Pallidal deep brain stimulation and intraoperative neurophysiology for treatment of poststroke hemiballism.

Deep brain stimulation is a recognized and effective treatment for several movement disorders. Nevertheless, the efficacy of this intervention on abnormal movements secondary to structural brain pathologies is less consistent. In this report, we describe a case of hemiballism-hemichorea due to a peripartum ischemic stroke-treated with deep brain stimulation of the globus pallidus internus. Patient observed marked improvement in her symptoms at long-term follow-up. Neurophysiologic data revealed lower globus pallidus internus firing rates compared to other hyperkinetic disorders. Pallidal deep brain stimulation is a plausible option for medically refractory hemiballism-hemichorea and cumulative data from multiple centers may be used to fully evaluate its efficacy.

High-Intensity Ultrasound Treatment for Vincristine-Induced Neuropathic Pain.

BACKGROUND: Vincristine is a commonly used chemotherapeutic agent that results in debilitating untreatable peripheral neuropathy. OBJECTIVE: To determine the effects of pulsed high-intensity focused ultrasound (HIFU) on sensory thresholds in a validated vincristine-induced neuropathy (VIN) rodent model. METHODS: VIN was induced and mechanical allodynia was confirmed by nociceptive testing. von Frey fibers and Randall-Sellito test were used as measures of innocuous and noxious mechanical thresholds, respectively, and the hot plate test for thermal thresholds. Tests were performed before VIN, after 2 wk of vincristine, at 24, 48, 72, and 120 h after HIFU applied to the left L5 dorsal root ganglia at 3 Watts for 3 min. Comparisons were made between a VIN cohort who underwent HIFU, a VIN cohort who underwent sham HIFU, and naïve rodents who underwent HIFU. RESULTS: VIN HIFU rats had significantly increased mechanical thresholds at 24 h (P < .001), 48 h (P = .008), 72 h (P = .003), and 120 h (P = .03) after treatment, when compared to pre-HIFU thresholds. Furthermore, at 24 and 48 h following treatment, VIN HIFU rats had significantly higher innocuous and noxious mechanical thresholds and thermal thresholds than VIN sham HIFU rats (P < .001). Thresholds were not altered in naïve rodents who underwent HIFU. Histological data of L5 dorsal root ganglia of VIN HIFU rats suggest that transient cellular edema resolves by 48 h. CONCLUSION: Our data suggest that HIFU increases mechanical and thermal thresholds in VIN rodents. Whether HIFU can preclude the development of reduced thresholds in the VIN model warrants further study.

Effect of Eye Opening on Single-Unit Activity and Local Field Potentials in the Subthalamic Nucleus.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in Parkinson's disease (PD). We investigate the effect of eye opening on neuronal activity and local field potentials (LFPs) in the STN. METHODS: We prospectively enrolled 25 PD patients undergoing STN DBS in our institution. During DBS, single-unit activity (SUA) and LFPs were measured when eyes were open and closed. As movement is known to result in changes in LFPs, we tested response to eye opening in the presence and absence of movement. RESULTS: Neither eye state nor arm movement has a significant influence on SUA recordings. There is a statistically significant interaction between eye state and arm movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open (p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN theta LFP oscillations decrease when eyes are open compared to closed, irrespective of movement status (p < 0.05). DISCUSSION: STN activity is influenced by eye state and arm movement. It is unclear whether this is attributed to a change in the STN's role in oculomotor control or from a change in attentional state. Understanding how physiologic normal activity alters neural activity is critical for the optimization of DBS therapy, particularly in closed-loop neuromodulation.

Evaluation of Quantitative Measurement Techniques for Head Tremor With Thalamic Deep Brain Stimulation.

