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1.
J Neurosurg ; : 1-6, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38457788

ABSTRACT

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.

2.
Clin Neurol Neurosurg ; 237: 108150, 2024 02.
Article in English | MEDLINE | ID: mdl-38308938

ABSTRACT

OBJECTIVE: Osteodiscitis has been demonstrated to show significant morbidity and mortality. Cultures and CT guided biopsy (CTB) are commonly used diagnosis of osteodiscitis. This study's purpose is to evaluate the cost burden of CTB and to evaluate how IVDU affects patient management in the setting of osteodiscitis. METHODS: Patients admitted for osteodiscitis from 2011-2021 were retrospectively reviewed and stratified into cohorts by CTB status. Additional cohorts were stratified by Intravenous Drug Use (IVDU). Patient demographics, total cost of hospitalization, length of hospitalization, time to biopsy, IVDU status, and other factors were recorded. T-Test, Chi-squared analysis, and ANOVA were used for statistical analysis. RESULTS: Total cost of hospitalization was recorded for 140 patients without CTB and 346 patients with CTB. Average cost of hospitalization for non-CTB was $227,317.86 compared to CTB at $119,799.20 (p < 0.001). Length of stay (LOS) was found to be 18.01 days for non-CTB and 14.07 days for CTB patients (0.00282). When stratified by days until biopsy, patients who had CTB sooner, had significantly reduced cost of hospitalization (p = 0.0003). Patients with IVDU history were significantly younger (p < 0.001) with lower BMI (p < 0.001) and a significantly different clinical profile. There was a significant difference in positive open biopsy when separated by IVDU status (p = 0.025). CONCLUSION: CTB was associated with significantly reduced cost of hospitalization and LOS compared to non-CTB. IVDU patients with osteodiscitis have significantly different clinical profiles than non-IVDU that may impact diagnosis and treatment. Further work is indicated to elucidate causes of these differences to provide high value care to patients with osteodiscitis.


Subject(s)
Hospitalization , Image-Guided Biopsy , Humans , Retrospective Studies , Length of Stay , Tomography, X-Ray Computed
3.
J Neurosurg Spine ; 40(1): 99-106, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37890185

ABSTRACT

OBJECTIVE: Sagittal alignment is an important predictor of functional outcomes after surgery for adult spinal deformity (ASD). A rigid spinal column may create a large lever arm that may impact the rate of proximal junctional kyphosis (PJK) after ASD surgery. In this study, the authors sought to determine whether relatively low preoperative global spinal flexibility (i.e., rigid spine) predicts increased incidence of PJK at 1 year after ASD surgery. METHODS: The authors retrospectively reviewed long-segment thoracolumbar fusions with pelvic fixation performed at a single tertiary care center between October 2015 and September 2020 in patients with a minimum of 1-year radiographic and clinical follow-up. Two cohorts were established on the basis of the optimal value for spinal flexibility, as defined by the absolute difference between the preoperative standing and supine C7 sagittal vertical axes, which the authors termed global sagittal flexibility (GSF). Demographic information, radiographs, various associated complications, and patient-reported outcome measures (PROMs) were analyzed. RESULTS: Eighty-five patients met the inclusion criteria. Receiver operating characteristic (ROC) analysis using GSF to predict an increase in the proximal junctional sagittal Cobb angle (PJCA) greater than or equal to 10° at 1-year follow-up provided an area under the curve of 0.64 and identified an optimal GSF threshold value of 3.7 cm. Patients with GSF > 3.7 cm were considered globally flexible (48 patients), and those with GSF ≤ 3.7 cm were classified as rigid (37 patients). Rigid patients were noted to have a significantly higher risk of ΔPJCA ≥ 10° at 1-year follow-up (51.4% vs 29.3%, p = 0.049). No changes in the reoperation rates or PROMs based on GSF were observed in the 1- or 2-year postoperative window. CONCLUSIONS: Based on these retrospective data, preoperative global spinal rigidity portends an independently elevated risk for the development of PJK after ASD surgery. No differences in other complication rates or PROMs data were observed between groups. Data collection was limited to a 2-year postoperative window; therefore, longer follow-up is required to further elucidate the relationship between rigidity and reoperation rates. Based on these retrospective data, flexibility may influence the outcomes of patients with ASD.


Subject(s)
Kyphosis , Spinal Fusion , Adult , Humans , Retrospective Studies , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Kyphosis/diagnostic imaging , Kyphosis/surgery , Kyphosis/complications , Incidence , Neurosurgical Procedures/adverse effects , Spinal Fusion/adverse effects , Postoperative Complications/diagnostic imaging , Postoperative Complications/epidemiology , Postoperative Complications/etiology
4.
Int J Spine Surg ; 17(S3): S28-S34, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38135444

ABSTRACT

Formation of bony fusion after arthrodesis depends on osteoinduction, osteoconduction, and osteogenesis. Traditionally, the patient's own bone, or autograft, has been used to provide biological material necessary for these steps. However, the amount of autograft obtainable is often inadequate. Modern spine surgery has adopted the use of many autograft extenders or replacements, such as demineralized bone matrix or fibers. The present article covers the history of bone grafting, the production and technical details of demineralized bone matrix, and the evidence supporting its use in spine fusions.

