RESUMO
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most commonly used surgical treatment for Parkinson's disease (PD). The disease-modifying aspects of DBS at a cellular level are not fully understood, and the key question of the effect of DBS on the degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) remains to be answered. A major technical hurdle in determining any neuroprotective effect by DBS is its use in mid- to late-stage patients with PD when a majority of the DA neurons have been lost. In this work, we hypothesized that the long-term clinical benefits of DBS are, at least in part, due to a neuromodulatory effect on the SNpc neurons. These changes would affect cellular energetics and mitochondrial metabolism. We examined the number and volume of mitochondria as well as their vicinity to the DA presynaptic terminals postmortem caudate and putamen of 3 healthy individuals, 4 PD cases, and 3 DBS-treated patients. PD seems to have caused an increase in the mean distance between mitochondria and presynaptic terminals as well as a decrease in mean mitochondrial volume and numbers in DA projections. Although there was no difference in distance between mitochondria and presynaptic terminals of SNpc neurons in PD brains vs. DBS-treated brains, DBS treatment seemed to have inhibited or reversed the reduction in mitochondrial volume and numbers caused by PD. These results suggest enhanced metabolic plasticity leading to neuroprotection in the SNpc as a result of STN-DBS.-Mallach, A., Weinert, M., Arthur, J., Gveric, D., Tierney, T. S., Alavian, K. N. Post mortem examination of Parkinson's disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.
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Encéfalo/patologia , Estimulação Encefálica Profunda , Mitocôndrias/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Biomassa , Encéfalo/anatomia & histologia , Humanos , Terminações Pré-Sinápticas , SinapsesRESUMO
Rapid and flexible learning during behavioral choices is critical to our daily endeavors and constitutes a hallmark of dynamic reasoning. An important paradigm to examine flexible behavior involves learning new arbitrary associations mapping visual inputs to motor outputs. We conjectured that visuomotor rules are instantiated by translating visual signals into actions through dynamic interactions between visual, frontal and motor cortex. We evaluated the neural representation of such visuomotor rules by performing intracranial field potential recordings in epilepsy subjects during a rule-learning delayed match-to-behavior task. Learning new visuomotor mappings led to the emergence of specific responses associating visual signals with motor outputs in 3 anatomical clusters in frontal, anteroventral temporal and posterior parietal cortex. After learning, mapping selective signals during the delay period showed interactions with visual and motor signals. These observations provide initial steps towards elucidating the dynamic circuits underlying flexible behavior and how communication between subregions of frontal, temporal, and parietal cortex leads to rapid learning of task-relevant choices.
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Aprendizagem por Associação/fisiologia , Encéfalo/fisiologia , Neurônios/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Criança , Feminino , Lobo Frontal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Vias Neurais/fisiologia , Lobo Parietal/fisiologia , Estimulação Luminosa , Lobo Temporal/fisiologia , Percepção Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).
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Tremor Essencial/terapia , Tálamo/cirurgia , Terapia por Ultrassom , Atividades Cotidianas , Idoso , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Qualidade de Vida , Terapia por Ultrassom/efeitos adversos , Terapia por Ultrassom/métodos , Ultrassonografia de IntervençãoRESUMO
OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.
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Tremor Essencial/cirurgia , Imageamento por Ressonância Magnética/métodos , Procedimentos Neurocirúrgicos/métodos , Cirurgia Assistida por Computador/métodos , Tálamo/cirurgia , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Seguimentos , Transtornos Neurológicos da Marcha/complicações , Transtornos Neurológicos da Marcha/cirurgia , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Parestesia/complicações , Parestesia/cirurgia , Postura , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: To assess the likelihood of persistent postoperative pain (PPP) following reoperation after lumbar surgery and to estimate associated healthcare costs. METHODS: This is a retrospective cohort study using two linked UK databases: Hospital Episode Statistics and UK Clinical Practice Research Datalink. Costs and outcomes associated with reoperation were evaluated over a 2-year postoperative period using multivariate logistic regression for cases who underwent reoperation and controls who did not, based on demographics, index surgery type, smoking status, and pre-index comorbidities using propensity score matching. RESULTS: Risk factors associated with reoperation included younger age and the presence of diabetes with complications or rheumatic disease. The rate of PPP after reoperation was much higher than after index surgery, with 79 of 200 (39.5%; 95% CI 32.5%, 46.5%) participants experiencing ongoing pain compared with 983 of 5022 (19.5%; 95% CI 18.5%, 20.7%) after index surgery. Mean costs in the 2 years following reoperation were £1889 higher (95% CI £2, £3809) than for patients with PPP who did not undergo repeat surgery over an equivalent follow-up period. With the cost of reoperation itself included, the mean cost difference for patients who underwent reoperation compared with matched controls rose to £7221 (95% CI £5273, £9206). CONCLUSIONS: High rates of PPP and associated healthcare costs suggest that returning to the operating room is a complex and challenging decision. Spinal surgeons should review whether the potential benefits of additional surgery are justified when other approaches to managing and relieving chronic pain have demonstrated superior outcomes. These slides can be retrieved under Electronic Supplementary Material.
