A Three-dimensional Deformable Brain Atlas for DBS Targeting. I. Methodology for Atlas Creation and Artifact Reduction.

BackgroundTargeting in deep brain stimulation (DBS) relies heavily on the ability to accurately localize particular anatomic brain structures. Direct targeting of subcortical structures has been limited by the ability to visualize relevant DBS targets.Methods and resultsIn this work, we describe the development and implementation, of a methodology utilized to create a three dimensional deformable atlas for DBS surgery. This atlas was designed to correspond to the print version of the Schaltenbrand-Bailey atlas structural contours. We employed a smoothing technique to reduce artifacts inherent in the print version.ConclusionsWe present the methodology used to create a three dimensional patient specific DBS atlas which may in the future be tested for clinical utility

Deep Brain Stimulation Management of Essential Tremor with Dystonic Features

Clinical Vignette: A 64-year-old female with essential tremor (ET) presents for evaluation of deep brain stimulation (DBS) candidacy. Examination revealed subtle dystonic features as well as a disabling postural-action tremor. Clinical Dilemma: Can dystonia occur in the setting of the diagnosis of ET and can its presence alter DBS target selection? Clinical Solution: Unilateral DBS implantation of the ventralis intermedius (Vim) led to improvement in both tremor and dystonic posturing. Gap in Knowledge: Case reports of DBS in dystonic tremor suggest Vim, globus pallidus internus (GPi), and subthalamic targets may all be effective, to varying degrees, in improving both tremor and dystonia. More rigorous studies are needed to identify the optimal target(s). Expert Commentary: This case underscores the limited evidence available to guide a clinician’s choice of DBS targets in patients with ET and dystonia. The severity of the dystonia and the presence of more generalized dystonia may alter the thinking about optimal targeting. Vim, GPi, and subthalamic targets appear potentially acceptable options, though Vim is usually the first target attempted when postural-action tremor is the chief complaint. Occasionally, a second rescue DBS lead may be necessary

Shell Shock: Psychogenic Gait and Other Movement Disorders—A Film Review

Background: The psychological pressure on soldiers during World War I (WWI) and other military conflicts has resulted in many reported cases of psychogenic gait as well as other movement disorders. In this paper, psychogenic movement disorders captured in the WWI film footage “War Neuroses” is reanalyzed. Methods: Two movement disorders specialists re-examined film images of 21 WWI patients with various and presumed psychogenic manifestations, pre- and post treatment. The film was recorded by Arthur Hurst, a general physician with an interest in neurology. Results: All 21 subjects were males, and all presented with symptoms relating to war trauma or a psychological stressor (e.g., being buried, shrapnel wounds, concussion, or trench fever). The most common presenting feature was a gait disorder, either pure or mixed with another movement disorder (15), followed by retrograde amnesia (2), abnormal postures (pure dystonia) (1), facial spasm (1), head tremor (1), “hyperthyroidism-hyperadrenalism” (1). Nineteen patients received treatment, and the treatment was identified in nine cases. In most cases, treatment was short and patients improved almost immediately. Occupational therapy was the most common treatment. Other effective methods were hypnosis (1), relaxation (1), passive movements (2), and probable “persuasion and re-education” (6). Discussion: The high success rate in treating psychogenic disorders in Hurst's film would be considered impressive by modern standards, and has raised doubt in recent years as to whether parts of the film were staged and/or acted

Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders

Objective To systematically evaluate the efficacy of treatments for tics and the risks associated with their use. Methods This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology\u27s guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics. Results There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs. Conclusions There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations

Practice Guideline Recommendations Summary: Treatment of Tics in People with Tourette Syndrome and Chronic Tic Disorders

