RESUMEN
OBJECTIVE: Deep brain stimulation (DBS) is an effective surgical treatment for patients with Parkinson's disease (PD). DBS therapy, particularly with the subthalamic nucleus (STN) target, has been linked to rare psychiatric complications, including depression, impulsivity, irritability, and suicidality. Stimulation-induced elevated mood states can also occur. These episodes rarely meet DSM-5 criteria for mania or hypomania. METHODS: The investigators conducted a chart review of 82 patients with PD treated with DBS. RESULTS: Nine (11%) patients developed stimulation-induced elevated mood. Five illustrative cases are described (all males with STN DBS; mean age=62.2 years [SD=10.5], mean PD duration=8.6 years [SD=1.6]). Elevated mood states occurred during or shortly after programming changes, when more ventral contacts were used (typically in monopolar mode) and lasted minutes to months. Four patients experienced elevated mood at low amplitudes (1.0 V/1.0 mA); all had psychiatric risk factors (history of impulse-control disorder, dopamine dysregulation syndrome, substance use disorder, and/or bipolar diathesis) that likely contributed to mood destabilization. CONCLUSIONS: Preoperative DBS evaluations should include a thorough assessment of psychiatric risk factors. The term "stimulation-induced elevated mood states" is proposed to describe episodes of elevated, expansive, or irritable mood and psychomotor agitation that occur during or shortly after DBS programming changes and may be associated with increased goal-directed activity, impulsivity, grandiosity, pressured speech, flight of ideas, or decreased need for sleep and may persist beyond stimulation adjustments. This clinical phenomenon should be considered for inclusion in the bipolar disorder category in future DSM revisions, allowing for increased recognition and appropriate management.
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Trastorno Bipolar/diagnóstico , Estimulación Encefálica Profunda/efectos adversos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/diagnóstico , Trastornos del Humor/diagnóstico , Enfermedad de Parkinson/complicaciones , Anciano , Trastorno Bipolar/etiología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/etiología , Humanos , Conducta Impulsiva , Masculino , Manía , Persona de Mediana Edad , Trastornos del Humor/etiología , Núcleo Subtalámico , Resultado del TratamientoRESUMEN
Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
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Encéfalo/fisiopatología , Estimulación Encefálica Profunda/métodos , Red Nerviosa/fisiopatología , Síndrome de Tourette/terapia , Adulto , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Estudios Retrospectivos , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: In Parkinson's disease (PD) patients, the subthalamic nucleus (STN) has prominent oscillatory activity in the beta band, which may be related to the motor symptoms severity. Local field potential (LFP) studies using standard four-contact deep brain stimulation (DBS) leads indicate that the source of beta activity in the STN region is the dorsolateral segment of the nucleus. However, these leads have few contacts outside of the STN, making the source localization of beta activity around the STN region uncertain. OBJECTIVE: This study aimed to investigate the electrophysiological characteristics of the STN and the surrounding area in PD to better locate the source of these oscillations and their clinical relevance. METHODS: Eight PD patients were bilaterally implanted in the STN with the eight ring-contact DBS lead (Boston Scientific Corporation). LFPs were recorded intra-operatively from each DBS contact in the off medication state at rest. Each contact location was normalized relative to the STN borders based on microelectrode recordings. For each recording, power spectral density was computed, averaged over multiple frequency bands and phase reversal analysis was used to localize the source of oscillatory activity. Beta burst, high-frequency activity (HFA), and phase-amplitude coupling (PAC) were also computed. Neurophysiological signatures were correlated with hemibody symptoms severity and clinical outcomes. RESULTS: Beta band power and phase reversal localized the beta oscillator to the dorsal STN and correlated with pre-operative off medication hemibody bradykinesia and rigidity score. The contact along the electrode with the largest beta oscillatory power co-localized with the independently chosen optimized contact used for long-term chronic DBS. Lastly, beta bursting, HFA, and Beta-HFA PAC co-localized with the beta oscillator at the dorsal STN, and Beta-HFA PAC correlated with DBS effect. CONCLUSIONS: Our findings support the hypothesis that the primary source of beta oscillations is located in dorsal STN, and argue against the alternative hypothesis that beta activity in the STN region arises from volume conduction from other sources. We demonstrate intrinsic STN beta-HFA PAC as an independent marker of DBS effect.
