive disorder and even schizophrenia involve the basal ganglia and their connections to many other structures and particularly to the prefrontal cortex and the limbic system. In this article, we aim, on the basis of current research, to describe in a succinct manner the most important connections of the basal ganglia with the limbic system which are relevant to normal behaviors but also to psychiatric disorders. Currently, we possess sufficiently powerful tools that enable us to modulate brain networks such as cortex stimulation (CS) or deep brain stimulation (DBS). Notably, neuromodulation of basal ganglia function for the treatment of movement disorders has become a standard practice, which provides insights into the psychiatric problems that occur in patients with movement disorders. It is clear that a sound understanding of the currently available knowledge on the circuits connecting the basal ganglia with the limbic system will provide the theoretical platform that will allow precise, selective and beneficial neuromodulatory interventions for refractory psychiatric disorders.

Risperidone: a novel antipsychotic with many “atypical” properties?

The acute and chronic administration effects of risperidone (Ris), a mixed 5HT2/D2 receptor antagonist, versus haloperidol (Hal) on dopaminergic and serotoninergic activity were investigated in the rat prefrontal cortex (Pfc), and the whole striatum (Str) as well as separately, in dorsal striatum (StrD) and nucleus accumbens (Acb). During acute administration, Hal was found to be more potent than Ris in increasing DA turnover rate in StrD. In contrast, during chronic administration, Ris but not Hal, continued to increase DA turnover activity in StrD. Moreover, in contrast to Hal, chronic Ris treatment continued to increase DA and 5-HT turnover rate in Pfc. These differential effects reveal that Hal does not share common characteristics with Ris with respect to its neurochemical profile in the Str and Pfc.

An Observational Trial to Investigate the Efficacy and Tolerability of Levetiracetam in Trigeminal Neuralgia

Objective.— To explore the efficacy and tolerability of levetiracetam in medical treatment of trigeminal neuralgia.

The effects of antipsychotic drugs on serotonergic activity in the rat hippocampus

The serotonergic activity in hippocampus was investigated following acute and chronic treatment with the antipsychotic drugs haloperidol and risperidone. Acute administration of risperidone, the serotonin(2) (5-HT(2)) receptor antagonist ketanserin, and the dopamine (DA)-D(2) receptor antagonist raclopride increased the 5-hydroxyindoleacetic acid/serotonin (5-HIAA/5-HT) ratio. In contrast, acute administration of haloperidol did not affect this ratio. Chronic administration of risperidone maintained the increased 5-HIAA/5-HT ratio; a challenge dose of risperidone after the chronic treatment and the subsequent washout period also maintained the increased ratio. Chronic administration of haloperidol as well as a challenge dose of haloperidol following chronic treatment did not affect the serotonergic activity in hippocampus. Administration of ketanserin or raclopride after chronic treatment and the washout period induced an additional increase in the 5-HIAA/5-HT ratio in risperidone-treated rats. Moreover, a challenge dose of ketanserin, but not raclopride, increased the 5-HIAA/5-HT ratio in haloperidol-treated rats. The present results indicate that acute and chronic treatment of haloperidol or risperidone modified serotonergic activity in the hippocampus in a different way. Moreover, the augmentation of serotonergic activity induced by risperidone did not seem to be solely related to dopaminergic or serotonergic properties and may be of particular relevance for the amelioration of schizophrenia symptoms.

