Atchar Sudhyadhom

REOPERATION FOR SUBOPTIMAL OUTCOMES AFTER DEEP BRAIN STIMULATION SURGERY

OBJECTIVETo examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinsons disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in 1 patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation. METHODSPatients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinsons Disease Questionnaire-39 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery. RESULTSThere were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores. The average improvement across this group of patients was 24.4%. The Parkinsons Disease Questionnaire-39 improved in the areas of mobility (28.18), activities of daily living (14.77), emotion (14.72), stigma (17.61), and discomfort (17.42). The average age of the ET group was 66 years, the disease duration was 29 years, and the average adjusted distance was 6.1 mm. Five ET patients (83.3%) in the cohort had a prereplacement on DBS Tremor Rating Scale and a postreplacement on DBS Tremor Rating Scale with the average improvement of 60.4%. The average age of the dystonia group was 39 years, the average disease duration was 7 years, and the average adjusted lead distance was 6.7 mm. Three patients (75%) with dystonia had prereplacement on DBS Unified Dystonia Rating Scale and postreplacement on DBS Unified Dystonia Rating Scale scores. Across these 3 dystonia patients, the improvement was 12.8%. Clinician Global Impression scale scores (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse) after replacement revealed the following results in patients with PD: 1, 7 patients; 2, 3 patients; 3, 1 patient); with ET (1, 4 patients; 2, 3 patients); and with dystonia (1, 1 patient; 2, 2 patients; 3, 1 patient). The latency from original lead placement to reoperation (repositioning/revision) overall was 28.9 months (range, 2–104 mo); however, in leads referred from outside institutions (n = 11 patients), this latency was 48 months (range, 12–104 mo) compared with leads implanted by surgeons from the University of Florida (n = 11 patients), which was 9.7 months (range, 2–19 mo). The most common clinical history was failure to achieve a perceived outcome; however, history of an asymmetric benefit was present in 4 (18.2%) of 22 patients, and lead migration was present in 3 (13.6%) of 22 patients. CONCLUSIONThere are many potential causes of suboptimal benefit after DBS. Timely identification of suboptimal lead placements followed by reoperation and repositioning/replacement in a subset of patients may improve outcomes.

A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR).

DBS depends on precise placement of the stimulating electrode into an appropriate target region. Image-based (direct) targeting has been limited by the ability of current technology to visualize DBS targets. We have recently developed and employed a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) 3T MRI sequence to more reliably visualize these structures. The FGATIR provides significantly better high resolution thin (1 mm) slice visualization of DBS targets than does either standard 3T T1 or T2-weighted imaging. The T1 subcortical image revealed relatively poor contrast among the targets for DBS, though the sequence did allow localization of striatum and thalamus. T2 FLAIR scans demonstrated better contrast between the STN, SNr, red nucleus (RN), and pallidum (GPe/GPi). The FGATIR scans allowed for localization of the thalamus, striatum, GPe/GPi, RN, and SNr and displayed sharper delineation of these structures. The FGATIR also revealed features not visible on other scan types: the internal lamina of the GPi, fiber bundles from the internal capsule piercing the striatum, and the boundaries of the STN. We hope that use of the FGATIR to aid initial targeting will translate in future studies to faster and more accurate procedures with consequent improvements in clinical outcomes.

A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder

Deep brain stimulation (DBS) of the basal ganglia is an effective treatment for select movement disorders, including Parkinson’s disease, essential tremor and dystonia. Based on these successes, DBS has been explored as an experimental treatment for medication-resistant neuropsychiatric disease. During a multiyear experience employing DBS to treat patients for obsessive compulsive disorder (OCD) we encountered several unanticipated stimulation-induced psychiatric side effects. We present a case of a young woman treated for OCD with DBS of the anterior limb of the internal capsule and nucleus accumbens region, who subsequently manifested a manic episode. We aim to discuss the case details, treatment and potential neuroanatomical underpinnings of this response.

Broca's area and its striatal and thalamic connections: a diffusion-MRI tractography study.

