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OBJECTIVE: Advancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system. MATERIALS AND METHODS: We analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states. RESULTS: Overall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, ß peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative ß band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG. CONCLUSIONS: For this patient, an increase in ß band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.
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Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.
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Biomarcadores , Traumatismos por Explosões , Concussão Encefálica , Sistema Glinfático , Veteranos , Humanos , Masculino , Traumatismos por Explosões/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Adulto , Estudos Transversais , Estudos Retrospectivos , Concussão Encefálica/líquido cefalorraquidiano , Concussão Encefálica/diagnóstico por imagem , Feminino , Sistema Glinfático/diagnóstico por imagem , Estados Unidos , Campanha Afegã de 2001- , Guerra do Iraque 2003-2011 , Pessoa de Meia-Idade , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: Interspinous process devices (IPDs) were developed as minimally invasive alternatives to open decompression surgery for spinal stenosis. However, given high treatment failure and reoperation rates, there has been minimal adoption by spine surgeons. This study leveraged a national claims database to characterize national IPD usage patterns and postoperative outcomes after IPD implantation. METHOD: Using the PearlDiver database, we identified all patients who underwent 1- or 2-level IPD implantation between 2010 and 2018. Univariate and multivariable logistic regression was performed to identify predictors of the number of IPD levels implanted and reoperation up to 3 years after the index surgery. Right-censored Kaplan-Meier curves were plotted for duration of reoperation-free survival and compared with log-rank tests. RESULTS: Patients (n = 4865) received 1-level (n = 3246) or 2-level (n = 1619) IPDs. Patients who were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.01-1.03, P < .001), male (aOR 1.31, 95% CI 116-1.50, P < .001), and obese (aOR 1.19, 95% CI 1.05-1.36, P < .01) were significantly more likely to receive a 2-level IPD than to receive a 1-level IPD. The 3-year reoperation rate was 9.3% of patients when mortality was accounted for during the follow-up period. Older age decreased (aOR 0.97, 95% CI 0.97-0.99, P = .0039) likelihood of reoperation, whereas 1-level IPD (aOR 1.37, 95% CI 1.01-1.89, P = .048), Charlson Comorbidity Index (aOR 1.07, 95% CI 1.01-1.14, P = .018), and performing concomitant open decompression increased the likelihood of reoperation (aOR 1.68, 95% CI 1.35-2.09, P = .0014). CONCLUSION: Compared with 1-level IPDs, 2-level IPDs were implanted more frequently in older, male, and obese patients. The 3-year reoperation rate was 9.3%. Concomitant open decompression with IPD placement was identified as a significant risk factor for subsequent reoperation and warrants future investigation.
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Descompressão Cirúrgica , Estenose Espinal , Humanos , Masculino , Idoso , Reoperação , Vértebras Lombares/cirurgia , Estenose Espinal/cirurgia , Estenose Espinal/etiologia , Fatores de Risco , Obesidade , Resultado do TratamentoRESUMO
OBJECTIVE: Bone morphogenetic protein (BMP) has been increasingly used in spinal surgery to promote arthrodesis. Because BMP stimulates cellular proliferation, its association with tumorigenesis is a concern. Previous research has generated conflicting conclusions on the risk of cancer in patients receiving BMP. The authors aimed to compare the incidence of solid organ and hematopoietic malignancies in patients undergoing spinal arthrodesis with or without BMP. METHODS: The PearlDiver Mariner Patient Claims Database was queried for patients undergoing thoracolumbar fusion between 2015 and 2021. Patients with preexisting malignancy were excluded. Data were analyzed for incidence of solid organ malignancy and hematopoietic malignancy diagnosed after spinal surgery. Propensity score matching using age, sex, tobacco usage, and year of surgery was performed between patients who did and those who did not receive BMP. RESULTS: Among patients without prior solid organ malignancy, BMP was used in 22,139 patients and not used in 306,249. In the propensity score-matched group, 3.1% of the BMP group developed solid organ malignancy following surgery compared with 3.5% in the non-BMP group. The relative risk (RR) of developing solid organ malignancy after BMP exposure was 0.89 (95% CI 0.81-0.98, p = 0.02). Among patients without prior hematopoietic malignancy, BMP was used in 23,505 patients and not used in 328,796 patients. In the propensity score-matched group, 0.4% of the BMP group developed hematopoietic malignancy compared with 0.6% of the non-BMP group. The RR of developing hematopoietic malignancy after BMP exposure was 0.71 (95% CI 0.55-0.93, p = 0.015). CONCLUSIONS: BMP use in thoracolumbar fusion was not associated with an increased risk of new malignancy, which further supports emerging data on the lack of an association between BMP use and increased malignancy.