5.
Brain Circ ; 9(1): 25-29, 2023.
Article in English | MEDLINE | ID: mdl-37151800

ABSTRACT

INTRODUCTION: Endovascular mechanical thrombectomy (EVT) has become the standard of care treatment for both intravenous tissue plasminogen activator eligible and ineligible patients presenting with an acute ischemic stroke due to a large vessel occlusion (LVO) within 24 h. Due to limited access to EVT, patients typically present to a non-EVT-capable center and are transferred to a larger, EVT-capable center. Quality improvement work has focused on improving this process to shorten the time to definitive recanalization of the affected vessel. MATERIALS AND METHODS: We retrospectively reviewed 98 consecutive patients who were transferred from an outside institution to our Comprehensive Stroke Center from July 2019 to September 2021. Thirty-nine of these patients had a diagnosed LVO at the transferring center on computed tomography angiography and were transferred directly to the angiography suite (DAT) whereas 59 patients were transferred to our Emergency Department for further imaging (EDT). Three of the patients in the DAT group did not undergo thrombectomy as there was no LVO identified on catheter angiography and were excluded from the study. RESULTS: Demographic and medical comorbidities were similar between the two groups. The DAT group had more severe strokes on presentation compared to the EDT group as measured by the National Institute of Health Stroke Severity (17.5 vs. 15, P = 0.048). Last known well (LKW) to arrival time in the angiography suite was significantly shorter in the DAT group (280 min vs. 474 min, P = 0.002). Patients in the DAT group were revascularized faster than the EDT group relative to LKW (320 min vs. 534 min, P < 0.001) while door-to-groin puncture and door-to-revascularization rates were similar. Modified Rankin score, incidence of symptomatic intracranial hemorrhage, and need for decompressive hemicraniectomy were similar between the two groups. Successful revascularization as measured by thrombolysis in cerebral infarction score occurred at a higher rate in the DAT group but was not statistical significance (97% vs. 85%, P = 0.055). DISCUSSION/CONCLUSION: DAT resulted in safe EVT compared to EDT with significant improvement in LKW to angiography suite presentation and subsequent vessel recanalization. Patients who underwent DAT experienced similar functional outcomes compared to EDT despite experiencing more severe strokes.

8.
Neurol Clin ; 40(2): 405-420, 2022 05.
Article in English | MEDLINE | ID: mdl-35465883

ABSTRACT

Familial neoplastic syndromes commonly impact the central and peripheral nervous systems. The most common neoplastic syndromes clinically relevant to neurology and neurologic surgery, include neurofibromatosis type 1, neurofibromatosis type 2, and Von Hippel-Lindau disease. We define the epidemiology, genetics, clinical presentation, and manifestations, as well as screening recommendations and management paradigms for these syndromes and other familial neoplastic syndromes that affect the nervous system. To ensure the optimal care of patients with neoplastic syndromes requires a multi-disciplinary approach and a comprehensive knowledge of the genetics, pathophysiology, manifestations, and management.


Subject(s)
Neoplastic Syndromes, Hereditary , Neurofibromatosis 1 , Tuberous Sclerosis , von Hippel-Lindau Disease , Humans , Neoplastic Syndromes, Hereditary/diagnosis , Neoplastic Syndromes, Hereditary/epidemiology , Neoplastic Syndromes, Hereditary/genetics , Neurofibromatosis 1/diagnosis , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/epidemiology , von Hippel-Lindau Disease/diagnosis , von Hippel-Lindau Disease/epidemiology , von Hippel-Lindau Disease/genetics
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 5860-5863, 2021 11.
Article in English | MEDLINE | ID: mdl-34892452

ABSTRACT

Calcium imaging has great potential to be applied to online brain-machine interfaces (BMIs). As opposed to two-photon imaging settings, a one-photon microendoscopic imaging device can be chronically implanted and is subject to little motion artifacts. Traditionally, one-photon microendoscopic calcium imaging data are processed using the constrained nonnegative matrix factorization (CNMFe) algorithm, but this batched processing algorithm cannot be applied in real-time. An online analysis of calcium imaging data algorithm (or OnACIDe) has been proposed, but OnACIDe updates the neural components by repeatedly performing neuron identification frame-by-frame, which may decelerate the update speed if applying to online BMIs. For BMI applications, the ability to track a stable population of neurons in real-time has a higher priority over accurately identifying all the neurons in the field of view. By leveraging the fact that 1) microendoscopic recordings are rather stable with little motion artifacts and 2) the number of neurons identified in a short training period is sufficient for potential online BMI tasks such as cursor movements, we proposed the short-training CNMFe algorithm (stCNMFe) that skips motion correction and neuron identification processes to enable a more efficient BMI training program in a one-photon microendoscopic setting.