In the recent decades structural connectivity between Brocas area and the basal ganglia has been postulated in the literature, though no direct evidence of this connectivity has yet been presented. The current study investigates this connectivity using a novel diffusion-weighted imaging (DWI) fiber tracking method in humans in vivo. Our findings suggest direct connections between sub-regions of Brocas area and the anterior one-third of the putamen, as well as the ventral anterior nucleus of the thalamus. Thus, we are the first to provide a detailed account of inferred circuitry involving basal ganglia, thalamus, and Brocas area, which would be a prerequisite to substantiate their support of language processing.

Physical activity and neural correlates of aging: A combined TMS/fMRI study

Aerobic exercise has been suggested to ameliorate aging-related decline in humans. Recently, evidence has indicated chronological aging is associated with decreases in measures of interhemispheric inhibition during unimanual movements, but that such decreases may be mitigated by long-term physical fitness. The present study investigated measures of ipsilateral (right) primary motor cortex activity during right-hand movements using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS). Healthy, right-handed participant groups were comprised of 12 sedentary older adults, 12 physically active older adults, and 12 young adults. Active older adults and younger adults evidenced longer ipsilateral silent periods (iSP) and less positive BOLD of ipsilateral motor cortex (iM1) as compared to sedentary older adults. Across groups, duration of iSP from TMS was inversely correlated with BOLD activity in iM1 during unimanual movement. These findings suggest that increased physical activity may have a role in decreasing aging-related losses of interhemispheric inhibition.

Smile and Laughter Induction and Intraoperative Predictors of Response to Deep Brain Stimulation for Obsessive Compulsive Disorder

We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over 2 years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation, some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and p<0.0001 for left brain). In contrast, at contacts where smiles were not observed, mood was negatively correlated with voltage (p=0.0591 for right brain and p=0.0086 for left). Smile and laughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA. The presence of stimulation induced laughter predicted improvement in OCD symptoms at 2 years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with 1 and 2-month postoperative test stimulation and were not observed at subsequent test stimulation sessions. Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more patients are implanted with DBS devices. A larger study is needed to better delineate the relationship between induced intraoperative and postoperative emotional behavior and clinical outcome in patients treated with DBS therapy.

Pedunculopontine Nucleus Stimulation: Where are We Now and What Needs to be Done to Move the Field Forward?

Falls and gait impairment in Parkinson’s Disease (PD) is a leading cause of morbidity and mortality, significantly impacting quality of life and contributing heavily to disability. Thus far axial symptoms, such as postural instability and gait freezing, have been refractory to current treatment approaches and remain a critical unmet need. There has been increased excitement surrounding the surgical targeting of the pedunculopontine nucleus (PPN) for addressing axial symptoms in PD. The PPN and cuneate nucleus comprise the mesencephalic locomotor region, and electrophysiologic studies in animal models and human imaging studies have revealed a key role for the PPN in gait and postural control, underscoring a potential role for DBS surgery. Previous limited studies of PPN deep brain stimulation (DBS) in treating gait symptoms have had mixed clinical outcomes, likely reflect targeting variability and the inherent challenges of targeting a small brainstem structure that is both anatomically and neurochemically heterogeneous. Diffusion tractography shows promise for more accurate targeting and standardization of results. Due to the limited experience with PPN DBS, several unresolved questions remain about targeting and programing. At present, it is unclear if there is incremental benefit with bilateral versus unilateral targeting of PPN or whether PPN targeting should be performed as an adjunct to one of the more traditional targets. The PPN also modulates non-motor functions including REM sleep, cognition, mood, attention, arousal, and these observations will require long-term monitoring to fully characterize potential side effects and benefits. Surgical targeting of the PPN is feasible and shows promise for addressing axial symptoms in PD but may require further refinements in targeting, improved imaging, and better lead design to fully realize benefits. This review summarizes the current knowledge of PPN as a DBS target and areas that need to be addressed to advance the field.

