Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine.

PURPOSE: Transcranial magnetic stimulation (TMS) is a neurophysiological technique with a long established pedigree of safety, tolerability, and efficacy. Initially TMS was used to study the function of the cerebral cortex, but it has now become a treatment for migraine, one of the most common and debilitating neurological conditions. In this review we discuss the scientific background and development of the technique. We explore its application for the treatment of migraine and ponder the possible mechanisms of action in this most common neurological condition. OVERVIEW: The generation of brief magnetic pulses by a suitable coil can induce electrical fields in the body. When applied to the cerebral cortex, currents are painlessly induced in cortical neurons. These currents can lead to neuronal depolarization and may influence cortical excitability by means that are as yet not fully understood. This ability to modulate cortical excitability has been exploited as a treatment for migraine with aura. Aura is implicated in the pathophysiology of migraine. Experimental studies have shown that transcranial magnetic pulses can block waves of cortical spreading depression - the experimental equivalent of migrainous aura. DISCUSSION: Migraine is a debilitating condition characterized by headache, nausea, and sensory hypersensitivity. It may affect up to 15% of the population, yet current drug treatments are often poorly tolerated. Clinical studies have shown that TMS is an effective treatment for migraine. In addition, it has the added advantages of being safe and well tolerated by patients.

Sensory Barrage Stimulation in the Treatment of Elbow Spasticity: A Crossover Double Blind Randomized Pilot Trial.

OBJECTIVE: To assess the feasibility of using a novel form of multichannel electrical stimulation, termed Sensory Barrage Stimulation (SBS) for the treatment of spasticity affecting the elbow flexor muscles and to compare this with conventional single-channel TENS stimulation. MATERIALS AND METHODS: Altogether ten participants with spasticity of the flexor muscles of the elbow of Grade 2 or above on the Modified Ashworth Scale (MAS) were recruited to this crossover double blind randomized trial. The participants received two intervention sessions (SBS and TENS), one week apart in a randomized order. Both interventions were applied over the triceps brachii on the affected arm for a duration of 60 minutes. Spasticity was measured using the MAS. Secondary outcome measures were self-reported change in spasticity, measured on a visual analog scale (VAS, 0-100), and therapist-rated strength of elbow extension and strength of elbow flexion. Measurements were taken immediately before each intervention was applied, immediately after the intervention, and one hour after the intervention. RESULTS: Immediately after stimulation spasticity showed a significant reduction for both TENS and SBS groups assessed by MAS -0.9 ± 0.2 vs. -1.1 ± 0.2 and by VAS -15 ± 3 vs. -31 ± 8. For SBS this improvement in MAS was still present at one hour after the stimulation, but not for TENS. Altogether seven SBS responders and four TENS responders were identified. CONCLUSIONS: This study demonstrates the feasibility and practicality of applying the new concept of SBS. Promising results indicate it causes a reduction in spasticity.

Presser - the forgotten story.

OBJECTIVE: Regina v Presser [1958] VR 45, is the most seminal case regarding fitness to plead for accused persons in Australia and New Zealand. It is not widely understood that Presser was a 14-year-old boy with intellectual disability. We aim to describe a clearer narrative regarding Edward John Presser. METHOD: Review of attainable newspaper reports framed within an historical context of fitness and relevant case law. RESULTS: Presser's narrative is described in greater detail than previously understood by clinicians and lawyers. Ramifications for fitness assessment are discussed including doli incapax and human rights considerations. CONCLUSIONS: The Presser criteria are widely applied; however, the case involved a 14-year-old boy with intellectual disability. Greater awareness of Presser's narrative assists clinicians providing expert evidence regarding fitness to plead for adolescents and persons with intellectual disability.

Feasibility study of a take-home array-based functional electrical stimulation system with automated setup for current functional electrical stimulation users with foot-drop.

