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1.
Exp Neurol ; 351: 113977, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35016994

RESUMO

There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the 'Picostim DyNeuMo Mk-1' (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient's movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.


Assuntos
Encéfalo , Transtornos dos Movimentos , Algoritmos , Encéfalo/fisiologia , Cronoterapia , Humanos , Reprodutibilidade dos Testes
2.
Mov Disord ; 36(4): 863-873, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33547859

RESUMO

BACKGROUND: High-frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor. OBJECTIVE: We proposed to close the loop of thalamic stimulation by detecting tremor-provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary. METHODS: Eight patients with essential tremor participated in this study. Patient-specific support vector machine classifiers were first trained using data recorded while the patient performed tremor-provoking movements. Then, the trained models were applied in real-time to detect these movements and triggered the delivery of stimulation. RESULTS: Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor-evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor-free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation. CONCLUSIONS: The results suggest that responsive thalamic stimulation for essential tremor based on tremor-provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Tremor Essencial/terapia , Humanos , Movimento , Tálamo , Tremor/terapia
3.
Eur J Neurosci ; 51(2): 628-640, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483893

RESUMO

Understanding the functional dynamics of neural oscillations in the sensory thalamus is essential for elucidating the perception and modulation of neuropathic pain. Local field potentials were recorded from the sensory thalamus of twelve neuropathic pain patients. Single and combinational neural states were defined by the activity state of a single or paired oscillations. Relationships between the duration or occurrence rate of neural state and pre-operative pain level or pain relief induced by deep brain stimulation were evaluated. Results showed that the occurrence rate of the single neural state of low-beta oscillation was significantly correlated with pain relief. The duration and occurrence rate of combinational neural states of the paired low-beta with delta, theta, alpha, high-beta or low-gamma oscillations were more significantly correlated with pain relief than the single neural states. Moreover, these significant combinational neural states formed a local oscillatory network with low-beta oscillation as a key node. The results also showed correlations between measures of combinational neural states and subjective pain level as well. The duration of combinational neural states of paired alpha with delta or theta oscillations and the occurrence rate of neural states of the paired delta with low-beta or low-gamma oscillations were significantly correlated with pre-operative pain level. In conclusion, this study revealed that the integration of oscillations and the functional dynamics of neural states were differentially involved in modulation and perception of neuropathic pain. The functional dynamics could be biomarkers for developing neural state-dependent deep brain stimulation for neuropathic pain.


Assuntos
Neuralgia , Tálamo , Humanos , Neuralgia/terapia
4.
J Clin Neurosci ; 68: 342-343, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31331745

RESUMO

The periaqueductal grey area and sensory thalamus are thought to be important nuclei involved in the supraspinal bladder control network. Deep brain stimulation of the periqueductal grey area has been shown to increase bladder capacity in the human. In a single patient, we have recorded local field potential signals from implanted deep brain stimulation electrodes within the sensory thalamus during filling cystometry with periaqueductal grey area deep brain stimulation in the ON and OFF states. In the OFF stimulation state, we demonstrate correlations between bladder volume and oscillations in the high gamma frequency band in the sensory thalamus. Stimulation of the periaqueductal grey area abolishes this correlated activity in the gamma frequency band and also suppresses oscillations within the sensory thalamus in the alpha frequency band. These findings support the involvement of the sensory thalamus in the afferent limb of bladder-related brain networks. They also suggest that periaqueductal grey area deep brain stimulation may disrupt the normal processing of afferent signals within the sensory thalamus which may be related to the effect of stimulation on bladder capacity.


