Parkinson Disease: Neimat JS

Remple MS, Sarpong Y, Neimat JS. · Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · Expert Rev Neurother. · Pubmed #18505355 No free full text.

Abstract: Despite the continued refinement of medical and surgical therapies, the treatment of Parkinson's disease (PD) remains challenging. Current treatment strategies are largely focused on managing the motor symptoms of the disease, either by dopamine-based medications or, in advanced stages, by the application of deep brain stimulation to more stably alter the function of the basal ganglia. Important advances have been made in the last decade, but unfortunately a number of the motor symptoms of late-stage PD remain poorly treated, and while currently available therapies address the symptoms of the disease, they fail to alter the course of the disease itself. This has spurred basic and clinical exploration on a number of fronts. Several centers have examined novel stimulation targets to treat refractory symptoms of gait difficulty and axial imbalance. Basic and clinical researchers are examining whether the use of deep brain stimulation might slow the progress of the disease and thus be a useful neuroprotective therapy if initiated earlier in the progression of the disease. An expanded understanding of the genetic and cellular events that underlie PD has led some researchers to explore the use of neurotrophic factors or genetic restoration to preserve threatened neuronal populations. Finally, there has been much research on the use of fetal mesencephalic or stem cell populations to restore dopaminergic function. In this report, we will examine each of these potential new surgical therapies and the promise they may hold for the future treatment of PD.

Yu H, Neimat JS. · Department of Neurological Surgery, Vanderbilt University, Nashville, Tennessee 37232, USA. · Neurotherapeutics. · Pubmed #18164481 No free full text.

Abstract: It has been understood, for some time, that modulation of deep brain nuclei within the basal ganglia and thalamus can have a therapeutic effect in patients with movement disorders. Because of its reversibility and adjustability, deep brain stimulation (DBS) has largely come to replace traditional ablation procedures. The clinical effects of DBS vary, depending both on the target being stimulated and on the parameters of stimulation. Both aspects are currently the subject of substantial research and discovery. The most common targets for DBS treatment include the subthalamic nucleus for the treatment of advanced Parkinson's disease, the ventral intermediate nucleus of the thalamus for the treatment of medically refractory essential tremor, and the globus pallidus interna for the treatment of both cervical and generalized dystonias and Parkinson's disease. We review the current indications, targets, outcomes, and general procedure of DBS for essential tremor, Parkinson's disease, and dystonia.

Hodaie M, Neimat JS, Lozano AM. · Division of Neurosurgery, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Canada. · Neurosurgery. · Pubmed #17228250 No free full text.

Abstract: For several decades, the clinical study of Parkinson's disease has driven an increasingly sophisticated understanding of the dopaminergic system and its complex role in modulating motor behavior. This article reviews salient areas of research in this field, commencing with the molecular biology of the development of the mesencephalic dopaminergic system. We then discuss events thought to be crucial in the cellular and molecular pathology of Parkinson's disease, proposed mechanisms of cell death, and relevant toxin models. These advancements are used as a template to review emerging therapeutic techniques, including neuroprotection strategies, surgical treatment of trophic factors, gene therapy, and neural transplantation.

Neimat JS, Hamani C, Lozano AM. · Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada. · Expert Rev Neurother. · Pubmed #16466317 No free full text.

Abstract: Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Williams ZM, Neimat JS, Cosgrove GR, Eskandar EN. · Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, ACC-021, Boston, MA 02114, USA. · Exp Brain Res. · Pubmed #15635456 No free full text.

Abstract: Current models of basal ganglia function suggest that some manifestations of Parkinson disease (PD) arise from abnormal activity and decreased selectivity of neurons in the subthalamic nucleus (STN) and globus pallidus internus (Gpi). Our goal was to examine the timing and direction selectivity of neuronal activity relative to visually guided movements in the STN and Gpi of patients with PD. Recordings were made from 152 neurons in the STN and 33 neurons in the Gpi of awake subjects undergoing surgery for PD. Corresponding EMG data were obtained for half the cells. We employed a structured behavioral task in which the subjects used a joystick to guide a cursor to one of four targets displayed on a monitor. Each direction was tested over multiple trials. Movement-related modulation of STN activity began on average 264+/-10 ms before movement initiation and 92+/-13 ms before initial EMG activity, while modulation of Gpi activity began 204+/-21 ms before overt movement initiation. In the STN, 40% of cells demonstrated perimovement activity, and of these 64% were directionally selective. In Gpi, 45% of cells showed perimovement activity of which 80% were selective. In both nuclei, directionally selective cells had significantly lower baseline firing rates than nonselective cells (41+/-5 vs 59+/-4 spikes/s in STN, and 50+/-9 vs 74+/-15 spikes/s in Gpi). These results suggest that STN activity occurs earlier than previously reported, and that higher neuronal firing rates maybe associated with decreased direction selectivity in PD patients.