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Custos de Cuidados de Saúde/estatística & dados numéricos , Vértebras Lombares/cirurgia , Procedimentos Ortopédicos/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/economia , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Procedimentos Ortopédicos/economia , Dor Pós-Operatória/etiologia , Pontuação de Propensão , Reoperação/economia , Estudos Retrospectivos , Fatores de Risco , Reino UnidoRESUMO
BACKGROUND: There is currently no robust long-term data on costs of treating patients with Parkinson's disease. The objective of this study was to report levels of health care utilization and associated costs in the 10 years after diagnosis among PD patients in the United Kingdom. METHODS: We undertook a retrospective population-based cohort study using linked data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics databases. Total health care costs of PD patients were compared with those of a control group of patients without PD selected using 1:1 propensity score matching based on age, sex, and comorbidity. RESULTS: Between 1994 and 2013, 7271 PD patients who met study inclusion criteria were identified in linked Clinical Practice Research Datalink-Hospital Episode Statistics; 7060 were matched with controls. The mean annual health care cost difference (at 2013 costs) between PD patients and controls was £2471 (US$3716) per patient in the first year postdiagnosis (P < 0.001), increasing to £4004 (US$6021) per patient (P < 0.001) 10 years following diagnosis because of higher levels of use across all categories of health care utilization. Costs in patients with markers of advanced PD (ie, presence of levodopa-equivalent daily dose > 1100 mg, dyskinesias, falls, dementia, psychosis, hospital admission primarily due to PD, or nursing home placement) were on average higher by £1069 (US$1608) per patient than those with PD without these markers. CONCLUSIONS: This study provides comprehensive estimates of health care costs in PD patients based on routinely collected data. Health care costs attributable to PD increase in the year following diagnosis and are higher for patients with indicators of advanced disease. © 2018 International Parkinson and Movement Disorder Society.
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Atenção à Saúde/economia , Atenção à Saúde/métodos , Custos de Cuidados de Saúde/estatística & dados numéricos , Doença de Parkinson/economia , Doença de Parkinson/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Estudos de Coortes , Planejamento em Saúde Comunitária , Feminino , Humanos , Masculino , Doença de Parkinson/epidemiologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. OBJECTIVE: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. METHODS: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). RESULTS: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. CONCLUSION: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.
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Tremor Essencial , Imageamento por Ressonância Magnética , Doenças do Sistema Nervoso/etiologia , Complicações Pós-Operatórias/etiologia , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Ultrassonografia de Intervenção , Adulto , Estudos de Coortes , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estados UnidosRESUMO
Purpose To investigate the safety and targeting errors of deep-brain stimulation (DBS) electrodes placed under interventional magnetic resonance (MR) imaging, which allows near real-time anatomic placement without physiologic mapping. Materials and Methods Retrospectively evaluated were 10 consecutive patients (five women, five men) with a mean age of 59.9 years (age range, 17-79 years). These patients underwent interventional MR imaging-guided DBS placement for movement disorders from September 2013 to August 2014 for placement of 19 DBS electrodes in cases where traditional frame-based surgery may be challenging because of the following: dystonia resulting in difficulty in placing the patients in frame, patient's inability or unwillingness to tolerate awake surgery, or anatomic anomaly or variant that could increase the risk of bleeding from microelectrode mapping. Outcomes measured included perioperative hemorrhage, death, and stroke, and electrode functionality assessed at 2 weeks after the operation. In addition, the mean radial error and mean trajectory error were calculated. Results No intraoperative neurologic complications (n = 10 [95% confidence interval: 0%, 31%]) were observed. One patient developed aspiration pneumonia in the postoperative period. Mean radial error was 0.7 mm ± 0.4 (standard deviation) and mean trajectory error was 0.5 mm ± 0.4. All leads delivered clinically effective stimulation. Conclusion Interventional MR imaging-guided DBS electrode placement may be a safe and effective alternative to conventional frame-based surgery in well-selected patients. © RSNA, 2016.
