Faculty Bibliography

OBJECT: The authors investigated whether the insertion of deep brain stimulation electrodes into the subthalamic nucleus can alter regional brain metabolism in the absence of stimulation. METHODS: Six patients with Parkinson disease (PD) underwent preoperative FDG PET scanning, and again after STN electrode implantation with stimulation turned off. RESULTS: Compared with baseline values, glucose utilization was reduced in the postoperative off-stimulation scans in the putamen/globus pallidus and in the ventral thalamus (p < 0.01), and there was increased metabolism in the sensorimotor cortex and cerebellum (p < 0.005). The expression of a specific PD-related spatial covariance pattern measured in the FDG PET data did not change after electrode implantation (p = 0.36), nor was there a significant change in clinical motor ratings (p = 0.44). Differences in PD-related spatial covariance pattern expression among the patients after electrode implantation did, however, correlate with the number of microelectrode recording trajectories placed during surgery (r = -0.82, p < 0.05). CONCLUSIONS: These findings suggest that electrode implantation can impart a microlesion effect on regional brain function. Nonetheless, these local changes did not cross the threshold of network modulation needed to achieve clinical benefit

We report the successful treatment of an episode of major depression with psychotic features with electroconvulsive therapy (ECT) in a 78-year-old woman with advanced Parkinson disease who had a left subthalamic nucleus deep-brain stimulator (DBS) in place. Electroconvulsive therapy effectively and safely treated the patient's depression without harming the patient or damaging the DBS hardware. We offer additional evidence about the safety and efficacy of electroconvulsive therapy in patients with DBS.

Parkinson's disease (PD) is associated with abnormal activity in spatially distributed neural systems mediating the motor and cognitive manifestations of this disorder. Metabolic PET studies have demonstrated that this illness is characterized by a set of reproducible functional brain networks that correlate with these clinical features. The time at which these abnormalities appear is unknown, as is their relationship to concurrent clinical and dopaminergic indices of disease progression. In this longitudinal study, 15 early stage PD patients (age 58.0 +/- 10.2 years; Hoehn and Yahr Stage 1.2 +/- 0.3) were enrolled within 2 years of diagnosis. The subjects underwent multitracer PET imaging at baseline, 24 and 48 months. At each timepoint they were scanned with [18F]-fluorodeoxyglucose (FDG) to assess longitudinal changes in regional glucose utilization and in the expression of the PD-related motor (PDRP) and cognitive metabolic covariance patterns (PDCP). At each timepoint the subjects also underwent PET imaging with [18F]-fluoropropyl betaCIT (FP-CIT) to quantify longitudinal changes in caudate and putamen dopamine transporter (DAT) binding. Regional metabolic changes across the three timepoints were localized using statistical parametric mapping (SPM). Longitudinal changes in regional metabolism and network activity, caudate/putamen DAT binding, and Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings were assessed using repeated measures analysis of variance (RMANOVA). Relationships between these measures of disease progression were assessed by computing within-subject correlation coefficients. We found that disease progression was associated with increasing metabolism in the subthalamic nucleus (STN) and internal globus pallidus (GPi) (P < 0.001), as well as in the dorsal pons and primary motor cortex (P < 0.0001). Advancing disease was also associated with declining metabolism in the prefrontal and inferior parietal regions (P < 0.001). PDRP expression was elevated at baseline relative to healthy control subjects (P < 0.04), and increased progressively over time (P < 0.0001). PDCP activity also increased with time (P < 0.0001). However, these changes in network activity were slower than for the PDRP (P < 0.04), reaching abnormal levels only at the final timepoint. Changes in PDRP activity, but not PDCP activity, correlated with concurrent declines in striatal DAT binding (P < 0.01) and increases in motor ratings (P < 0.005). Significant within-subject correlations (P < 0.01) were also evident between the latter two progression indices. The early stages of PD are associated with progressive increases and decreases in regional metabolism at key nodes of the motor and cognitive networks that characterize the illness. Potential disease-modifying therapies may alter the time course of one or both of these abnormal networks

Paroxysmal movement disorders are a group of heterogeneous entities that have been categorized based on their most salient features. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, hypnogenic, and exercise-induced. The phenotypic variability of these disorders, coupled with new insights into their possible etiologies, has made the task of classification increasingly problematic. We describe 4 cases that do not fit easily into the current classification scheme, compare them with four others recently described in the literature, and raise the question as to whether they constitute a new subtype