BACKGROUND: Ventralis intermedius thalamic deep brain stimulation (VIM DBS) has shown to be safe and effective for medically refractory essential tremor (ET). We evaluate the use of quantitative tremor measurement methods for head tremor in ET using a "smart" hat and a smartphone application. METHODS: We enrolled 13 ET patients who previously underwent VIM DBS. Head and arm tremor was measured ON and OFF stimulation using the clinical gold standard Fahn-Tolosa-Marin Tremor Rating Scale (TRS). Results were then compared to two quantitative measurement techniques: Lift Pulse (smartphone application) and modified Nizet (adapted laser point measurement from Nizet et al.). Spearman's rank correlation was used to compare tremor severity and improvement on stimulation using TRS and quantitative methods to measure tremor. RESULTS: Lift Pulse tremor severity measurement significantly correlated with TRS for head (ρ = 0.53, p < 0.01) and arm tremor (ρ = 0.49, p < 0.01). Modified Nizet tremor severity measurement significantly correlated with TRS for head (ρ = 0.83, p < 0.001) and arm tremor (ρ = 0.50, p < 0.01). Inter-method correlation for head tremor severity was significant (ρ = 0.45, p < 0.05). Lift Pulse tremor improvement measurement significantly correlated with TRS for arm tremor (ρ = 0.56, p < 0.05). Modified Nizet tremor improvement measurement significantly correlated with TRS for head tremor (ρ = 0.53, p < 0.01). DISCUSSION: Our results show that Lift Pulse and modified Nizet are both effective techniques to quantitatively measure head and arm tremor severity. We also show the utility of a "smart" hat to measure head tremor. Modified Nizet technique is more effective for measuring head tremor, while Lift Pulse is an effective measure of tremor severity, especially arm tremor improvement.

A Single Center Prospective Observational Study of Outcomes With Tonic Cervical Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation (SCS) has been a valuable resource for the treatment of chronic, nonmalignant pain that persists in the face of maximal medical management. A recent study demonstrated efficacy of cervical SCS in a multicenter registry. Here, in our single center study, we are able to delve into patient specifics, explore outcomes with percutaneous vs. paddle implants, and examine impact of patient symptomatology. METHODS: We prospectively collected data on subjects who underwent cervical SCS via numeric rating scale (NRS), McGill Pain Questionnaire, Oswestry Disability Index (ODI), and Beck Depression Inventory. Subjects completed this battery pre-operatively, at six months and at one year. Data were analyzed via repeated measures ANOVA, bivariate correlation analysis, and paired t-tests. RESULTS: In 30 consecutive subjects, 24 had a complete data set. The diagnosis was failed neck surgery syndrome (13%), Complex regional pain syndrome (29%), and neuropathic pain (58%). Compared with baseline, NRS score significantly improved at six months (p = 0.021) and one year (p = 0.047). ODI score also improved at one year (p = 0.009). At both six months and one year, subjects with percutaneous implants reported significantly less disability on ODI (p = 0.016 and 0.034, respectively), as compared with those who received paddle implants. There was no difference in NRS score or any other outcome measure based on type of implant. Diagnosis or region of pain did not correlate with any measure of outcome. DISCUSSION: We demonstrate that neck and arm pain can be improved with cervical SCS at six month and one-year follow-ups. Both percutaneous and paddle implants have benefit. We tend to place percutaneous implants for radicular pain and retrograde C1-2 paddles for axial pain that is ineffectively treated during the trial.

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson's Disease Patients.

BACKGROUND: Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). OBJECTIVE: In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. METHODS: We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. RESULTS: In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). DISCUSSION: Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits.

Hyperhidrosis associated with subthalamic deep brain stimulation in Parkinson's disease: Insights into central autonomic functional anatomy.

INTRODUCTION: There is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. OBJECTIVE: To describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. METHODS: We retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. RESULTS: Unilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. CONCLUSION: Stimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN.

The Role of Invasive Pain Management Modalities in the Treatment of Chronic Pain.

Invasive analgesic therapies provide an alternative to medical management of chronic pain. With the increasing incidence of chronic pain not only in the United States but worldwide, more therapies have evolved to address the growing need for pain relief options. These therapies include spinal injections, nerve blocks, radiofrequency ablation, neurostimulation, and intrathecal drug delivery.