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Estimulación Encefálica Profunda , Red Nerviosa/fisiopatología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/cirugía , Anciano , Encéfalo/fisiopatología , Encéfalo/cirugía , Fenómenos Electrofisiológicos/fisiología , Femenino , Humanos , Masculino , Microelectrodos , Persona de Mediana Edad , Red Nerviosa/cirugía , Núcleo Subtalámico/fisiopatologíaRESUMEN
A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.
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Corteza Cerebral/fisiología , Estimulación Encefálica Profunda/métodos , Potenciales Evocados/fisiología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiología , Corteza Cerebral/diagnóstico por imagen , Electrocorticografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Distribución Aleatoria , Núcleo Subtalámico/diagnóstico por imagenRESUMEN
In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13-20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4-8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression.
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Ritmo beta , Estimulación Encefálica Profunda/métodos , Globo Pálido , Corteza Motora/fisiopatología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Adulto , Anciano , Ganglios Basales/fisiopatología , Distonía/fisiopatología , Distonía/terapia , Electrocorticografía , Electrodos Implantados , Sincronización de Fase en Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ritmo Teta , Adulto JovenRESUMEN
The objective of this study was to evaluate proposed electroencephalographic (EEG) biomarkers of Parkinson's disease (PD) and test their correlation with motor impairment in a new, well-characterized cohort of PD patients and controls. Sixty-four-channel EEG was recorded from 14 patients with rigid-akinetic PD with minimal tremor and from 14 age-matched healthy controls at rest and during voluntary movement. Patients were tested off and on medication during a single session. Recordings were analyzed for phase-amplitude coupling over sensorimotor cortex and for pairwise coherence from all electrode pairs in the recording montage (distributed coherence). Phase-amplitude coupling and distributed coherence were found to be elevated Off compared with On levodopa, and their reduction was correlated with motor improvement. In the Off medication state, phase-amplitude coupling was greater in sensorimotor contacts contralateral to the most affected body part and reduced by voluntary movement. We conclude that phase-amplitude coupling and distributed coherence are cortical biomarkers of the parkinsonian state that are detectable noninvasively and may be useful as objective aids for management of dopaminergic therapy. Several analytic methods may be used for noninvasive measurement of abnormal brain synchronization in PD. Calculation of phase-amplitude coupling requires only a single electrode over motor cortex. NEW & NOTEWORTHY Several EEG biomarkers of the parkinsonian state have been proposed that are related to abnormal cortical synchronization. We report several new findings in this study: correlations of EEG markers of synchronization with specific motor signs of Parkinson's disease (PD), and demonstration that one of the EEG markers, phase-amplitude coupling, is more elevated over the more clinically affected brain hemisphere. These findings underscore the potential utility of scalp EEG for objective, noninvasive monitoring of medication state in PD.
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Antiparkinsonianos/farmacología , Electroencefalografía/efectos de los fármacos , Levodopa/farmacología , Enfermedad de Parkinson/fisiopatología , Anciano , Antiparkinsonianos/uso terapéutico , Electroencefalografía/normas , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.