OBJECTIVE: To investigate the feasibility of unsupervised community use of an array-based automated setup functional electrical stimulator for current foot-drop functional electrical stimulation (FES) users. DESIGN: Feasibility study. SETTING: Gait laboratory and community use. PARTICIPANTS: Participants (N=7) with diagnosis of unilateral foot-drop of central neurologic origin (>6mo) who were regular users of a foot-drop FES system (>3mo). INTERVENTION: Array-based automated setup FES system for foot-drop (ShefStim). MAIN OUTCOME MEASURES: Logged usage, logged automated setup times for the array-based automated setup FES system and diary recording of problems experienced, all collected in the community environment. Walking speed, ankle angles at initial contact, foot clearance during swing, and the Quebec User Evaluation of Satisfaction with Assistive Technology version 2.0 (QUEST version 2.0) questionnaire, all collected in the gait laboratory. RESULTS: All participants were able to use the array-based automated setup FES system. Total setup time took longer than participants' own FES systems, and automated setup time was longer than in a previous study of a similar system. Some problems were experienced, but overall, participants were as satisfied with this system as their own FES system. The increase in walking speed (N=7) relative to no stimulation was comparable between both systems, and appropriate ankle angles at initial contact (N=7) and foot clearance during swing (n=5) were greater with the array-based automated setup FES system. CONCLUSIONS: This study demonstrates that an array-based automated setup FES system for foot-drop can be successfully used unsupervised. Despite setup's taking longer and some problems, users are satisfied with the system and it would appear as effective, if not better, at addressing the foot-drop impairment. Further product development of this unique system, followed by a larger-scale and longer-term study, is required before firm conclusions about its efficacy can be reached.

Biophysical determinants of transcranial magnetic stimulation: effects of excitability and depth of targeted area.

Safe and effective transcranial magnetic stimulation (TMS) requires accurate intensity calibration. Output is typically calibrated to individual motor cortex excitability and applied to nonmotor brain areas, assuming that it captures a site nonspecific factor of excitability. We tested this assumption by correlating the effect of TMS at motor and visual cortex. In 30 participants, we measured motor threshold (MT) and phosphene threshold (PT) at the scalp surface and at coil-scalp distances of 3.17, 5.63, and 9.03 mm. We also modeled the effect of TMS in a simple head model to test the effect of distance. Four independent tests confirmed a significant correlation between PT and MT. We also found similar effects of distance in motor and visual areas, which did not correlate across participants. Computational modeling suggests that the relationship between the effect of distance and the induced electric field is effectively linear within the range of distances that have been explored empirically. We conclude that MT-guided calibration is valid for nonmotor brain areas if coil-cortex distance is taken into account. For standard figure-of-eight TMS coils connected to biphasic stimulators, the effect of cortical distance should be adjusted using a general correction factor of 2.7% stimulator output per millimeter.

The role of the cerebellum in sub- and supraliminal error correction during sensorimotor synchronization: evidence from fMRI and TMS.

Our ability to interact physically with objects in the external world critically depends on temporal coupling between perception and movement (sensorimotor timing) and swift behavioral adjustment to changes in the environment (error correction). In this study, we investigated the neural correlates of the correction of subliminal and supraliminal phase shifts during a sensorimotor synchronization task. In particular, we focused on the role of the cerebellum because this structure has been shown to play a role in both motor timing and error correction. Experiment 1 used fMRI to show that the right cerebellar dentate nucleus and primary motor and sensory cortices were activated during regular timing and during the correction of subliminal errors. The correction of supraliminal phase shifts led to additional activations in the left cerebellum and right inferior parietal and frontal areas. Furthermore, a psychophysiological interaction analysis revealed that supraliminal error correction was associated with enhanced connectivity of the left cerebellum with frontal, auditory, and sensory cortices and with the right cerebellum. Experiment 2 showed that suppression of the left but not the right cerebellum with theta burst TMS significantly affected supraliminal error correction. These findings provide evidence that the left lateral cerebellum is essential for supraliminal error correction during sensorimotor synchronization.

The ECLiPSE Procedure as an Alternative to Mastopexy following Implant Removal.