Effects of aerobic fitness on aging-related changes of interhemispheric inhibition and motor performance

Physical fitness has been long associated with maintenance and improvement of motor performance as we age. In particular, measures of psychomotor speed and motor dexterity tend to be higher in physically fit aging adults as compared to their sedentary counterparts. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), we explored the patterns of neural activity that may, in part, account for differences between individuals of varying physical fitness levels. In this study, we enrolled both sedentary and physically fit middle age (40–60) and younger (18–30) adults and measured upper extremity motor performance during behavioral testing. In a follow-up session, we employed TMS and fMRI to assess levels of interhemispheric communication during unimanual tasks. Results show that increased physical fitness is associated with better upper extremity motor performance on distal dexterity assessments and increased levels of interhemispheric inhibition in middle age adults. Further, the functional correlates of changes of ipsilateral activity appears to be restricted to the aging process as younger adults of varying fitness levels do not differ in hemispheric patterns of activity or motor performance. We conclude that sedentary aging confers a loss of interhemispheric inhibition that is deleterious to some aspects of motor function, as early as midlife, but these changes can be mediated by chronic engagement in aerobic exercise.

Evaluation of PC-ISO for Customized, 3D Printed, Gynecologic 192-Ir HDR Brachytherapy Applicators

The purpose of this study was to evaluate the radiation attenuation properties of PC‐ISO, a commercially available, biocompatible, sterilizable 3D printing material, and its suitability for customized, single‐use gynecologic (GYN) brachytherapy applicators that have the potential for accurate guiding of seeds through linear and curved internal channels. A custom radiochromic film dosimetry apparatus was 3D‐printed in PC‐ISO with a single catheter channel and a slit to hold a film segment. The apparatus was designed specifically to test geometry pertinent for use of this material in a clinical setting. A brachytherapy dose plan was computed to deliver a cylindrical dose distribution to the film. The dose plan used an 192Ir source and was normalized to 1500 cGy at 1 cm from the channel. The material was evaluated by comparing the film exposure to an identical test done in water. The Hounsfield unit (HU) distributions were computed from a CT scan of the apparatus and compared to the HU distribution of water and the HU distribution of a commercial GYN cylinder applicator. The dose depth curve of PC‐ISO as measured by the radiochromic film was within 1% of water between 1 cm and 6 cm from the channel. The mean HU was ‐10 for PC‐ISO and ‐1 for water. As expected, the honeycombed structure of the PC‐ISO 3D printing process created a moderate spread of HU values, but the mean was comparable to water. PC‐ISO is sufficiently water‐equivalent to be compatible with our HDR brachytherapy planning system and clinical workflow and, therefore, it is suitable for creating custom GYN brachytherapy applicators. Our current clinical practice includes the use of custom GYN applicators made of commercially available PC‐ISO when doing so can improve the patients treatment. PACS number: none

A Behavioral Manipulation Engages Right Frontal Cortex During Aphasia Therapy

Background. An aphasia treatment was designed to shift laterality from the left to right lateral frontal lobe during word production by initiating word-finding trials with complex left-hand movements. Previous findings indicated successful relateralization. Objective. The current study was designed to ascertain whether the shift was attributable to the left-hand movement. Methods. Using stratified random sampling, 14 subjects were equally divided between Intention (IT) and Control (CT) treatments. CT was identical to IT, except with no left-hand movements. Both treatments trained picture naming (phases 1 and 2) and category-member generation (phase 3), each phase lasting 10 sessions. Functional magnetic resonance imaging of category member generation occurred at pretreatment, posttreatment, and 3-month follow-up. Results. IT shifted lateral frontal activity rightward compared with pretreatment both at posttreatment (t = −2.602, df = 6, P < .05) and 3-month follow-up (t = −2.332, df = 5, P < .05), but CT did not. IT and CT yielded similar changes for all picture-naming and category probes. However, IT patients showed gains for untrained category (t = 3.33, df = 6, P < .01) and picture-naming probes (t = 3.77, df = 5, P < .01), but CT patients did not. Conclusions. The rightward shift in lateral frontal activity for IT was because of the left-hand movements. IT evoked greater generalization than CT.