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Estimulación Encefálica Profunda/métodos , Globo Pálido/diagnóstico por imagen , Cápsula Interna/diagnóstico por imagen , Núcleo Accumbens/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Síndrome de Tourette/terapia , Adolescente , Adulto , Atlas como Asunto , Estudios de Cohortes , Conducta Compulsiva/psicología , Femenino , Humanos , Núcleos Talámicos Intralaminares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Conducta Obsesiva/psicología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/psicología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: In Parkinson's disease, the emergence of motor dysfunction is thought to be related to an imbalance between "antikinetic" and "prokinetic" patterns of oscillatory activity in the motor network. Invasive recordings from the basal ganglia and cortex in surgical patients have suggested that levodopa and therapeutic deep brain stimulation can suppress antikinetic beta band (13-30 Hz) rhythms while promoting prokinetic gamma band (60-90 Hz) rhythms. Surgical ablation of the globus pallidus internus is one of the oldest effective therapies for Parkinson's disease and produces remarkably immediate relief of rigidity and bradykinesia, but its effects on oscillatory activity in the motor network have not been studied. OBJECTIVES: We characterize the effects of pallidotomy on cortical oscillatory activity in Parkinson's patients. METHODS: Using a temporary 6-contact lead placed over the sensorimotor cortex in the subdural space, we recorded acute changes in cortical oscillatory activities in 3 Parkinson's disease patients undergoing pallidotomy and compared the results to that of 3 essential tremor patients undergoing thalamotomy. RESULTS: In all 3 Parkinson's disease patients, we observed the emergence of a ~70-80 Hz narrowband oscillation with effective thermolesion of the pallidum. This gamma oscillatory activity was spatially localized over the primary motor cortex, was minimally affected by voluntary movements, and was not found in the motor cortex of essential tremor patients undergoing thalamotomy. CONCLUSIONS: Our finding suggests that acute lesioning of the pallidum promotes cortical gamma band oscillations. This may represent an important mechanism for alleviating bradykinesia in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.
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Ritmo Gamma/fisiología , Globo Pálido/fisiopatología , Corteza Motora/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Globo Pálido/cirugía , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Enfermedad de Parkinson/cirugíaRESUMEN
OBJECTIVE: Parkinson's disease (PD) is a quintessential neuropsychiatric condition in which anxiety and depressive symptoms are common and may precede motor manifestations. The authors explored the ages at onset of anxiety and depressive disorders among patients with PD evaluated by psychiatrists at a deep brain stimulation center. METHODS: Psychiatric diagnoses and ages at onset were collected via clinical interviews. The ages at PD diagnosis were ascertained by chart review. Onset ages for anxiety and depressive disorders (overall and for specific disorders) were compared with patients' ages at PD diagnosis by using t tests. Onset ages for major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder were compared with typical onset ages in the general population by using the sign test. A total of 108 patients (66.7% men; age 63.7 years [SD=8.9]) were included in the analysis. RESULTS: Anxiety and depressive disorders occurred significantly earlier than PD diagnoses. Among patients whose anxiety and depression predated motor symptoms, the mean age at onset of anxiety disorders was 25.6 years earlier, and the mean age at onset of depressive disorders was 17.6 years earlier compared with the mean age at PD diagnosis (both p values <0.0001). Median onset ages for MDD (p<0.0001), GAD (p=0.0002), and panic disorder (p=0.0005) were significantly higher than typical median onset ages in the general population. CONCLUSIONS: These results may indicate that neurodegenerative changes are present in parts of the brainstem reticular core and limbic system before motor circuits are affected to a degree that causes motor symptoms. Psychiatrists should be mindful that onset of MDD, GAD, and panic disorder after age 45 might signal a neurodegenerative movement disorder such as PD.
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Edad de Inicio , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/epidemiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Nonrechargeable deep brain stimulation implantable pulse generators (IPGs) for movement disorders require surgical replacement every few years due to battery depletion. Rechargeable IPGs reduce frequency of replacement surgeries and inherent risks of complications but require frequent recharging. Here, we evaluate patient experience with rechargeable IPGs and define predictive characteristics for higher satisfaction. METHODS: We contacted all patients implanted with rechargeable IPGs at a single center in a survey-based study. We analyzed patient satisfaction with respect to age, diagnosis, target, charging duration, and body mass index. We tabulated hardware-related adverse events. RESULTS: Dystonia patients had significantly higher satisfaction than Parkinson's disease patients in recharging, display, programmer, and training domains. Common positive responses were "fewer surgeries" and "small size." Common negative responses were "difficulty finding the right position to recharge" and "need to recharge every day." Hardware-related adverse events occurred in 21 of 59 participants. CONCLUSION: Patient experience with rechargeable IPGs was largely positive; however, frustrations with recharging and adverse events were common. Dystonia diagnosis was most predictive of high satisfaction across multiple categories, potentially related to expected long disease duration with need for numerous IPG replacements.