With the rise in number of breast implant removals for a variety of indications, strategies to improve aesthetic outcomes, while minimizing scars and operating time, will prove to be of benefit. We present here a novel periareolar sickle skin excision as a good option for women with mild to moderate ptosis and central loss of breast volume following implant removal/capsulectomy. METHODS: The ECLiPSE (Explant, Capsulectomy, Lift using Periareolar Sickle skin Excision) was utilized in 53 patients with a median follow-up of 24 weeks. RESULTS: The majority of these patients had breast implants for cosmetic augmentation and the most common indication for implant removal was capsular contracture (n = 47, 88.7%). Forty-six patients (86.8%) scored a high or very high satisfaction with the outcome of the procedure. CONCLUSION: We believe that the ECLiPSE procedure is a useful option that can produce a reasonable aesthetic outcome following implant removal/capsulectomy while minimizing visible scarring.

The Reversed Glove Sleeve: A Readily Available and Cost-effective Way to Achieve "No Touch" Breast Implant Insertion.

The reversed glove sleeve technique is a simple, available, reproducible, and cost-effective method of achieving "no touch" breast implant insertion. It allows a new glove to be used for each side, thus reducing the risk of contamination by reusing a sleeve/funnel for the subsequent implant insertion. The link between bacterial contamination of breast implants and capsular contracture is established. Further prospective evaluation of this technique is underway to show if there is benefit in reducing the risk of capsular contracture.

Treatment of Tinnitus Using Theta Burst Based Repetitive Transcranial Magnetic Stimulation-A Single Blinded Randomized Control Trial.

OBJECTIVE: To determine whether theta burst repetitive transcranial magnetic stimulation is an effective treatment for chronic tinnitus compared with a control stimulus. STUDY DESIGN: A two-arm, single-blind, randomized controlled trial comparing an active treatment group to a placebo control group. SETTING: Neurotology department of a tertiary referral center. PATIENTS: Forty new and existing patients with chronic unilateral or bilateral tinnitus were recruited from specialist hearing and balance clinics. INTERVENTIONS: The subjects were randomized into two groups representing the treatment and sham subcategories. Two 40 second trains, 15 minutes apart of transcranial stimulation was provided using a super rapid stimulator (2.2. Tesla, Magstim Inc., Wales, UK) using a circular delivery coil. Treatment was provided over 5 consecutive days. MAIN OUTCOME MEASURE: Tinnitus functional index (TFI) scores were recorded before treatment, immediately after treatment, 2 weeks, and at 4 weeks following treatment and compared. RESULTS: TFI scores were analyzed using the Shapiro-Wilk test and found to be normally distributed. A paired Student t test was then performed. Both the active treatment group and control group had a significant improvement in their TFI scores following treatment; however, there was no significant difference between active treatment and sham treatment groups. CONCLUSION: This study demonstrated a significant placebo effect following treatment with sham therapy and may suggest that repetitive transcranial magnetic stimulation does not have a therapeutic use in treating chronic tinnitus.

A finite element model to identify electrode influence on current distribution in the skin.

Discomfort experienced during surface functional electrical stimulation (FES) is thought to be partly a result of localized high current density in the skin underneath the stimulating electrode. This article describes a finite element (FE) model to predict skin current density distribution in the region of the electrode during stimulation and its application to the identification of electrode properties that may act to reduce sensation. The FE model results show that the peak current density was located in an area immediately under the stratum corneum, adjacent to a sweat duct. A simulation of surface FES via a high-resistivity electrode showed a reduction in this peak current density, when compared to that with a low-resistivity electrode.

Reducing the sensation of electrical stimulation with dry electrodes by using an array of constant current sources.