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Neoplasias Hematológicas , Neoplasias , Fusão Vertebral , Humanos , Fusão Vertebral/efeitos adversos , Pontuação de Propensão , Proteínas Morfogenéticas Ósseas/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/cirurgia , Neoplasias Hematológicas/induzido quimicamente , Proteína Morfogenética Óssea 2/efeitos adversosRESUMO
OBJECTIVE: Stereotactic electroencephalography (sEEG) is an increasingly utilized method for identifying electrophysiological processes underlying sensorimotor, cognitive, and emotional behaviors. In this review, the authors outline current research using sEEG to investigate the neural activity underlying emotional and psychiatric behaviors. Understanding the current structure of intracranial research using sEEG will inform future studies of psychiatric disease and therapeutics for effective neuromodulation. METHODS: The authors conducted a comprehensive systematic review of studies according to PRISMA guidelines to investigate behaviors related to psychiatric conditions in patients with epilepsy undergoing monitoring with sEEG. Articles indexed on PubMed between 2010 and 2022 were included if they studied emotions or affective behaviors or met the National Institute of Mental Health Research Domain Criteria positive and negative valence domains. Data extracted from articles included study sample size, paradigms and behavioral tasks employed, cortical and subcortical targets, EEG analysis methods, and identified electrophysiological activity underlying the studied behavior. The Newcastle-Ottawa Scale was used to assess bias risk. RESULTS: Thirty-two primary articles met inclusion criteria. Study populations ranged from 3 to 39 patients. The most common structures investigated were the amygdala, insula, orbitofrontal cortex (OFC), hippocampus, and anterior cingulate cortex (ACC). Paradigms, stimuli, and behavioral tasks widely varied. Time-frequency analyses were the most common, followed by connectivity analyses. Multiple oscillations encoded a variety of behaviors related to emotional and psychiatric conditions. High gamma activity was observed in the amygdala and anterior insula in response to aversive audiovisual stimuli and in the OFC in response to reward processing. ACC beta band power increases and hippocampal-amygdala beta coherence variations were predictive of worsening mood states. Insular and amygdalar theta oscillations encoded social pain and fear learning, respectively. Most studies performed passing recordings, allowing for the decoding of affective states and depression symptoms, while other studies utilized direct stimulation, such as in the OFC to improve mood symptoms. CONCLUSIONS: Stereotactic EEG in epilepsy has identified multiple corticolimbic structures with specific oscillatory and synchronization activity underlying a diverse range of behaviors related to emotions and affective conditions. Given the heterogeneity of psychiatric conditions, sEEG provides an opportunity to study these neural correlates to develop personalized effective neuromodulatory treatments. Future studies should focus on optimizing paradigms and tasks to investigate a broad range of behavioral phenotypes that overlap across psychiatric conditions.
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Emoções , Epilepsia , Humanos , Emoções/fisiologia , Eletroencefalografia/métodos , Epilepsia/cirurgia , Córtex Pré-Frontal , MedoRESUMO
PURPOSE OF REVIEW: Deep brain stimulation (DBS) for chronic pain has been controversial. Despite the discouraging outcomes from multicenter clinical trial in the twentieth century, there is sustained interest in optimizing its use to improve patient outcomes. Here we provide a concise overview of DBS for chronic pain as a reference for clinicians. RECENT FINDINGS: Recently published data lends tentative support for DBS as a means of treating chronic pain. Still, high level-of-evidence data remain elusive. There are a handful of ongoing and prospective clinical trials exploring DBS for pain in the context of closed-loop neuromodulation, invasive electroencephalography monitoring, stimulation parameters, and novel intracranial targets. DBS is a potentially viable method of treating chronic pain. Procedure success is dependent on a number of factors including proper patient and intracranial target selection. Outcomes for ongoing and future clinical trials will help clinicians refine DBS use for this clinical indication.