The Effect of High-Frequency Stimulation on Sensory Thresholds in Chronic Pain Patients.

BACKGROUND: High-frequency stimulation (HFS) has recently gained attention as an alternative to parameters used in traditional spinal cord stimulation (SCS). Because HFS is paresthesia free, the gate theory of pain control as a basis of SCS has been called into question. The mechanism of action of HFS remains unclear. OBJECTIVE: We compare the effects of HFS and traditional SCS on quantitative sensory testing parameters to provide insight into how HFS modulates the nervous system. METHODS: Using quantitative sensory testing, we measured thermal detection and pain thresholds and mechanical detection and pressure pain thresholds, as well as vibratory detection, in 20 SCS patients off stimulation (OFF), on traditional stimulation (ON) and on HFS in a randomized order. RESULTS: HFS significantly increased the mechanical detection threshold compared to OFF stimulation (p < 0.001) and traditional SCS (p = 0.01). Pressure pain detection and vibratory detection thresholds also significantly increased with HFS compared to ON states (p = 0.04 and p = 0.01, respectively). In addition, HFS significantly decreased 10- and 40-gram pinprick detection compared to OFF states (both p = 0.01). No significant differences between OFF, ON and HFS states were seen in thermal and thermal pain detection. CONCLUSION: HFS is a new means of modulating chronic pain. The mechanism by which HFS works seems to differ from that of traditional SCS, offering a new platform for innovative advancements in treatment and a greater potential to treat patients by customizing waveforms.

Successful use of high-frequency spinal cord stimulation following traditional treatment failure.

INTRODUCTION: High-frequency spinal cord stimulation (HFSCS) offers an alternative treatment for chronic refractory pain syndromes nonresponsive to traditional spinal cord stimulation (SCS). Following the conflicting findings of preliminary HFSCS clinical studies performed at 5-10 kHz, this study is the first to report successful clinical usage of 1-kHz frequency SCS with a standard generator. PATIENTS: We used HFSCS in 2 patients who had inadequate relief with traditional SCS. Patient 1 was initially programmed at 40 Hz and a pulse width of 330 µs with bipolar stimulation. After multiple setting adjustments with inadequate pain relief, the patient was reprogrammed to HFSCS at settings of 1.15 kHz, 120 µs, and 5 V. Patient 2 was initially programmed at a frequency of 1.2 kHz and a pulse width of 120 µs, which she favored over the standard setting of 40 Hz and 390 µs pulse width. HFSCS provided optimal pain alleviation and increased quality of life for both patients. CONCLUSIONS: HFSCS at the frequency of 1 kHz offers a new tool for treatment of chronic pain in patients with traditional stimulation settings. Furthermore, most standard SCS batteries are capable of delivering stimulation in this frequency range.

The time of day effects of warm temperature on flowering time involve PIF4 and PIF5.

Warm temperature promotes flowering in Arabidopsis thaliana and this response involves multiple signalling pathways. To understand the temporal dynamics of temperature perception, tests were carried out to determine if there was a daily window of enhanced sensitivity to warm temperature (28 °C). Warm temperature applied during daytime, night-time, or continuously elicited earlier flowering, but the effects of each treatment were unequal. Plants exposed to warm night (WN) conditions flowered nearly as early as those in constant warm (CW) conditions, while treatment with warm days (WD) caused later flowering than either WN or CW. Flowering in each condition relied to varying degrees on the activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes. The combination of signalling pathways involved in flowering depended on the time of the temperature cue. WN treatments caused a significant advance in the rhythmic expression waveform of CO, which correlated with pronounced up-regulation of FT expression, while WD caused limited changes in CO expression and no stimulation of FT expression. WN- and WD-induced flowering was partially CO independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The double mutant was also late flowering in control conditions. In addition, WN conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the PIF4 and PIF5 transcription factors promote flowering by at least two means: inducing FT expression in WN and acting outside of FT by an unknown mechanism in WD.