Hydrogel electrodes are commonly used for functional and other electrical stimulation applications since the hydrogel layer has been shown to considerably reduce the perception of stimulation compared to dry electrodes. However, these hydrogel electrodes must be changed regularly as they dry out or become contaminated with skin cells and sweat products, thus losing their adhesiveness and resistive properties. Dry electrodes are longer lasting but are more uncomfortable due to unequal current distribution (current hogging). We hypothesise that if current through a dry electrode is equally shared amongst an array of small sub-electrodes, current hogging and thus the sensitivity perceived due to stimulation will be reduced. We constructed an 8 × 8 array of millimetre sized dry electrodes that could either be activated as individual current sources, or together as one large source. A study was performed with 13 participants to investigate the differences in sensation between the two modes of operation. The results showed that 12 out of 13 participants found the new (distributed-constant-current) approach allowed higher stimulation for the same sensation. The differences in sensation between single and multiple sources became larger with higher intensity levels.

A case of Klinefelter syndrome with hypersexual desire.

Klinefelter syndrome (KS) is a chromosomal disorder affecting males, with the typical karyotype of 47,XXY due to a supernumerary X chromosome, which causes progressive testicular failure resulting in androgen deficiency and infertility. Despite it being the most common sex chromosomal disorder, its diagnosis is easily missed. In addition to its classical clinical features of tall stature, gynaecomastia, small testes, and symptoms and signs of hypogonadism including infertility, KS is also often associated with neurocognitive, behavioural and psychiatric disorders. We present a 44-year-old man with KS who, despite having erectile dysfunction, paradoxically had increased libido. He used sildenafil to overcome his erectile dysfunction. Hypersexuality was manifested by very frequent masturbation, multiple sexual partners most of whom were casual, and a sexual offence conviction at the age of 17 years. Discussion focuses on the frequent failure of clinicians to diagnose KS, the neurocognitive, behavioural and psychiatric aspects of KS, this unusual presentation of hypersexuality in a man with KS, and the challenges of medical management of hypogonadism in a man with a history of a sexual offence. LEARNING POINTS: Klinefelter syndrome (KS) is common in men (about 1 in 600 males), but the diagnosis is very often missed.In addition to classic features of hypogonadism, patients with KS can often have associated neurocognitive, behavioural and/or psychiatric disorders.More awareness of the association between KS and difficulties related to verbal skills in boys could improve rates of early diagnosis and prevent longer-term psychosocial disability.Hypersexuality in the context of hypogonadism raises the possibility of sex steroid independent mechanistic pathways for libido.Testosterone replacement therapy in KS with hypersexuality should be undertaken with caution using a multidisciplinary team approach.

Magnetic induction spectroscopy (MIS)-probe design for cervical tissue measurements.

OBJECTIVE: Gradiometers have the advantage of increasing measuring sensitivity, which is particularly useful in magnetic induction spectroscopy (MIS) for bio-impedance measurements. Traditional gradiometers use a pair of field sensing coils equally distant and on opposite sides of a drive coil, which provides high immunity to interference. In this paper, a ferrite-cored coaxial gradiometer probe of 29 mm diameter has been developed for measuring the impedance spectra of cervical tissues in vivo. APPROACH: It consists of a ferrite rod with outer ferrite confinement screening in order to eliminate the signals from surrounding tissue. The magnetic screening efficiency was compared with an air-cored gradiometer probe. For both gradiometer probes, a drive coil and two sensing coils were wound on a borosilicate glass former aligned coaxially with two sensing coils equidistant from the drive coil. The signal sensitivity of those two MIS gradiometers has been measured using saline samples with a conductivity range between 0.1 and 1.1 S m-1. Finite element methods using COMSOL Multiphysics have been used to simulate the distribution of sensitivity to conductivity over the face of each probe and with depth. MAIN RESULTS: The ferrite-cored probe has a sensitivity confined to the volume defined by the gap between the ferrite core and outer tube of ferrite while the air-cored probe without any magnetic shielding had a wide sensitivity over the face and the side of the probe. Four saline samples and one of distilled water with conductivities from 0.1 to 1.1 S m-1 have been used to make conductivity measurements at frequencies of 50 kHz, 100 kHz, and 300 kHz. The measurement accuracy of the air-cored MIS probe was 0.09 S m-1 at 50 kHz, improving to 0.05 S m-1 at 300 kHz. For the ferrite-cored MIS probe, the measurement accuracy was 0.28 S m-1 at 50 kHz, improving to 0.04 S m-1 at 300 kHz. SIGNIFICANCE: In vivo measurements on human hand have been performed using both types of gradiometers and the conductivity is consistent with reported data.