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Estimulação Encefálica Profunda/instrumentação , Tremor Essencial/terapia , Doença de Parkinson/terapia , Adolescente , Adulto , Idoso , Eletrodos Implantados , Feminino , Humanos , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to analyze the impact of deep brain stimulation (DBS) of the posteromedial hypothalamus (pHyp) on seizure frequency in patients with drug-resistant epilepsy (DRE) associated with intractable aggressive behavior (IAB). METHODS: Data were collected retrospectively from nine patients, who received bilateral stereotactic pHyp-DBS for the treatment of medically intractable aggressive behavior, focusing on five patients who also had DRE. All patients were treated at the Colombian Center and Foundation of Epilepsy and Neurological Diseases-FIRE (Chapter of the International Bureau for Epilepsy), in Cartagena de Indias, Colombia from 2010 to 2014. Each case was evaluated previously by the institutional ethical committee, assessing the impact of aggressive behavior on the patient's family and social life, the humanitarian aspects of preserving the safety and physical integrity of caregivers, and the need to prevent self-harm. Epilepsy improvement was measured by a monthly seizure reduction percentage, comparing preoperative state and outcome. Additional response to epilepsy was defined by reduction of the antiepileptic drugs (AEDs). Aggressive behavior response was measured using the Overt Aggression Scale (OAS). RESULTS: All the patients with DRE associated with IAB presented a significant decrease of the rate of epileptic seizures after up to 4 years follow-up, achieving a general 89.6% average seizure reduction from the state before the surgery. Aggressiveness was significantly controlled, with evident improvement in the OAS, enhancing the quality of life of patients and families. SIGNIFICANCE: In well-selected patients, DBS of the pHyp seems to be a safe and effective procedure for treatment of DRE associated with refractory aggressive behavior. Larger and prospective series are needed to define the pHyp as a target for DRE in different contexts.
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Agressão/psicologia , Estimulação Encefálica Profunda , Hipotálamo Médio/fisiologia , Hipotálamo Posterior/fisiologia , Convulsões/psicologia , Convulsões/terapia , Adolescente , Adulto , Agressão/fisiologia , Estimulação Encefálica Profunda/tendências , Epilepsia/complicações , Epilepsia/psicologia , Epilepsia/terapia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Convulsões/complicações , Resultado do Tratamento , Adulto JovemRESUMO
Specific vulnerability and degeneration of the dopaminergic neurons in the substantia nigra pars compacta of the midbrain is the pathological hallmark of Parkinson's disease. A number of transcription factors regulate the birth and development of this set of neurons and some remain constitutively expressed throughout life. These maintenance transcription factors are closely associated with essential neurophysiological functions and are required ultimately for the long-term survival of the midbrain dopaminergic neurons. The current review describes the role of two such factors, Nurr1 and engrailed, in differentiation, maturation, and in normal physiological functions including acquisition of neurotransmitter identity. The review will also elucidate the relationship of these factors with life, vulnerability, degeneration and death of mesencephalic dopaminergic neurons in the context of Parkinson's disease.