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Dor Crônica , Estimulação Encefálica Profunda , Humanos , Estimulação Encefálica Profunda/métodos , Dor Crônica/terapia , Estudos Prospectivos , Encéfalo , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND CONTEXT: The rate of surgical site infection (SSI) following elective spine surgery ranges from 0.5%â10%. Published reports suggest a higher SSI rate in non-elective spine surgery such as spine trauma; however, there is a paucity of large database studies examining this issue. PURPOSE: The objective of this study was to investigate the incidence and risk factors of SSI in patients undergoing spine surgery for thoracic and lumbar fractures in a large population database. STUDY DESIGN/SETTING: This is a retrospective study utilizing the PearlDiver Patient Claims Database. PATIENT SAMPLE: Patients undergoing spine surgery for thoracic and lumbar fractures between 2015-2020 were identified in the PearlDiver Patient Claims Database using ICD-10 codes. Patients were excluded who had another surgery either 14 days before or 21 days after the index spine surgery, or pathologic fracture. OUTCOME MEASURES: Rate of surgical site infection. METHODS: Clinical data collected from the PearlDiver database based on ICD-10 codes included gender, age, diabetes, smoking status, obesity, Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI), and SSI. Univariate analysis was used to assess the association of potential risk factors and SSI. Multivariable analysis was used to identify independent risk factors of SSI. The authors have no conflicts of interest or funding sources to declare. RESULTS: A total of 11,401 patients undergoing spine surgery for thoracic and lumbar fractures met inclusion criteria, and 1,065 patients were excluded. 860 patients developed SSI (7.5%). Risk factors significantly associated with SSI in univariate analysis included diabetes (OR 1.50; 95% CI, 1.30â1.73; p<.001), obesity (OR 1.66; 95% CI, 1.44â1.92; p<.001), increased age (p<.001), ECI (p<.001), and CCI (p<.001). On multivariable analysis, obesity and ECI were independently associated with SSI (p<.001 and p<.001, respectively). CONCLUSIONS: Non-elective surgery for thoracic and lumbar fractures is associated with a 7.5% risk of SSI. Obesity and ECI are independent predictors of SSI in this population. Limitations include the reliance on accurate insurance coding which may not fully capture all SSI, and in particular superficial SSI. These findings provide a broad overview of the risk of SSI in this population at a national level and may also help counsel patients regarding risk.
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Fraturas da Coluna Vertebral , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Incidência , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/complicações , Obesidade/complicaçõesRESUMO
BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.
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COVID-19 , Pseudotumor Cerebral , Humanos , Feminino , Masculino , Pseudotumor Cerebral/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Unidades de Terapia Intensiva , Atenção à Saúde , Estudos RetrospectivosRESUMO
Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren's syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.
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Linfócitos B/efeitos dos fármacos , Colecalciferol/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/sangue , Adulto , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Camundongos , Deficiência de Vitamina D/sangueRESUMO
BACKGROUND: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. OBJECTIVE: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. METHODS: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. RESULTS: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores. CONCLUSION: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation.
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Dor Crônica/terapia , Estimulação Encefálica Profunda/métodos , Neuroestimuladores Implantáveis , Manejo da Dor/métodos , Dor Intratável/terapia , Dor Crônica/diagnóstico , Dor Crônica/psicologia , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/tendências , Feminino , Humanos , Neuroestimuladores Implantáveis/tendências , Masculino , Manejo da Dor/instrumentação , Dor Intratável/diagnóstico , Dor Intratável/psicologia , Membro Fantasma/diagnóstico , Membro Fantasma/psicologia , Membro Fantasma/terapia , Qualidade de Vida/psicologia , Tálamo/fisiologiaRESUMO
There is increasing recognition of the role the microbiome plays in states of health and disease. Microbiome studies in systemic autoimmune diseases demonstrate unique microbial patterns in Inflammatory Bowel Disease, Rheumatoid Arthritis, and Systemic Lupus Erythematosus to a lesser extent, whereas there is no single bug or pattern that characterizes Multiple Sclerosis. Autoimmune diseases tend to share a predisposition for vitamin D deficiency, which alters the microbiome and integrity of the gut epithelial barrier. In this review, we summarize the influence of intestinal bacteria on the immune system, explore the microbial patterns that have emerged from studies on autoimmune diseases, and discuss how vitamin D deficiency may contribute to autoimmunity via its effects on the intestinal barrier function, microbiome composition, and/or direct effects on immune responses.
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Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Microbioma Gastrointestinal , Vitamina D/imunologia , Animais , Doenças Autoimunes/genética , Autoimunidade , HumanosRESUMO
Distinct mutations in the centrosomal-cilia protein CEP290 lead to diverse clinical findings in syndromic ciliopathies. We show that CEP290 localizes to the transition zone in ciliated cells, precisely to the region of Y-linkers between central microtubules and plasma membrane. To create models of CEP290-associated ciliopathy syndromes, we generated Cep290(ko/ko) and Cep290(gt/gt) mice that produce no or a truncated CEP290 protein, respectively. Cep290(ko/ko) mice exhibit early vision loss and die from hydrocephalus. Retinal photoreceptors in Cep290(ko/ko) mice lack connecting cilia, and ciliated ventricular ependyma fails to mature. The minority of Cep290(ko/ko) mice that escape hydrocephalus demonstrate progressive kidney pathology. Cep290(gt/gt) mice die at mid-gestation, and the occasional Cep290(gt/gt) mouse that survives shows hydrocephalus and severely cystic kidneys. Partial loss of CEP290-interacting ciliopathy protein MKKS mitigates lethality and renal pathology in Cep290(gt/gt) mice. Our studies demonstrate domain-specific functions of CEP290 and provide novel therapeutic paradigms for ciliopathies.