Evaluation of olanzapine pamoate depot in seriously violent males with schizophrenia in the community.

OBJECTIVES: Olanzapine is a well established treatment for schizophrenia. The olanzapine pamoate depot (long-acting injectable) formulation improves compliance and clinical trials have shown it to be effective. However, there are no previously published reports evaluating olanzapine depot in violent patients with schizophrenia in the community. We evaluated the clinical efficacy of olanzapine depot, its effect on violence, hospitalization and incarceration in community patients with schizophrenia and prior history of serious violence. METHODS: This was a retrospective service evaluation in a community forensic psychiatry service where patients had schizophrenia spectrum disorder and a significant history of violence. Treatment resistance, substance use disorders and antisocial personality disorder were common. Nine deidentified patient records were audited for 12 months pre and 12 months post olanzapine depot initiation to identify any clinical changes, breaches of (legislated) psychiatric treatment orders, hospital admission days, days incarcerated and emergency presentations. RESULTS: Community forensic psychiatric patients treated with olanzapine depot showed an improvement in psychotic symptoms (p = 0.008) with overall decreases in violence, supported by reductions in hospitalization days (p = 0.018) and days incarcerated (p = 0.043). Several patients had reduced psychiatric treatment order breaches and emergency presentations. CONCLUSIONS: Community forensic psychiatric patients with schizophrenia responded to olanzapine depot with decreased violence and reduced hostility. A depot antipsychotic medication that reduces violence and improves engagement has significant implications for greater effective community management of forensic patients with schizophrenia.

A review of the design and clinical evaluation of the ShefStim array-based functional electrical stimulation system.

Functional electrical stimulation has been shown to be a safe and effective means of correcting foot drop of central neurological origin. Current surface-based devices typically consist of a single channel stimulator, a sensor for determining gait phase and a cuff, within which is housed the anode and cathode. The cuff-mounted electrode design reduces the likelihood of large errors in electrode placement, but the user is still fully responsible for selecting the correct stimulation level each time the system is donned. Researchers have investigated different approaches to automating aspects of setup and/or use, including recent promising work based on iterative learning techniques. This paper reports on the design and clinical evaluation of an electrode array-based FES system for the correction of drop foot, ShefStim. The paper reviews the design process from proof of concept lab-based study, through modelling of the array geometry and interface layer to array search algorithm development. Finally, the paper summarises two clinical studies involving patients with drop foot. The results suggest that the ShefStim system with automated setup produces results which are comparable with clinician setup of conventional systems. Further, the final study demonstrated that patients can use the system without clinical supervision. When used unsupervised, setup time was 14min (9min for automated search plus 5min for donning the equipment), although this figure could be reduced significantly with relatively minor changes to the design.

Effect of 900 MHz electromagnetic fields on nonthermal induction of heat-shock proteins in human leukocytes.

Despite many studies, the evidence as to whether radiofrequency fields are detrimental to health remains controversial, and the debate continues. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. The aim of this study was to determine whether exposure to mobile phone-type radiation causes a nonthermal stress response in human leukocytes. Human peripheral blood was sham-exposed or exposed to 900 MHz fields (continuous-wave or GSM-modulated signal) at three average specific absorption rates (0.4, 2.0 and 3.6 W/kg) for different durations (20 min, 1 h and 4 h) in a calibrated TEM cell placed in an incubator to give well-controlled atmospheric conditions at 37 degrees C and 95% air/5% CO(2). Positive (heat-stressed at 42 degrees C) and negative (kept at 37 degrees C) control groups were incubated simultaneously in the same incubator. Heat caused an increase in the number of cells expressing stress proteins (HSP70, HSP27), measured using flow cytometry, and this increase was dependent on time. However, no statistically significant difference was detected in the number of cells expressing stress proteins after RF-field exposure. These results suggest that mobile phone-type radiation is not a stressor of normal human lymphocytes and monocytes, in contrast to mild heating.

