Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary.

INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

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.

Bilateral Lower Sternocleidomastoid Botulinum Toxin Injections to Address Refractory Anterocollis.

Anterocollis is a type of cervical dystonia characterized by simultaneous and repetitive antagonist muscles contractions, resulting in abnormal neck flexion. It was described with a frequency of 6.8% from 399 patients with diagnosis of cervical dystonia and usually coexists with torticollis and/or laterocollis, as mixed cervical dystonia patterns. Botulinum toxin is usually a practical and effective treatment for cervical dystonia. The target muscles to inject in anterocollis are usually sternocleidomastoid and scalene muscles. There is also a case report suggesting longus collis involvement. Nevertheless, the dosage of the medication in anterocollis is limited by frequent side effects of dysphagia. We described 2 cases of refractory anterocollis. They did not benefit from conventional bilateral upper portion of sternocleidomastoid muscle injections with OnabotulinumtoxinA, but notably improved their symptoms and clinical global impression after switching to injections into bilateral lower portion of sternocleidomastoid muscles, without significant side effects.

A Polysomnographic Study of Parkinson's Disease Sleep Architecture.

Sleep disturbance is a common nonmotor phenomenon in Parkinson's disease (PD) affecting patient's quality of life. In this study, we examined the association between clinical characteristics with sleep disorders and sleep architecture patterns in a PD cohort. Patients underwent a standardized polysomnography study (PSG) in their "on medication" state. We observed that male gender and disease duration were independently associated with obstructive sleep apnea (OSA). Only lower levodopa equivalent dose (LED) was associated with periodic limb movement disorders (PLMD). REM sleep behavior disorder (RBD) was more common among older patients, with higher MDS-UPDRS III scores, and LED. None of the investigated variables were associated with the awakenings/arousals (A/A). Sleep efficiency was predicted by amantadine usage and age, while sleep stage 1 was predicted by dopamine agonists and Hoehn & Yahr severity. The use of MAO-B inhibitors and MDS-UPDRS part III were predictors of sleep stages 2 and 3. Age was the only predictor of REM sleep stage and gender for total sleep time. We conclude that sleep disorders and architecture are poorly predictable by clinical PD characteristics and other disease related factors must also be contributing to these sleep disturbances.

Novel targets and stimulation paradigms for deep brain stimulation.

Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

Atrophy and other potential factors affecting long term deep brain stimulation response: a case series.

OBJECTIVE: To describe three DBS cases which presented with new side effects or loss of benefit from stimulation after long-term follow-up and to discuss the potential contributing factors. METHODS: A University of Florida (UF) database (INFORM) search was performed, identifying three patients, two Parkinson's disease (PD) and one Essential Tremor (ET), with an unexpected change in long-term programming thresholds as compared to initial evaluation. Clinical follow-up, programming, imaging studies, and lead measurements were reviewed. The UF Institutional Review Board (IRB) approved this study. RESULTS: A substantial increase in the 3rd ventricular width (120%), Evans index (6%), ventricular index (5%), and cella media index (17%) was uncovered. A change in thresholds across lead contacts with a decrease in current densities as well as a relative lateral change of lead location was also observed. Hardware-related complications, lead migration, and impedance variability were not identified. CONCLUSIONS: Potential factors contributing to long-term side effects should be examined during a DBS troubleshooting assessment. Clinicians should be aware that in DBS therapy there is delivery of electricity to a changing brain, and atrophy may possibly affect DBS programming settings as part of long-term follow-up.

Intraoperative smile in a multiple sclerosis patient with medication-refractory tremor.

Deep brain stimulation has been utilized to improve disease symptoms in patients with Parkinson's disease, dystonia, essential tremor, and other neuropsychiatric syndromes such as depression and obsessive compulsive disorder. Deep brain stimulation has also been observed to improve tremor for select patients with multiple sclerosis. During intraoperative stimulation in these multiple sclerosis patients, researchers have observed a wide spectrum of motor and sensory phenomena, but no stimulation-induced emotional responses have been reported. We detailed intraoperative smiling associated with stimulation of the ventralis oralis anterior/ventralis oralis posterior border region of the left thalamus.  A single patient with medication-resistant multiple sclerosis tremor experienced smiling, laughing, and subjective euphoria during intraoperative stimulation of the left thalamus. Specifically, during intraoperative stimulation of the left thalamic ventralis oralis anterior border, the patient developed a contralateral smile which progressed to a bilateral smile and was accompanied by a feeling of subjective happiness. The smile habituated in approximately 60 seconds and it was reproducible on a repeat stimulation. The patient could subjectively feel the facial movement, and, at higher voltages, the movement was described as a pulling sensation. Stimulation of the anterior ventralis oralis anterior border of the left thalamus in an multiple sclerosis patient produced a unilateral smile that rapidly developed into a bilateral smile accompanied by euphoria. There were presumed capsular side effects at higher voltages. The exact mechanism by which stimulation of the thalamus produced a smile and mood elevation is unknown, but we speculate that the smile could be induced by stimulation of corticobulbar fibers arising from the caudal cingulate motor area connecting the contralateral facial nerve nucleus.