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Neurônios Dopaminérgicos/metabolismo , Proteínas de Homeodomínio/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Doença de Parkinson/genética , Fatores de Transcrição/genética , Diferenciação Celular/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Mesencéfalo/metabolismo , Neurotransmissores/genética , Neurotransmissores/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Substância Negra/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Surgical therapy for treatment-resistant obsessive compulsive disorder (OCD) remains an effective option for well-selected patients managed within a multidisciplinary setting. Historically, lesions within the limbic system have been used to control both obsessive thoughts and repetitive compulsions associated with this disease. We discuss classical targets as well as contemporary neuromodulatory approaches that have been shown to provide symptomatic relief. Recently, deep brain stimulation (DBS) of the anterior limb of the internal capsule/ventral striatum received Conformité Européene (CE) mark and Food and Drug Administration (FDA) approvals for treatment of intractable OCD. Remarkably, this is the first such approval for neurosurgical intervention in a strictly psychiatric indication in modern times. This target is discussed in detail along with alternative targets currently being proposed. We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots. Further directions in the surgical treatment of OCD will require better preoperative predictors of postoperative responses, optimal selection of individualized targets, and rigorous reporting of adverse events and standardized outcomes. To meet these challenges, centers must be equipped with a multidisciplinary team and patient-centered approach to ensure adequate screening and follow up of patients with this difficult-to-treat condition.
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Estimulação Encefálica Profunda/métodos , Cápsula Interna/cirurgia , Transtorno Obsessivo-Compulsivo/terapia , Humanos , Transtorno Obsessivo-Compulsivo/cirurgiaRESUMO
The field of functional neurosurgery has developed a number of recent innovative neuromodulatory approaches to treat disease that remains resistant to the best medical therapy. These include novel surgical techniques to intervene in motor and cognitive sequelae of refractory epilepsy, neurodegenerative disease, and certain psychiatric conditions. To a large extent, much of the innovation in our field continues to be driven by a systems-level understanding of the impact of disease on the brain. For example, several groups have exploited findings from neuroimaging work to identify a number of new potential neuromodulatory targets for the treatment of refractory depression. Ongoing discoveries at the cellular and molecular level promise targeted gene or drug delivery aimed at curing disease. Neurosurgeons will certainly remain at the forefront of translating these strategies into practical clinical applications. Several randomized trials are now underway to assess the safety and efficacy of a number of new approaches, and we will continue to acquire better knowledge of optimal patient selection, identification of the most effective neuromodulatory targets, and recognition of adverse effects as these studies progress.
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Encefalopatias/terapia , Depressão/terapia , Procedimentos Neurocirúrgicos/métodos , Doença de Alzheimer/terapia , Epilepsia/terapia , Terapia Genética , Humanos , Doença de Huntington/terapia , Neurotransmissores , Optogenética , Doença de Parkinson/terapiaRESUMO
Surgical therapy for the secondary dystonias is generally perceived to be less effective than for primary disease. However, a number of case reports and small open series have recently appeared describing quite favorable outcomes following surgery for some nonprimary dystonias. We discuss surgical treatment options for this group of diverse conditions, including tardive dystonia, dystonic cerebral palsy, and certain heredodegenerative diseases in which deep brain stimulation and ablative lesions of the posteroventral pallidum have been shown to be effective. Other types of secondary dystonia respond less well to pallidal surgery, particularly when anatomical lesions of the basal ganglia are prominent on preoperative imaging. For these conditions, central baclofen delivery and botulinum toxin denervation may be considered. With optimal medical and surgical care, some patients with secondary dystonia have achieved reductions in disability and pain that approach those documented for primary dystonia.
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Distúrbios Distônicos/terapia , Neurocirurgia/métodos , Baclofeno/farmacologia , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/fisiologia , Toxinas Botulínicas/farmacologia , Denervação/métodos , Globo Pálido/efeitos dos fármacos , Globo Pálido/fisiologia , HumanosRESUMO
OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown. METHODS: The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children's Hospital in Miami, Florida, are presented. Patients 15-22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA). RESULTS: In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort. CONCLUSIONS: This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms.
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PURPOSE: To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery-commonly known as Failed Back Surgery Syndrome-and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy. METHODS: The UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24-month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP). RESULTS: Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy. CONCLUSIONS: Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within 2 years of surgery, the underlying indications for surgical modality and related choice of surgical procedure do not, by itself, appear to be a driving factor.