Non-invasive transcutaneous electrical stimulation in the treatment of overactive bladder.

We reviewed the literature on transcutaneous electrical nerve stimulation (TENS) used as a therapy for overactive bladder (OAB) symptoms, with a particular focus on: stimulation site, stimuli parameters, neural structures thought to be targeted, and the clinical and urodynamic outcomes achieved. The majority of studies used sacral or tibial nerve stimulation. The literature suggests that, whilst TENS therapy may have neuromodulation effects, patient are unlikely to benefit to a significant extent from a single application of TENS and indeed clear benefits from acute studies have not been reported. In long-term studies there were differences in the descriptions of stimulation intensity, strategy of the therapy, and positioning of the electrodes, as well as in the various symptoms and pathology of the patients. Additionally, most studies were uncontrolled and hence did not evaluate the placebo effect. Little is known about the underlying mechanism by which these therapies work and therefore exactly which structures need to be stimulated, and with what parameters. There is promising evidence for the efficacy of a transcutaneous stimulation approach, but adequate standardisation of stimulation criteria and outcome measures will be necessary to define the best way to administer this therapy and document its efficacy.

Randomized blinded control trial into tourniquet tolerance in awake volunteers.

BACKGROUND: The ability to tolerate a tourniquet is often the limiting factor to elective and emergent procedures of the upper limb performed under local anaesthesia. This study aims to demonstrate that upper limb tourniquets are more predictably and better tolerated when inflated to 200 mmHg than to the traditional inflation pressure of 250 mmHg in awake, unsedated subjects. METHODS: Forty healthy volunteers were randomized to have a tourniquet applied at either 200 or 250 mmHg for 20 min. Vital signs and pain scores were measured pre-test, at intervals throughout the time the tourniquet was inflated and post-deflation until the parameters normalized. Grip strength was measured pre-test, immediately post-deflation of the tourniquet and every 2 min until return of normal strength. RESULTS: All subjects were able to tolerate a tourniquet inflated for the allocated 20 min irrespective of the inflation pressure; however, there was a statistically significant lower average pain score in the group where the tourniquet was inflated to 200 mmHg compared with 250 mmHg. There was a quicker return of normal grip strength, although this was not shown to be statistically significant. CONCLUSIONS: Tourniquets inflated to 200 mmHg are better tolerated in awake, unsedated subjects that would allow predictably short procedures of the hand, wrist and forearm to be performed under local anaesthesia. It represents a pilot study prior to a further clinical study investigating the efficacy of tourniquets inflated to a lower pressure in maintaining an effective bloodless field.

Enhancing public involvement in assistive technology design research.

PURPOSE: To appraise the application of accepted good practice guidance on public involvement in assistive technology research and to identify its impact on the research team, the public, device and trial design. METHODS: Critical reflection and within-project evaluation were undertaken in a case study of the development of a functional electrical stimulation device. Individual and group interviews were undertaken with lay members of a 10 strong study user advisory group and also research team members. RESULTS: Public involvement was seen positively by research team members, who reported a positive impact on device and study designs. The public identified positive impact on confidence, skills, self-esteem, enjoyment, contribution to improving the care of others and opportunities for further involvement in research. A negative impact concerned the challenge of engaging the public in dissemination after the study end. CONCLUSIONS: The public were able to impact significantly on the design of an assistive technology device which was made more fit for purpose. Research team attitudes to public involvement were more positive after having witnessed its potential first hand. Within-project evaluation underpins this case study which presents a much needed detailed account of public involvement in assistive technology design research to add to the existing weak evidence base. IMPLICATIONS FOR REHABILITATION: The evidence base for impact of public involvement in rehabilitation technology design is in need of development. Public involvement in co-design of rehabilitation devices can lead to technologies that are fit for purpose. Rehabilitation researchers need to consider the merits of active public involvement in research.