Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation.

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson's disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Focused ultrasound in neurosurgery: a historical perspective.

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

Toward adaptive deep brain stimulation for dystonia.

The presence of abnormal neural oscillations within the cortico-basal ganglia-thalamo-cortical (CBGTC) network has emerged as one of the current principal theories to explain the pathophysiology of movement disorders. In theory, these oscillations can be used as biomarkers and thereby serve as a feedback signal to control the delivery of deep brain stimulation (DBS). This new form of DBS, dependent on different characteristics of pathological oscillations, is called adaptive DBS (aDBS), and it has already been applied in patients with Parkinson's disease. In this review, the authors summarize the scientific research to date on pathological oscillations in dystonia and address potential biomarkers that might be used as a feedback signal for controlling aDBS in patients with dystonia.

Deep brain stimulation for the treatment of drug addiction.

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.

A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies.

OBJECTIVE Minimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator. METHODS Using an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson's disease to investigate the feasibility of its application in brain. RESULTS Thermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson's disease. CONCLUSIONS The authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

Approaches to closed-loop deep brain stimulation for movement disorders.

OBJECTIVE Deep brain stimulation (DBS) is a safe and effective therapy for movement disorders, such as Parkinson's disease (PD), essential tremor (ET), and dystonia. There is considerable interest in developing "closed-loop" DBS devices capable of modulating stimulation in response to sensor feedback. In this paper, the authors review related literature and present selected approaches to signal sources and approaches to feedback being considered for deployment in closed-loop systems. METHODS A literature search using the keywords "closed-loop DBS" and "adaptive DBS" was performed in the PubMed database. The search was conducted for all articles published up until March 2018. An in-depth review was not performed for publications not written in the English language, nonhuman studies, or topics other than Parkinson's disease or essential tremor, specifically epilepsy and psychiatric conditions. RESULTS The search returned 256 articles. A total of 71 articles were primary studies in humans, of which 50 focused on treatment of movement disorders. These articles were reviewed with the aim of providing an overview of the features of closed-loop systems, with particular attention paid to signal sources and biomarkers, general approaches to feedback control, and clinical data when available. CONCLUSIONS Closed-loop DBS seeks to employ biomarkers, derived from sensors such as electromyography, electrocorticography, and local field potentials, to provide real-time, patient-responsive therapy for movement disorders. Most studies appear to focus on the treatment of Parkinson's disease. Several approaches hold promise, but additional studies are required to determine which approaches are feasible, efficacious, and efficient.

Deep brain stimulation for dementias.

OBJECTIVE The aim of this article is to review the authors' and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events. RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations. CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

High-intensity focused ultrasound: past, present, and future in neurosurgery.

Since Lynn and colleagues first described the use of focused ultrasound (FUS) waves for intracranial ablation in 1942, many strides have been made toward the treatment of several brain pathologies using this novel technology. In the modern era of minimal invasiveness, high-intensity focused ultrasound (HIFU) promises therapeutic utility for multiple neurosurgical applications, including treatment of tumors, stroke, epilepsy, and functional disorders. Although the use of HIFU as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists, neurologists, or even neurosurgeons are familiar with it. In this extensive review, the authors intend to shed light on the current use of HIFU in different neurosurgical avenues and its mechanism of action, as well as provide an update on the outcome of various trials and advances expected from various preclinical studies in the near future. Although the initial technical challenges have been overcome and the technology has been improved, only very few clinical trials have thus far been carried out. The number of clinical trials related to neurological disorders is expected to increase in the coming years, as this novel therapeutic device appears to have a substantial expansive potential. There is great opportunity to expand the use of HIFU across various medical and surgical disciplines for the treatment of different pathologies. As this technology gains recognition, it will open the door for further research opportunities and innovation.

Preliminary experience with a transcranial magnetic resonance-guided focused ultrasound surgery system integrated with a 1.5-T MRI unit in a series of patients with essential tremor and Parkinson's disease.