BACKGROUND: Since the Food and Drug Administration approved DBS, there has been a surge in the number of centers providing the procedure. There is currently no consensus regarding appropriate screening procedures, necessary training of individuals providing the therapy, the need for an interdisciplinary team, or guidelines for the management of complications. An increasing number of patients come to experienced DBS centers after unsatisfactory results from DBS surgery. An attempt is made herein to evaluate the reasons for DBS failure in a series of such patients and to make recommendations to improve overall DBS outcomes. OBJECTIVE: To improve outcomes of deep brain stimulation (DBS) surgery by analyzing a series of patients who had suboptimal results from DBS. METHODS: Forty-one consecutive patients complaining of suboptimal results from DBS surgery came to the University of Florida Movement Disorders Center, or to Beth Israel Movement Disorders Center, over a 24-month period. All patients had undergone implantation of DBS devices at outside medical centers. Each patient was evaluated by a movement disorders neurologist, and the complete medical record was reviewed. The DBS device for each patient was interrogated for adverse effects and programmed for maximal benefit. Postoperative imaging studies were evaluated whenever possible. RESULTS: The average age of patients was 63.4 years (range, 49-84 years). The indication for surgery (by record review) included 9 patients with essential tremor, 31 with Parkinson disease, and 1 with dystonia. The diagnoses after referral examination included 5 with essential tremor, 26 with Parkinson disease, 3 with Parkinson disease and dementia, 1 with Parkinson disease and essential tremor, 1 with corticobasal degeneration, 1 with dystonia, 2 with multiple system atrophy, 1 with progressive supranuclear palsy, and 1 with myoclonus. Issues related to inadequate preoperative screening: Thirty (73%) of 41 patients saw a movement disorders specialist prior to DBS implantation. Fourteen (34%) patients had neuropsychological testing, 4 (10%) did not have testing, and in 23 cases (56%), it could not be determined whether or not they were tested. Five (12%) of 41 patients had an inadequate medication trial, and 5 patients (12%) had significant cognitive dysfunction prior to their DBS implantation. Surgical and device-related complications: Nineteen (46%) of 41 patients had suboptimally placed electrodes. Seven electrodes (17%) were replaced with improvement. Three patients' devices had failed due to end of battery life, 2 had infections, and 1 had a fractured lead. Programming and medication adjustments: Seven (17%) of 41 patients had no or poor access to programming. Two patients (5%) moved, and 2 physicians (5%) moved, creating issues with access to care. Eight patients (20%) required local follow-up (they flew to remote centers to have the surgery performed). Fifteen patients (37%) were inadequately programmed and improved significantly with reprogramming. Six patients (15%) experienced partial improvement with reprogramming, and 21 patients (51%) failed to improve despite extensive reprogramming. Thirty patients (73%) benefited from medication changes, 4 (10%) had antidepressants added to their regimens, and 1 (2%) had donepezil hydrochloride added. One patient's carbidopa/levodopa (2%) was restarted after complete discontinuation. Outcomes: With the various postoperative interventions described, 21 (51%) of 41 patients had good outcomes, 6 (15%) had modest clinical improvement, and 14 (34%) did not improve. CONCLUSIONS: With appropriate intervention, 51% of patients who complained of 'failed' DBS procedures ultimately had good outcomes. Thirty-four percent of these patients had persistently poor outcomes despite maximal intervention. This case series provides important insights into reasons for 'DBS failure' and proposes strategies to manage patients with DBS more effectively

In this case study, we describe the symptoms, neurological examination, clinical course, and neuropathology of a patient with progressive supranuclear palsy (PSP). PSP is a relatively uncommon neurodegenerative disorder with many features similar to those of Parkinson's disease. It is characterized by slow motor function, ocular movement abnormalities, dystonia, and cognitive disabilities. PSP is largely a sporadic disorder caused by accumulation of the protein tau in diverse regions of the central nervous system. It is thus classified as one of several tauopathies. The exact cause of the disease remains unknown, and treatment is often limited. The following case provides a framework to explore the manifestations of PSP, as well as the progress made in understanding the nature of this challenging disorder