Assuntos
Estimulação Encefálica Profunda , Substância Cinzenta Periaquedutal/fisiologia , Tálamo/fisiologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Membro Fantasma/terapia
5.
Neuromodulation ; 22(5): 638-644, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31199547

RESUMO

BACKGROUND: Occipital nerve stimulation (ONS) is widely used for headache syndromes including chronic migraine (CM) and chronic cluster headache (CCH). The paraesthesia associated with tonic stimulation can be bothersome and can limit therapy. It is now clear in spinal cord stimulation that paraesthesia-free waveforms can produce effective analgesia, but this has not been reported in ONS for CM or CCH. MATERIALS AND METHODS: Seventeen patients (12 CM and 5 CCH) were treated with bilateral burst pattern ONS, including 4 who had previously had tonic ONS. Results were assessed in terms of the frequency of headaches (number of headache days per month for CM, and number of attacks per day for CCH) and their intensity on the numeric pain rating scale. RESULTS: Burst ONS produced a statistically significant mean reduction of 10.2 headache days per month in CM. In CCH, there were significant mean reductions in headache frequency (92%) and intensity (42%). CONCLUSION: Paraesthesia is not necessary for good quality analgesia in ONS. Larger studies will be required to determine whether the efficacies of the two stimulation modes differ. Burst ONS is imperceptible and therefore potentially amenable to robustly blinded clinical trials.


Assuntos
Cefaleia Histamínica/terapia , Terapia por Estimulação Elétrica/métodos , Transtornos de Enxaqueca/terapia , Manejo da Dor/métodos , Nervos Periféricos/fisiologia , Adulto , Idoso , Doença Crônica , Cefaleia Histamínica/diagnóstico , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Manejo da Dor/instrumentação , Estudos Retrospectivos
6.
Neuromodulation ; 22(5): 645-652, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30629320

RESUMO

BACKGROUND: Trigeminal Neuropathic Pain (TNP) is a chronic facial pain syndrome caused by a lesion or disease affecting one or more branches of the trigeminal nerve. It may, for example, result from accidental injury to a branch of the trigeminal nerve by trauma or during surgery; it may also be idiopathic. TNP is typically constant, in contrast to most cases of the commoner trigeminal neuralgia. In some cases, pain may be refractory to pharmacological treatment. Peripheral nerve field stimulation is recognized as an effective minimally invasive surgical treatment option for this debilitating condition. To date, stimulation has used conventional tonic waveforms, which generate paraesthesia in the stimulated area. This is the first report of the use of paraesthesia-free burst pattern stimulation for TNP. METHODS: Seven patients were treated at the John Radcliffe Hospital for TNP from 2016 to 2018. Mean duration of preoperative symptoms was five years. All patients had exhausted pharmacological measures to limited effect. The initial three patients had tonic stimulation with the subsequent four having burst stimulation. Outcome was assessed using the numeric pain rating scale preoperatively and postoperatively at three and six months and one year. Side-effects and complications were also assessed as well as reduction in analgesic medication use. RESULTS: All patients achieved pain reduction of at least 50% at 6 months (range 50-100%, mean 81%, p = 0.0082). Those in the burst stimulation group were paraesthesia free. One patient developed a postoperative infection for which the system had to be removed and is awaiting reimplantation. There were no other complications in either group. CONCLUSION: Burst stimulation conferred similar pain control to tonic stimulation in our small cohort, and there were similar reductions in pain medication use. An additional benefit of burst stimulation is freedom from paraesthesia. Larger scale studies are needed to further evaluate burst stimulation and compare its efficacy with that of tonic stimulation.


Assuntos
Terapia por Estimulação Elétrica/métodos , Neuralgia Facial/terapia , Manejo da Dor/métodos , Nervos Periféricos/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Neuralgia do Trigêmeo/terapia , Adulto , Idoso , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Neuralgia Facial/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/instrumentação , Estimulação Elétrica Nervosa Transcutânea/instrumentação , Resultado do Tratamento , Neuralgia do Trigêmeo/diagnóstico por imagem
7.
J Neurosci ; 38(22): 5111-5121, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29760182

RESUMO

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20-30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENT Gait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20-30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.