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Custos de Cuidados de Saúde , Procedimentos Ortopédicos/economia , Dor Pós-Operatória/economia , Doenças da Coluna Vertebral/economia , Medicina Estatal/economia , Estudos de Casos e Controles , Feminino , Seguimentos , Custos de Cuidados de Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/tendências , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/terapia , Doenças da Coluna Vertebral/epidemiologia , Doenças da Coluna Vertebral/cirurgia , Medicina Estatal/tendências , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
Most injuries to the neonatal brachial plexus occur acutely at birth, and are iatrogenic in origin. However, when weakness is accompanied by atrophy, nontraumatic etiologies should be considered. The differential diagnosis of chronic congenital brachial plexopathy includes cervical bone malformations, humeral osteomyelitis, varicella, and compression from various types of infantile tumors. An illustrative male infant delivered at 37 weeks of gestation with wasted musculature of the left upper arm, ipsilateral Horner's syndrome, and a hemidiaphragm is presented. On further examination, this patient manifested an underlying cervical tumor compressing the brachial plexus. Diagnostic steps leading to the pathologic identification of a solitary cervical myofibroma included physical examination, electromyography, radiographic imaging, and open biopsy. This report emphasizes the importance of differentiating acute from chronic congenital plexus palsy and of recognizing the possibility that infection or neoplasm may underlie the latter.
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Neuropatias do Plexo Braquial/diagnóstico , Miofibromatose/complicações , Paralisia/diagnóstico , Traumatismos do Braço/etiologia , Traumatismos do Braço/fisiopatologia , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Masculino , Miofibromatose/fisiopatologia , Paralisia/etiologia , Paralisia/fisiopatologia , GravidezRESUMO
Deep brain stimulation (DBS) has emerged as a revolutionary treatment option for essential tremor (ET), Parkinson's disease (PD), idiopathic dystonia, and severe obsessive-compulsive disorder (OCD). This article reviews the historical foundations of DBS including basal ganglia pathophysiological models, classic principles of electrical stimulation, technical components of the DBS system, treatment risks, and future directions for DBS. Chronic high frequency stimulation induces a number of functional changes from fast physiological to slower metabolic effects and ultimately leads to structural reorganization of the brain, so-called neuroplasticity. Examples of each of these fast, slow, and long-term changes are given in the context of Parkinson's disease where these mechanisms have perhaps been the most intensely investigated. In particular, details of striatal dopamine release, expression of trophic factors, and a possible neuroprotective mechanism of DBS are highlighted. We close with a brief discussion of technical and clinical considerations for improvement. Deep brain stimulation will continue to offer a reversible and safe therapeutic option for a host of neurological conditions and remains one of the best windows into human brain physiology.
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Estimulação Encefálica Profunda/métodos , Distonia/terapia , Tremor Essencial/terapia , Transtorno Obsessivo-Compulsivo/terapia , Doença de Parkinson/terapia , Gânglios da Base/fisiopatologia , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/tendências , Distonia/fisiopatologia , Estimulação Elétrica/métodos , Tremor Essencial/fisiopatologia , Previsões , Humanos , Vias Neurais/fisiologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Doença de Parkinson/fisiopatologiaRESUMO
OBJECTIVE: To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. DESIGN: Retrospective cohort study. SETTING: This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. PARTICIPANTS: 48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. RESULTS: The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). CONCLUSIONS: Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might have been considered.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Medicina Geral , Hipertensão/prevenção & controle , Adulto , Idoso , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: To characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery. DESIGN: Retrospective, population-based cohort study. SETTING: Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. PARTICIPANTS: Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD-HES. PRIMARY AND SECONDARY OUTCOMES MEASURES: Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery. RESULTS: The rate of individuals undergoing lumbar surgery in the CPRD-HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone. CONCLUSIONS: Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery.
Assuntos
Dor nas Costas/economia , Custos de Cuidados de Saúde , Região Lombossacral/cirurgia , Procedimentos Ortopédicos/efeitos adversos , Dor Pós-Operatória/economia , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Inglaterra , Feminino , Hospitais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/tendências , Dor Pós-Operatória/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring probe. The interstitial space of biological tissues and fluids is sampled through a thin fenestrated dialysis catheter inserted into the brain. The technique has been reported in patients with Parkinson's disease. However, the procedure is not widely used by neurosurgeons, possibly owing to unclear indications and poor effective benefits, mostly secondary to significant pitfalls. In spite of the feasibility of microdialysis in humans, many factors can affect the quality of the process. Possible pitfalls include improperly designed probe, probe insertion effects, ineffective perfusion rate, issues to optimize stabilization period, and insufficient volume sample. This article reviews those key technical features necessary for performing microdialysis in humans during deep brain stimulation for Parkinson's Disease.