Unilateral thalamic deep brain stimulation in essential tremor demonstrates long-term ipsilateral effects.

INTRODUCTION: Deep Brain Stimulation (DBS) of thalamus in essential tremor (ET) is effective for the treatment of contralateral tremors. Bilateral DBS controls tremors on both sides but is associated with increased morbidity and risks. We evaluated if unilateral surgery had ipsilateral benefits on tremors and thus could be a potentially safer alternative to bilateral DBS. METHODS: Medication refractory ET patients undergoing unilateral thalamic DBS were included and longitudinally followed. Tremor rating scale was used to record total motor, arm tremor and activities of daily living (ADL) scores at baseline, six months and at last visit (three or more years after surgery). Postoperative scores were recorded with DBS turned OFF and ON. RESULTS: Twenty-two patients with a mean follow-up 3.4 ± 0.14 years were enrolled. When baseline scores were compared to scores with the DBS turned ON, significant improvements were noted in total tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the contralateral side at six months and at the last visit of follow-up (all p < 0.05). Ipsilateral arm tremor (∼56%) improvements were milder compared to the contralateral side (∼73%) tremors. CONCLUSION: Unilateral thalamic DBS in ET demonstrates significant long-term benefits for ipsilateral arm tremors and can be offered to higher risk and to select patients.

Emerging opportunities for serotypes of botulinum neurotoxins.

BACKGROUND: Two decades ago, botulinum neurotoxin (BoNT) type A was introduced to the commercial market. Subsequently, the toxin was approved by the FDA to address several neurological syndromes, involving muscle, nerve, and gland hyperactivity. These syndromes have typically been associated with abnormalities in cholinergic transmission. Despite the multiplicity of botulinal serotypes (designated as types A through G), therapeutic preparations are currently only available for BoNT types A and B. However, other BoNT serotypes are under study for possible clinical use and new clinical indications; OBJECTIVE: To review the current research on botulinum neurotoxin serotypes A-G, and to analyze potential applications within basic science and clinical settings; CONCLUSIONS: The increasing understanding of botulinal neurotoxin pathophysiology, including the neurotoxin's effects on specific neuronal populations, will help us in tailoring treatments for specific diagnoses, symptoms and patients. Scientists and clinicians should be aware of the full range of available data involving neurotoxin subtypes A-G.

Pielotac como alternativa en el diagnóstico de la urolitiasis: experiencia en el hospital clínico UC / UHCT as an alternative in the diagnosis of urolithiasis: experience in UC clinical hospital

La utilización de la Tomografía Helicoidal Sin Contraste (PIELOTAC) para el diagnóstico de la urolitiasis es hoy en día una alternativa vigente y que aparece llevar a terapias más oportunas y efectivas. El objetivo de este trabajo es evaluar la experiencia de nuestra institución desde la incorporación rutinaria del Piolotac para diagnóstico de la urolitiasis, comparando con cifras históricas locales en las que el manejo diagnóstico se realizó con Pielografía IV como primer examen. Revisión retrospectiva de las fichas de urgencia entre enero a mayo del 2001, extrayendo aquellos pacientes que consultaron por litiasis urinaria. De estas se obtuvieron valores relacionados con edad, sexo, antecedentes clínicos, historia clínica actual, uso del Pielotac en su intento diagnóstico, número, tamaño ubicación de la litiasis y grado de repercusión en el sistema urinario, tiempo transcurrido al tratamiento sea médico y/o quirúrgico, así como también, la efectividad de éste. En un total de 111 pacientes que consultaron al servicio de urgencia, en su mayoría del sexo masculino (55 por ciento9, se logró obtener la confirmación de la urolitiasis a través del Pielotac. En su mayoría resultaron ser hombres con litiasis de ubicación uretral distal con escaso compromiso de dilatación del sistema urinario y que en un 93 por ciento fueron resueltas dentro de las 24 hrs. posterior al ingreso del paciente, con muy buena respuesta. En un 1,5 por ciento se requirió un nuevo intento de litotripsia. En un 12,6 por ciento de los pacientes se pudo diagnosticar otras entidades como diagnóstico diferencial, de ellas 1 pacientes se les diagnóstico enfermedad diverticular complicada, en 2 apendicitis aguda, un tumor renal, 4 tumores ováricos (teratomas quísticos) y 6 pielonefritis agudas. La Pielotac es hoy un examen que guarda cualidades técnicas que lo hacen ser de gran ayuda en la urolitiasis y a veces como diagnóstico diferencial de otras patologías que debieron ser resueltas quirúrgicamente. Sin embargo, sigue siendo de alto costo y no accesible en todo recinto hospitalario.