Beta-Band Frequency Peaks Inside the Subthalamic Nucleus as a Biomarker for Motor Improvement After Deep Brain Stimulation in Parkinson's Disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains an empirical, yet highly effective, surgical treatment for advanced Parkinsons disease (PD). DBS outcome depends on accurate stimulation of the STN sensorimotor area which is a trial-and-error procedure taking place during and after surgery. Pathologically enhanced beta-band (13-35 Hz) oscillatory activity across the cortico-basal ganglia pathways is a prominent neurophysiological phenomenon associated with PD. We hypothesized that weighing together beta-band frequency peaks from simultaneous microelectrode recordings in “off-state” PD patients could map the individual neuroanatomical variability and serve as a biomarker for the location of the STN sensorimotor neurons. We validated our hypothesis with 9 and 11 patients that, respectively, responded well and poorly to bilateral DBS, after at least two years of follow up. We categorized “good” and “poor” DBS responders based on their clinical assessment alongside a > 40% and <;30% change, respectively, in “off” unified PD rating scale motor scores. Good (poor) DBS responders had, in average, 1 mm (3.5 mm) vertical distance between the maximum beta-peak weighted across the parallel microelectrodes and the center of the stimulation area. The distances were statistically different in the two groups (p = 0.0025). Our biomarker could provide personalized intra- and postoperative support in stimulating the STN sensorimotor area associated with optimal long-term clinical benefits.

Treatment of idiopathic head drop (camptocephalia) by deep brain stimulation of the globus pallidus internus

Deep brain stimulation of the globus pallidus internus has been shown to be beneficial in a small number of patients suffering from axial dystonias. However, it has not yet been reported as an effective treatment for the alleviation of idiopathic head drop. The authors describe a 49-year-old woman with idiopathic cervical dystonia (camptocephalia) who was unable to raise her head > 30 degrees when standing or sitting; her symptoms would abate when lying down. This disabling neurological condition was treated successfully with bilateral chronic electrical stimulation of the globus pallidus internus.

Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

BackgroundThe neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinsons disease.Case presentationWe present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man.ConclusionThe characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinsons disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patients recovery.

Dominant efficiency of nonregular patterns of subthalamic nucleus deep brain stimulation for Parkinson's disease and obsessive-compulsive disorder in a data-driven computational model.

OBJECTIVE Almost 30 years after the start of the modern era of deep brain stimulation (DBS), the subthalamic nucleus (STN) still constitutes a standard stimulation target for advanced Parkinsons disease (PD), but the use of STN-DBS is also now supported by level I clinical evidence for treatment-refractory obsessive-compulsive disorder (OCD). Disruption of neural synchronization in the STN has been suggested as one of the possible mechanisms of action of standard and alternative patterns of STN-DBS at a local level. Meanwhile, recent experimental and computational modeling evidence has signified the efficiency of alternative patterns of stimulation; however, no indications exist for treatment-refractory OCD. Here, we comparatively simulate the desynchronizing effect of standard (regular at 130 Hz) versus temporally alternative (in terms of frequency, temporal variability and the existence of bursts or pauses) patterns of STN-DBS for PD and OCD, by means of a stochastic dynamical model and two microelectrode recording (MER) datasets. APPROACH The stochastic model is fitted to subthalamic MERs acquired during eight surgical interventions for PD and eight surgical interventions for OCD. For each dynamical system simulated, we comparatively assess the invariant density (steady-state phase distribution) as a measure inversely related to the desynchronizing effect yielded by the applied patterns of stimulation. MAIN RESULTS We demonstrate that high (130 Hz)-and low (80 Hz)-frequency irregular patterns of stimulation, and low-frequency periodic stimulation interrupted by bursts of pulses, yield in both pathologic conditions a significantly stronger desynchronizing effect compared with standard STN-DBS, and distinct alternative patterns of stimulation. In PD, values of the invariant density measure are proven to be optimal at the dorsolateral oscillatory region of the STN including sites with the optimal therapeutic window. SIGNIFICANCE In addition to providing novel insights into the efficiency of low-frequency nonregular patterns of STN-DBS for advanced PD and treatment-refractory OCD, this work points to a possible correlation of a model-based outcome measure with clinical effectiveness of stimulation and may have significant implications for an energy- and therapeutically-efficient configuration of a closed-loop neuromodulation system.

Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model.

OBJECTIVE During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinsons disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. APPROACH The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. MAIN RESULTS Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. SIGNIFICANCE The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise target finalization during DBS surgery for PD.