OBJECTIVE Transcranial magnetic resonance-guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson's disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world's first tcMRgFUS system integrated with a 1.5-T MRI unit. METHODS The authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was performed in both ET and PD patients. In all the tcMRgFUS treatments, a 1.5-T MRI scanner was used for both planning and monitoring the procedure. RESULTS During the study period, a total of 26 patients underwent tcMRgFUS thalamic ablation for different movement disorders. Among these patients, 18 were diagnosed with ET and 4 were affected by PD. All patients with PD were treated using tcMRgFUS thalamic ablation and all completed the procedure. Among the 18 patients with ET, 13 successfully underwent tcMRgFUS, 4 aborted the procedure during ultrasound delivery, and 1 did not undergo the tcMRgFUS procedure after stereotactic frame placement. Two patients with ET were not included in the results because of the short follow-up duration at the time of this study. A monolateral VIM thalamic ablation in both ET and PD patients was performed. All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. A global reevaluation was performed 3 months (17/22 patients) and 6 months (11/22 patients) after the treatment; the reevaluation consisted of clinical questionnaires, neurological tests, and video recordings of the tests. All the ET and PD treated patients who completed the procedure showed an immediate amelioration of tremor severity, with no intra- or posttreatment severe permanent side effects. CONCLUSIONS Although this study reports on a small number of patients with a short follow-up duration, the tcMRgFUS procedure using a 1.5-T MRI unit resulted in a safe and effective treatment option for motor symptoms in patients with ET and PD. To the best of the authors' knowledge, this is the first clinical series in which thalamotomy was performed using tcMRgFUS integrated with a 1.5-T magnet.

Neuromodulation for restoring memory.

Disorders of learning and memory have a large social and economic impact in today's society. Unfortunately, existing medical treatments have shown limited clinical efficacy or potential for modification of the disease course. Deep brain stimulation is a successful treatment for movement disorders and has shown promise in a variety of other diseases including psychiatric disorders. The authors review the potential of neuromodulation for the treatment of disorders of learning and memory. They briefly discuss learning circuitry and its involvement in Alzheimer disease and traumatic brain injury. They then review the literature supporting various targets for neuromodulation to improve memory in animals and humans. Multiple targets including entorhinal cortex, fornix, nucleus basalis of Meynert, basal ganglia, and pedunculopontine nucleus have shown a promising potential for improving dysfunctional memory by mechanisms such as altering firing patterns in neuronal networks underlying memory and increasing synaptic plasticity and neurogenesis. Significant work remains to be done to translate these findings into durable clinical therapies.

The role of diffusion tensor imaging and fractional anisotropy in the evaluation of patients with idiopathic normal pressure hydrocephalus: a literature review.

OBJECTIVE Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention. METHODS The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: "Alzheimer's disease," "brain," "cerebrospinal fluid," "CSF," "diffusion tensor imaging," "DTI," "hydrocephalus," "idiopathic," "magnetic resonance imaging," "normal pressure," "Parkinson's disease," and "shunting." Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles. RESULTS The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers. CONCLUSIONS Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.

Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology.

Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors' knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach.

Postoperative symptoms of psychosis after deep brain stimulation in patients with Parkinson's disease.

OBJECT: Cases of postoperative psychosis in Parkinson's disease patients receiving deep brain stimulation (DBS) treatment have previously been published. However, the magnitude of symptom incidence and the clinical risk factors are currently unknown. This retrospective study sheds light on these issues by investigating psychosis in a group of 128 Parkinson's disease patients who received DBS implants. METHODS: A retrospective chart review was performed to obtain surgery dates, follow-up clinic visit dates, and associated stimulation parameter settings (contacts in use and the polarity of each along with stimulation voltage, frequency, and pulse width) for each patient. Unified Parkinson's Disease Rating Scale II Thought Disorder scores, used as a clinical assessment tool to evaluate the presence of psychosis at each visit, were also collected. The data were compiled into a database and analyzed. RESULTS: The lifetime incidence of psychosis in this cohort of patients was 28.1%. The data suggest that risk of psychosis remains fairly constant throughout the first 5 years after implantation of a DBS system and that patients older at the time of receiving the first DBS implant are not only more likely to develop psychosis, but also to develop symptoms sooner than their younger counterparts. Further analysis provides evidence that psychosis is largely independent of the clinically used electrode contact and of stimulation parameters prior to psychosis onset. CONCLUSIONS: Although symptoms of psychosis are widely seen in patients with Parkinson's disease in the years following stimulator placement, results of the present suggest that most psychoses occurring postoperatively are likely independent of implantation and stimulation settings.