Assuntos
Ritmo beta , Núcleo Subtalâmico/fisiopatologia , Caminhada , Estimulação Acústica , Idoso , Fenômenos Biomecânicos , Sinais (Psicologia) , Estimulação Encefálica Profunda , Eletrodos Implantados , Retroalimentação Psicológica , Feminino , Marcha/fisiologia , Calcanhar/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor
8.
Neurobiol Dis ; 109(Pt A): 117-126, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29031639

RESUMO

OBJECTIVE: Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. APPROACH: Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. MAIN RESULTS: This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. SIGNIFICANCE: The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.


Assuntos
Ondas Encefálicas , Estimulação Encefálica Profunda , Neuralgia/diagnóstico , Neuralgia/fisiopatologia , Tálamo/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/prevenção & controle , Medição da Dor , Substância Cinzenta Periaquedutal/fisiopatologia , Substância Cinzenta Periaquedutal/cirurgia , Análise de Componente Principal , Análise de Regressão , Índice de Gravidade de Doença , Tálamo/cirurgia
9.
Neuromodulation ; 20(5): 504-513, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28631870

RESUMO

OBJECT: Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain. METHODS: Sixteen consecutive patients received 36 months post-surgical follow-up in a single-center. Six had phantom limb pain after amputation and ten deafferentation pain after brachial plexus injury, all due to traumas. To evaluate the efficacy of DBS, patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, University of Washington Neuropathic Pain Score (UWNPS), Brief Pain Inventory (BPI), and 36-Item Short-Form Health Survey (SF-36). RESULTS: Contralateral, ventroposterolateral sensory thalamic DBS was performed in sixteen patients with chronic neuropathic pain over 29 months. A postoperative trial of externalized DBS failed in one patient with brachial plexus injury. Fifteen patients proceeded to implantation but one patient with phantom limb pain after amputation was lost for follow-up after 12 months. No surgical complications or stimulation side effects were noted. After 36 months, mean pain relief was sustained, and the median (and interquartile range) of the improvement of VAS score was 52.8% (45.4%) (p = 0.00021), UWNPS was 30.7% (49.2%) (p = 0.0590), BPI was 55.0% (32.0%) (p = 0.00737), and SF-36 was 16.3% (30.3%) (p = 0.4754). CONCLUSIONS: DBS demonstrated efficacy at three years for chronic neuropathic pain after traumatic amputation and brachial plexus injury, with benefits sustained across all pain outcomes measures and slightly greater improvement in phantom limb pain.


Assuntos
Estimulação Encefálica Profunda/métodos , Estimulação Encefálica Profunda/tendências , Neuralgia/cirurgia , Tálamo/cirurgia , Adulto , Dor Crônica/diagnóstico , Dor Crônica/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Medição da Dor/métodos , Medição da Dor/tendências , Tálamo/fisiologia , Fatores de Tempo
10.
Clin Neurophysiol ; 127(7): 2573-80, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27291876

RESUMO

OBJECTIVE: To investigate the link between neuronal activity recorded from the sensory thalamus and periventricular gray/periaqueductal gray (PVAG) and pain relief by deep brain stimulation (DBS). METHODS: Local field potentials (LFPs) were recorded from the sensory thalamus and PVAG post-operatively from ten patients with neuropathic pain. The LFPs were quantified using spectral and time-frequency analysis, the relationship between the LFPs and pain relief was quantified with nonlinear correlation analysis. RESULTS: The theta oscillations of both sensory thalamus and PVAG correlated inversely with pain relief. The high beta oscillations in the sensory thalamus and the alpha oscillations in the PVAG correlated positively with pain relief. Moreover, the ratio of high-power duration to low-power duration of theta band activity in the sensory thalamus and PVAG correlated inversely with pain relief. The duration ratio at the high beta band in the sensory thalamus correlated positively with pain relief. CONCLUSIONS: Our results reveal distinct neuronal oscillations at the theta, alpha, and beta frequencies correlating with pain relief by DBS. SIGNIFICANCE: The study provides quantitative measures for predicting the outcomes of neuropathic pain relief by DBS as well as potential biomarkers for developing adaptive stimulation strategies.