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Estimulación Encefálica Profunda/psicología , Suministros de Energía Eléctrica , Electrodos Implantados/psicología , Neuroestimuladores Implantables/psicología , Trastornos del Movimiento/psicología , Trastornos del Movimiento/terapia , Adulto , Anciano , Estimulación Encefálica Profunda/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the safety and effectiveness of a wrist-worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in-office session. METHODS: This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40-minute stimulation session. The primary endpoint compared spiral drawing in the stimulated hand using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes spiral scores in treatment and sham groups. Additional endpoints included TETRAS upper limb tremor scores, subject-rated tasks from the Bain and Findley activities of daily living (ADL) scale before and after stimulation as well as clinical global impression-improvement (CGI-I) rating after stimulation. RESULTS: Subjects who received peripheral nerve stimulation did not show significantly larger improvement in the Archimedes spiral task compared to sham but did show significantly greater improvement in upper limb TETRAS tremor scores (p = 0.017) compared to sham. Subject-rated improvements in ADLs were significantly greater with treatment (49% reduction) than with sham (27% reduction; p = 0.001). A greater percentage of ET patients (88%) reported improvement in the stimulation group as compared to the sham group (62%) according to CGI-I ratings (p = 0.019). No significant adverse events were reported; 3% of subjects experienced mild adverse events. CONCLUSIONS: Peripheral nerve stimulation in ET may provide a safe, well-tolerated, and effective treatment for transient relief of hand tremor symptoms.
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Actividades Cotidianas , Temblor Esencial/diagnóstico , Temblor Esencial/terapia , Nervios Periféricos/fisiología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Actividades Cotidianas/psicología , Anciano , Anciano de 80 o más Años , Temblor Esencial/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Eléctrica Transcutánea del Nervio/instrumentación , Muñeca/inervación , Muñeca/fisiologíaRESUMEN
BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) surgery is clinically effective for treatment of cervical dystonia; however, the underlying physiology has not been examined. We used transcranial magnetic stimulation (TMS) to examine the effects of STN DBS on sensorimotor integration, sensorimotor plasticity and motor cortex excitability, which are identified as the key pathophysiological features underlying dystonia. METHODS: TMS paradigms of short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) were used to examine the sensorimotor integration. Sensorimotor plasticity was measured with paired associative stimulation paradigm, and motor cortex excitability was examined with short interval intracortical inhibition and intracortical facilitation. DBS was turned off and on to record these measures. RESULTS: STN DBS modulated SAI and LAI, which correlated well with the acute clinical improvement. While there were no changes seen in the motor cortex excitability, DBS was found to normalise the sensorimotor plasticity; however, there was no clinical correlation. CONCLUSION: Modulation of sensorimotor integration is a key contributor to clinical improvement with acute stimulation of STN. Since the motor cortex excitability did not change and the change in sensorimotor plasticity did not correlate with clinical improvement, STN DBS demonstrates restricted effects on the underlying physiology. CLINICAL TRIAL REGISTRATION: NCT01671527.
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Estimulación Encefálica Profunda , Corteza Motora/fisiopatología , Núcleo Subtalámico/fisiología , Tortícolis/fisiopatología , Estimulación Magnética Transcraneal , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.
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Estimulación Encefálica Profunda/métodos , Enfermedad de Parkinson/terapia , Núcleo Tegmental Pedunculopontino/fisiología , Humanos , PubMed/estadística & datos numéricosRESUMEN
BACKGROUND: X-linked dystonia parkinsonism (XDP) causes adult-onset progressive dystonia and parkinsonism, which may not respond to pharmacotherapy. OBJECTIVE: Previous case reports have reported beneficial effects from bilateral pallidal (GPi) deep brain stimulation (DBS). Here, we report the long-term clinical outcomes of 3 patients treated at our center. METHODS: All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Adverse events were recorded. RESULTS: The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other. CONCLUSION: Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms.