Role of apolipoprotein E polymorphism as a prognostic marker in traumatic brain injury and neurodegenerative disease: a critical review.

OBJECT The difference in course and outcome of several neurodegenerative conditions and traumatic injuries of the nervous system points toward a possible role of genetic and environmental factors as prognostic markers. Apolipoprotein E (Apo-E), a key player in lipid metabolism, is recognized as one of the most powerful genetic risk factors for dementia and other neurodegenerative diseases. In this article, the current understanding of APOE polymorphism in various neurological disorders is discussed. METHODS The English literature was searched for various studies describing the role of APOE polymorphism as a prognostic marker in neurodegenerative diseases and traumatic brain injury. The wide ethnic distribution of APOE polymorphism was discussed, and the recent meta-analyses of role of APOE polymorphism in multiple diseases were analyzed and summarized in tabular form. RESULTS Results from the review of literature revealed that the distribution of APOE is varied in different ethnic populations. APOE polymorphism plays a significant role in pathogenesis of neurodegeneration, particularly in Alzheimer's disease. APOE ε4 is considered a marker for poor prognosis in various diseases, but APOE ε2 rather than APOE ε4 has been associated with cerebral amyloid angiopathy-related bleeding and sporadic Parkinson's disease. The role of APOE polymorphism in various neurological diseases has not been conclusively elucidated. CONCLUSIONS Apo-E is a biomarker for various neurological and systemic diseases. Therefore, while analyzing the role of APOE polymorphism in neurological diseases, the interpretation should be done after adjusting all the confounding factors. A continuous quest to look for associations with various neurological diseases and wide knowledge of available literature are required to improve the understanding of the role of APOE polymorphism in these conditions and identify potential therapeutic targets.

Deep brain stimulation for obesity: rationale and approach to trial design.

Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

Predictors of unfavorable outcomes following deep brain stimulation for movement disorders and the effect of hospital case volume on outcomes: an analysis of 33, 642 patients across 234 US hospitals using the National (Nationwide) Inpatient Sample from 2002 to 2011.

OBJECT: With limited data available on association of risk factors and effect of hospital case volume on outcomes following deep brain stimulation (DBS), the authors attempted to identify these associations using a large population-based database. METHODS: The authors performed a retrospective cohort study involving patients who underwent DBS for 3 primary movement disorders: Parkinson's disease, essential tremor, and dystonia from 2002 to 2011 using the National (Nationwide) Inpatient Sample (NIS) database. Using national estimates, the authors identified associations of patient demographics, clinical characteristics, and hospital characteristics on short-term postoperative outcomes following DBS. Additionally, effect of hospital volume on unfavorable outcomes was investigated. RESULTS: Overall, 33, 642 patients underwent DBS for 3 primary movement disorders across 234 hospitals in the US. The mean age of the cohort was 63.42 ± 11.31 years and 36% of patients were female. The inpatients' postoperative risks were 5.9% for unfavorable discharge, 10.2% for prolonged length of stay, 14.6% for high-end hospital charges, 0.5% for wound complications, 0.4% for cardiac complications, 1.8% for venous thromboembolism, and 5.5% for neurological complications, including those arising from an implanted nervous system device. Compared with low-volume centers, odds of having an unfavorable discharge, prolonged LOS, high-end hospital charges, wound, and cardiac complications were significantly lower in the high-volume and medium-volume centers. CONCLUSIONS: The authors' study provides individualized estimates of the risks of postoperative complications based on patient demographics and comorbidities and hospital characteristics, which could potentially be used as an adjunct for risk stratification for patients undergoing DBS.