Assuntos
Estimulação Encefálica Profunda , Potenciais Evocados , Neuralgia/terapia , Adulto , Ondas Encefálicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/fisiopatologia , Tálamo/fisiologia
11.
J Neurosci Methods ; 264: 25-32, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26928256

RESUMO

BACKGROUND: Multiple oscillations emerging from the same neuronal substrate serve to construct a local oscillatory network. The network usually exhibits complex behaviors of rhythmic, balancing and coupling between the oscillations, and the quantification of these behaviors would provide valuable insight into organization of the local network related to brain states. NEW METHOD: An integrated approach to quantify rhythmic, balancing and coupling neural behaviors based upon power spectral analysis, power ratio analysis and cross-frequency power coupling analysis was presented. Deep brain local field potentials (LFPs) were recorded from the thalamus of patients with neuropathic pain and dystonic tremor. t-Test was applied to assess the difference between the two patient groups. RESULTS: The rhythmic behavior measured by power spectral analysis showed significant power spectrum difference in the high beta band between the two patient groups. The balancing behavior measured by power ratio analysis showed significant power ratio differences at high beta band to 8-20 Hz, and 30-40 Hz to high beta band between the patient groups. The coupling behavior measured by cross-frequency power coupling analysis showed power coupling differences at (theta band, high beta band) and (45-55 Hz, 70-80 Hz) between the patient groups. COMPARISON WITH EXISTING METHOD: The study provides a strategy for studying the brain states in a multi-dimensional behavior space and a framework to screen quantitative characteristics for biomarkers related to diseases or nuclei. CONCLUSIONS: The work provides a comprehensive approach for understanding the complex behaviors of deep brain LFPs and identifying quantitative biomarkers for brain states related to diseases or nuclei.


Assuntos
Ondas Encefálicas/fisiologia , Estimulação Encefálica Profunda/métodos , Distonia/fisiopatologia , Rede Nervosa/fisiologia , Neuralgia/fisiopatologia , Tálamo/fisiologia , Tremor/fisiopatologia , Adulto , Humanos , Pessoa de Meia-Idade
12.
World Neurosurg ; 86: 361-70.e1-3, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26344354

RESUMO

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.


Assuntos
Dor Crônica/cirurgia , Estimulação Encefálica Profunda/métodos , Imagem de Tensor de Difusão/métodos , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/cirurgia , Procedimentos Neurocirúrgicos/métodos , Eletrodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Feixe Prosencefálico Mediano/anatomia & histologia , Feixe Prosencefálico Mediano/cirurgia , Pessoa de Meia-Idade , Medição da Dor , Tálamo/anatomia & histologia , Tálamo/cirurgia , Resultado do Tratamento
13.
J Clin Neurosci ; 22(10): 1537-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26122383

RESUMO

Deep brain stimulation (DBS) is a neurosurgical intervention popularised in movement disorders such as Parkinson's disease, and also reported to improve symptoms of epilepsy, Tourette's syndrome, obsessive compulsive disorders and cluster headache. Since the 1950s, DBS has been used as a treatment to relieve intractable pain of several aetiologies including post stroke pain, phantom limb pain, facial pain and brachial plexus avulsion. Several patient series have shown benefits in stimulating various brain areas, including the sensory thalamus (ventral posterior lateral and medial), the periaqueductal and periventricular grey, or, more recently, the anterior cingulate cortex. However, this technique remains "off label" in the USA as it does not have Federal Drug Administration approval. Consequently, only a small number of surgeons report DBS for pain using current technology and techniques and few regions approve it. Randomised, blinded and controlled clinical trials that may use novel trial methodologies are desirable to evaluate the efficacy of DBS in patients who are refractory to other therapies. New imaging techniques, including tractography, may help optimise electrode placement and clinical outcome.