Objective To make recommendations on the assessment and management of tics in people with Tourette syndrome and chronic tic disorders. Methods A multidisciplinary panel consisting of 9 physicians, 2 psychologists, and 2 patient representatives developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine–compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Results Forty-six recommendations were made regarding the assessment and management of tics in individuals with Tourette syndrome and chronic tic disorders. These include counseling recommendations on the natural history of tic disorders, psychoeducation for teachers and peers, assessment for comorbid disorders, and periodic reassessment of the need for ongoing therapy. Treatment options should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered. Treatment options include watchful waiting, the Comprehensive Behavioral Intervention for Tics, and medication; recommendations are provided on how to offer and monitor these therapies. Recommendations on the assessment for and use of deep brain stimulation in adults with severe, treatment-refractory tics are provided as well as suggestions for future research

Trialogue on the number of fundamental constants

This paper consists of three separate articles on the number of fundamental dimensionful constants in physics. We started our debate in summer 1992 on the terrace of the famous CERN cafeteria. In the summer of 2001 we returned to the subject to find that our views still diverged and decided to explain our current positions. LBO develops the traditional approach with three constants, GV argues in favor of at most two (within superstring theory), while MJD advocates zero.Comment: Version appearing in JHEP; 31 pages late

Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease

Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies

Encephalopathy, Hypoglycemia, and Flailing Extremities: A Case of Bilateral Chorea““Ballism Associated with Diabetic Ketoacidosis

Background: Hypo/hyperglycemia is a known cause of chorea and hemiballism. The temporallobes, hippocampus, basal ganglia, and substantia nigra are most susceptible to hypoglycemic changes. Methods: We present a caseof bilateral chorea and bi-ballism accompanied by encephalopathyin the setting of severe hypoglycemia and diabetic ketoacidosis. The patient had brain MRI changes involving both caudate nuclei, temporal lobes, and hippocampi. Discussion: This case demonstrates the basal ganglia's vulnerability to hypoglycemia and the need for cautious evaluation of involuntary movements when they occur in the setting of encephalopathy

A Review of Cognitive Outcomes Across Movement Disorder Patients Undergoing Deep Brain Stimulation

Introduction: Although the benefit in motor symptoms for well-selected patients with deep brain stimulation (DBS) has been established, cognitive declines associated with DBS can produce suboptimal clinical responses. Small decrements in cognition can lead to profound effects on quality of life. The growth of indications, the expansion of surgical targets, the increasing complexity of devices, and recent changes in stimulation paradigms have all collectively drawn attention to the need for re-evaluation of DBS related cognitive outcomes.Methods: To address the impact of cognitive changes following DBS, we performed a literature review using PubMed. We searched for articles focused on DBS and cognition. We extracted information about the disease, target, number of patients, assessment of time points, cognitive battery, and clinical outcomes. Diseases included were dystonia, Tourette syndrome (TS), essential tremor (ET), and Parkinson's disease (PD).Results: DBS was associated with mild cognitive issues even when rigorous patient selection was employed. Dystonia studies reported stable or improved cognitive scores, however one study using reliable change indices indicated decrements in sustained attention. Additionally, DBS outcomes were convoluted with changes in medication dose, alleviation of motor symptoms, and learning effects. In the largest, prospective TS study, an improvement in attentional skills was noted, whereas smaller studies reported variable declines across several cognitive domains. Although, most studies reported stable cognitive outcomes. ET studies largely demonstrated deficits in verbal fluency, which had variable responses depending on stimulation setting. Recently, studies have focused beyond the ventral intermediate nucleus, including the post-subthalamic area and zona incerta. For PD, the cognitive results were heterogeneous, although deficits in verbal fluency were consistent and related to the micro-lesion effect.Conclusion: Post-DBS cognitive issues can impact both motor and quality of life outcomes. The underlying pathophysiology of cognitive changes post-DBS and the identification of pathways underpinning declines will require further investigation. Future studies should employ careful methodological designs. Patient specific analyses will be helpful to differentiate the effects of medications, DBS and the underlying disease state, including disease progression. Disease progression is often an underappreciated factor that is important to post-DBS cognitive issues