Deep brain stimulation for psychiatric disorders: where we are now.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Delayed hemorrhage following deep brain stimulation device placement in a patient with Parkinson's disease and lupus anticoagulant syndrome: illustrative case.

BACKGROUND: Treatment options for Parkinson's disease (PD) include both medical and surgical approaches. Deep brain stimulation (DBS) is a surgical procedure that aims to improve motor symptomatology. OBSERVATIONS: A 66-year-old White male with a 9-year history of PD presented to the neurosurgery clinic for DBS consideration. On the morning of scheduled surgery, preoperative laboratory test results revealed a prolonged prothrombin time of 50 seconds. Surgery was postponed, and further work-up revealed that the patient had a positive test result for lupus anticoagulant (LA). DBS implantation was performed 2 months later. The first stage of surgery was uneventful. The patient returned 1 week later for the second stage. Postoperatively, the patient exhibited a diminished level of consciousness. Computed tomography revealed left frontal intraparenchymal hemorrhage with surrounding edema, trace subarachnoid hemorrhage, intraventricular hemorrhage, and midline shift. LESSONS: The authors suspect that the hemorrhage occurred secondary to venous infarct, because LA is associated with a paradoxically increased risk of thrombosis. Although there is no documented association between LA and acute or delayed hemorrhage, this case demonstrates a possible relationship in a patient following DBS placement. More research is needed to confirm an association with coexisting LA with PD and an increased hemorrhage risk in neurosurgical interventions.

Secondary parkinsonism caused by chronic subdural hematomas owing to compressed cortex and a disturbed cortico-basal ganglia-thalamocortical circuit: illustrative case.

BACKGROUND: Chronic subdural hematoma (CSDH) is a commonly encountered condition in neurological and neurosurgical practice, but the presence of concomitant parkinsonism is extremely rare. Basal ganglia disturbance is a well-known underlying mechanism; however, few cases present with cerebral cortex compression as the cause of symptoms. OBSERVATIONS: A 52-year-old man was referred to the authors' hospital with a 5-week history of gait disturbance and suspected Parkinson's disease. Neurological examination revealed a mask-like face, stooped posture, left-predominant rigidity, and postural instability. The authors initiated dopamine agonist administration, and brain magnetic resonance imaging (MRI) was scheduled. One week later, MRI showed bilateral CSDHs. The hematomas markedly compressed the bilateral cerebral cortex, whereas the midbrain and basal ganglia structures were intact. The patient underwent burr hole drainage and was discharged after 9 days without sequelae. LESSONS: CSDH can cause parkinsonism by compressing the cerebral cortex, which is a part of the cortico-basal ganglia-thalamocortical circuit. Surgery leads to positive outcomes, as illustrated by this case, in which cerebral cortex compression caused parkinsonism.

Selection of deep brain stimulation contacts using volume of tissue activated software following subthalamic nucleus stimulation.

OBJECTIVE: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in the treatment of motor symptoms of Parkinson's disease. Using a patient-specific lead and volume of tissue activated (VTA) software, it is possible to visualize contact positions in the context of the patient's own anatomy. In this study, the authors' aim was to demonstrate that VTA software can be used in clinical practice to help determine the clinical effectiveness of stimulation in patients with Parkinson's disease undergoing DBS of the STN. METHODS: Brain images of 26 patients undergoing STN DBS were analyzed using VTA software. Preoperative clinical and neuropsychological data were collected. Contacts were chosen by two experts in DBS blinded to the clinical data. A therapeutic window of amplitude was determined. These results were compared with the parameter settings for each patient. Data were obtained at 3 months and 1 year postsurgery. RESULTS: In 90.4% (95% CI 82%-98%) of the patients, the contacts identified by the VTA software were concordant with the clinically effective contacts or with an effective contact in contact-by-contact testing. The therapeutic window of amplitude selected virtually included 81.3% of the clinical amplitudes. CONCLUSIONS: VTA software appears to present significant concordance with clinical data for selecting contacts and stimulation parameters that could help in postoperative follow-up and programming.