Assuntos
Analgesia/métodos , Dor Crônica/terapia , Estimulação Encefálica Profunda , Dor Intratável/terapia , Adulto , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Eletrodos Implantados , Giro do Cíngulo , Humanos , Procedimentos Neurocirúrgicos , Substância Cinzenta Periaquedutal , Tálamo , Resultado do Tratamento
14.
Br J Neurosurg ; 29(3): 334-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25757503

RESUMO

INTRODUCTION: Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. MATERIALS AND METHODS: Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. RESULTS: I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0.0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0.001), 20% had 11 correct perceptions (p = 0.013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. CONCLUSIONS: DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. CLASSIFICATION OF EVIDENCE: This study is the first to provide Class I evidence for the efficacy of DBS for ET.


Assuntos
Estimulação Encefálica Profunda , Eletrodos Implantados , Tremor Essencial/terapia , Idoso , Estimulação Encefálica Profunda/métodos , Tremor Essencial/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Núcleo Subtalâmico/fisiopatologia , Tálamo/fisiopatologia , Resultado do Tratamento
15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 3779-82, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26737116

RESUMO

A functioning thalamus is essential for treatment of patients with disorders of consciousness (DOC) using deep brain stimulation (DBS). This work aims to identify the potential biomarkers related to consciousness from the thalamic deep brain local field potentials (LFPs) in DOC patients. The frequency features of central thalamic LFPs were characterized with spectral analysis. The features were further compared to those of LFPs from the ventroposterior lateral nucleus of the thalamus (VPL) in patients with pain. There are several distinct characteristics of thalamic LFPs found in patients with DOC. The most important feature is the oscillation around 10Hz which could be relevant to the existence of residual consciousness, whereas high power below 8Hz seemed to be associated with loss of consciousness. The invasive deep brain recording tool opens a unique way to explore the brain function in consciousness, awareness and alertness and clarify the potential mechanisms of thalamic stimulation in DOC.


Assuntos
Tálamo/fisiopatologia , Potenciais de Ação , Adulto , Conscientização , Encéfalo/fisiopatologia , Estado de Consciência , Transtornos da Consciência/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Neurotherapeutics ; 11(3): 496-507, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24867325

RESUMO

Deep brain stimulation (DBS) is a neurosurgical intervention the efficacy, safety, and utility of which are established in the treatment of Parkinson's disease. For the treatment of chronic, neuropathic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated with current standards of neuroimaging and stimulator technology over the last decade . We summarize the history, science, selection, assessment, surgery, programming, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and latterly rostral anterior cingulate cortex (Cg24) in 113 patients treated at 2 centers (John Radcliffe, Oxford, UK, and Hospital de São João, Porto, Portugal) over 13 years. Several experienced centers continue DBS for chronic pain, with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS under general anesthesia considered for whole or hemibody pain, or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.


Assuntos
Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/métodos , Neuralgia/terapia , Estimulação Encefálica Profunda/história , História do Século XX , Humanos , Seleção de Pacientes , Substância Cinzenta Periaquedutal/fisiopatologia , Tálamo/fisiopatologia
17.
Soc Cogn Affect Neurosci ; 9(7): 977-84, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23720574

RESUMO

Infant vocalizations are among the most biologically salient sounds in the environment and can draw the listener to the infant rapidly in both times of distress and joy. A region of the midbrain, the periaqueductal gray (PAG), has long been implicated in the control of urgent, survival-related behaviours. To test for PAG involvement in the processing of infant vocalizations, we recorded local field potentials from macroelectrodes implanted in this region in four adults who had undergone deep brain stimulation. We found a significant difference occurring as early as 49 ms after hearing a sound in activity recorded from the PAG in response to infant vocalizations compared with constructed control sounds and adult and animal affective vocalizations. This difference was not present in recordings from thalamic electrodes implanted in three of the patients. Time frequency analyses revealed distinct patterns of activity in the PAG for infant vocalisations, constructed control sounds and adult and animal vocalisations. These results suggest that human infant vocalizations can be discriminated from other emotional or acoustically similar sounds early in the auditory pathway. We propose that this specific, rapid activity in response to infant vocalizations may reflect the initiation of a state of heightened alertness necessary to instigate protective caregiving.