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Estimulación Encefálica Profunda/tendencias , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Globo Pálido/fisiología , Adulto , Estimulación Encefálica Profunda/métodos , Trastornos Distónicos/complicaciones , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/terapia , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS. SIGNIFICANCE STATEMENT: Oscillations in brain networks link functionally related brain areas to accomplish thought and action, but this mechanism may be altered or exaggerated by disease states. Invasive recording using implanted electrodes provides a degree of spatial and temporal resolution that is ideal for analysis of network oscillations. Here we used a novel, totally implanted, bidirectional neural interface for chronic multisite brain recordings in humans with Parkinson's disease. We characterized an oscillation between cortex and subcortical modulators that is associated with a serious adverse effect of therapy for Parkinson's disease: dyskinesia. The work shows how a perturbation in oscillatory dynamics might lead to a state of excessive movement and also suggests a possible biomarker for feedback-controlled neurostimulation to treat hyperkinetic disorders.
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Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastorno por Déficit de Atención con Hiperactividad/patología , Encéfalo/fisiopatología , Ritmo Gamma/fisiología , Enfermedad de Parkinson/complicaciones , Estimulación Encefálica Profunda , Electroencefalografía , Femenino , Humanos , Masculino , Enfermedad de Parkinson/patología , Curva ROC , Índice de Severidad de la Enfermedad , Núcleo Subtalámico/fisiologíaRESUMEN
BACKGROUND: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. METHODS: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications. RESULTS: There was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the short-term (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure. CONCLUSIONS: Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society.
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Estimulación Encefálica Profunda/métodos , Mareo/terapia , Sistema de Registros , Temblor/terapia , Núcleos Talámicos Ventrales/fisiología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: Intraoperative magnetic resonance imaging (iMRI) is increasingly used to implant deep brain stimulator (DBS) electrodes. The approach has the advantages of a high targeting accuracy, minimization of brain penetrations, and allowance of implantation under general anesthesia. The hemorrhagic complications of iMRI-guided DBS implantation have not been studied in a large series. We report on the incidence and characteristics of hemorrhage during these procedures. METHODS: Hemorrhage incidence was assessed in a series of 231 iMRI procedures (374 electrodes implanted). All patients had movement disorders and the subthalamic nucleus or the globus pallidus internus was typically targeted. Hemorrhage was detected with intra- or postoperative MRI or postoperative computed tomography. Hemorrhage was classified based on its point of origin and clinical impact. RESULTS: Hemorrhage and symptomatic hemorrhage were detected during 2.4 and 1.1% of electrode implantations, respectively. The hemorrhage origin was subdural/subarachnoid (n = 3), subcortical (n = 5), or deep (n = 1). Factors that contributed to hemorrhage included unintentional crossing of a sulcus and resistance at the pial membrane, which produced cortical depression and a rebound hemorrhage. Delayed hemorrhage occurred in 2 patients and was attributed to premature reintroduction of anticoagulation therapy or air intrusion into the cranial cavity. CONCLUSIONS: Hemorrhage was readily apparent on intraoperative imaging, and hemorrhage rates for iMRI-guided DBS implantations were comparable to those for conventional implantation approaches.
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Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Estimulación Encefálica Profunda/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Adulto , Anciano , Estimulación Encefálica Profunda/métodos , Electrodos Implantados/efectos adversos , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/epidemiología , Trastornos del Movimiento/terapia , Tomografía Computarizada por Rayos XRESUMEN
The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop.
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Ritmo beta , Enfermedad de Parkinson/complicaciones , Corteza Sensoriomotora/fisiopatología , Núcleo Subtalámico/fisiopatología , Temblor/fisiopatología , Anciano , Sincronización Cortical , Electrocorticografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiopatología , Temblor/etiologíaRESUMEN
Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.