Assuntos
Percepção Auditiva/fisiologia , Linguagem Infantil , Choro , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Acústica , Adulto , Animais , Dor Crônica/fisiopatologia , Dor Crônica/terapia , Estimulação Encefálica Profunda , Discriminação Psicológica/fisiologia , Feminino , Humanos , Neuroestimuladores Implantáveis , Lactente , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tálamo/fisiologia , Fatores de Tempo , Comportamento Verbal , Vocalização Animal
18.
Exp Brain Res ; 232(2): 527-34, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24217977

RESUMO

Pain perception can be altered by activity in the periaqueductal gray (PAG). The PAG can decrease the incoming nociceptive signals at the level of the spinal dorsal horn, but it is not clear whether the PAG can also affect the sensory thalamus, ventral posterolateral and ventral posteromedial thalamic nuclei, to modulate pain. However, the PAG and the thalamus have direct connections with each other; so we postulated that the PAG may also modulate pain by inhibiting the sensory nuclei in the thalamus, and that these may also reciprocally influence the PAG. Here, by analyzing the local field potentials recorded from the sensory thalamus and the PAG in chronic pain patients with deep brain stimulation electrodes, we show that PAG stimulation inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus stimulation excited the PAG with increasing PAG delta and theta power. We demonstrate that the PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation.


Assuntos
Neuralgia/fisiopatologia , Percepção da Dor/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Tálamo/fisiologia , Adulto , Estimulação Encefálica Profunda/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Neuralgia/terapia , Medição da Dor , Análise Espectral
19.
Curr Biol ; 23(5): 436-40, 2013 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-23416101

RESUMO

Tremor can dominate Parkinson's disease and yet responds less well to dopaminergic medications than do other cardinal symptoms of this condition. Deep brain stimulation can provide striking tremor relief, but the introduction of stimulating electrodes deep in the substance of the brain carries significant risks, including those of hemorrhage. Here, we pioneer an alternative approach in which we noninvasively apply transcranial alternating current stimulation (TACS) over the motor cortex to induce phase cancellation of the rest tremor rhythm. We first identify the timing of cortical oscillations responsible for rest tremor in the periphery by delivering tremor-frequency stimulation over motor cortex but do not couple this stimulation to the on-going tremor-instead, the rhythms simply "drift" in and out of phase alignment with one another. Slow alternating periods of phase cancellation and reinforcement result, informing on the phase alignments that induce the greatest change in tremor amplitude. Next, we deliver stimulation at these specified phase alignments to demonstrate controlled suppression of the on-going tremor. With this technique we can achieve almost 50% average reduction in resting tremor amplitude and in so doing form the basis of a closed-loop tremor-suppression therapy that could be extended to other oscillopathies.


Assuntos
Terapia por Estimulação Elétrica , Córtex Motor , Tremor/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Tremor/etiologia
20.
Neuromodulation ; 16(2): 121-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22257117

RESUMO

OBJECTIVES: To assess the effect of peripheral nerve stimulation on neuropathic testicular pain. MATERIAL AND METHODS: A 30-year-old man with a four-year history of chronic testicular pain following scrotal hydrocele surgery had two percutaneous leads implanted in his groin and low-frequency stimulation of the cutaneous branch of the ilioinguinal and genital branch of the genitofemoral nerves. RESULT: At seven-month follow-up, the pain intensity had declined from 9/10 to 2/10 on the numeric rating scale. CONCLUSION: We report the successful implantation of an ilioinguinal and genitofemoral nerve stimulator for sustained suppression of intractable neuropathic testicular pain.


Assuntos
Dor Pós-Operatória/terapia , Nervos Periféricos/fisiologia , Doenças Testiculares/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Adulto , Dor Crônica , Seguimentos , Virilha/inervação , Humanos , Canal Inguinal/inervação , Masculino , Dor Pós-Operatória/complicações , Doenças Testiculares/complicações
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