Subject(s)
Brain-Computer Interfaces , Algorithms , Artifacts , Calcium , Photons
10.
Cell Rep ; 35(11): 109239, 2021 06 15.
Article in English | MEDLINE | ID: mdl-34133921

ABSTRACT

Microendoscopic calcium imaging with one-photon miniature microscopes enables unprecedented readout of neural circuit dynamics during active behavior in rodents. In this study, we describe successful application of this technology in the rhesus macaque, demonstrating plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from large populations of neurons simultaneously in bilateral dorsal premotor cortices during performance of a naturalistic motor reach task. Imaging is stable over several months, allowing us to longitudinally track individual neurons and monitor their relationship to motor behavior over time. We observe neuronal calcium dynamics selective for reach direction, which we could use to decode the animal's trial-by-trial motor behavior. This work establishes head-mounted microendoscopic calcium imaging in macaques as a powerful approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and it promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.


Subject(s)
Behavior, Animal/physiology , Calcium/metabolism , Endoscopy , Imaging, Three-Dimensional , Motor Cortex/diagnostic imaging , Animals , Head , Macaca mulatta , Male , Motor Cortex/surgery , Neurons/physiology , Time Factors
12.
J Surg Res ; 257: 519-528, 2021 01.
Article in English | MEDLINE | ID: mdl-32919342

ABSTRACT

BACKGROUND: Cholecystectomy is considered a low-risk procedure with proven safety in many high-risk patient populations. However, the risk of cholecystectomy in patients with active cancer has not been established. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried to identify all patients with disseminated cancer who underwent cholecystectomy from 2005 to 2016. Postcholecystectomy outcomes were defined for patients with cancer and those without by comparing several outcomes measures. A multivariate model was used to estimate the odds of 30-d mortality. RESULTS: We compared outcomes in 3097 patients with disseminated cancer to a matched cohort of patients without cancer. Patients with cancer had more comorbidities at baseline: dyspnea (10.5% versus 7.0%, P < 0.0001), steroid use (10.1% versus 3.0%, P < 0.0001), and loss of >10% body weight in 6-mo prior (9.3% versus 1.6%, P < 0.0001). Patients with cancer sustained higher rates of wound (2.3% versus 5.6%, P < 0.0001), respiratory (1.4% versus 3.9%, P < 0.0001), and cardiovascular (2.0% versus 6.8%, P < 0.0001) complications. In addition, patients with disseminated cancer experienced a longer length of stay and higher 30-d mortality. Multivariate modeling showed that the odds of 30-d mortality was 3.3 times greater in patients with cancer. CONCLUSIONS: Compared to patients without cancer, those with disseminated cancer are at higher risk of complication and mortality following cholecystectomy. Traditional treatment algorithms should be used with caution and care decisions individualized based on the patient's disease status and treatment goals.


Subject(s)
Cholecystectomy, Laparoscopic/mortality , Cholecystitis/surgery , Neoplasms/complications , Postoperative Complications/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cholecystitis/complications , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Quality Improvement , Retrospective Studies , Risk Assessment , United States/epidemiology , Young Adult
13.
Surg Neurol Int ; 11: 20, 2020.
Article in English | MEDLINE | ID: mdl-32123608

ABSTRACT

BACKGROUND: Atlantoaxial pseudoarticulation rarely involves the cervical spine, and its etiology is unclear. In theory, pseudoarticulation is comparable to Bertolotti's syndrome in the lumbar spine or may be attributed to an aberrant focal fusion between C0-C1-C2 that occurs during the gastrulation of embryologic development. CASE DESCRIPTION: A 39-year-old female presented with neck pain and upper extremity weakness. Magnetic resonance/computed tomography studies documented a left-sided unilateral pseudoarticulation between the lamina of C1 and C2 causing compression of the dorsal spinal cord. Following resection of the accessory C1/C2 joint utilizing a C1 hemilaminectomy and partial C2 laminectomy, the patient's neck pain and weakness resolved. Histologically, the tissue showed benign osteocartilaginous tissue with no synovial capsule. CONCLUSION: Here, the authors present a case of occiput-C1-C2 pseudojoint formation, leading to clinical and radiographic findings of cord compression due to boney outgrowth.

14.
Brain Circ ; 6(1): 31-37, 2020.
Article in English | MEDLINE | ID: mdl-32166198

ABSTRACT

OBJECTIVE: Incomplete circle of Willis (CoW) configuration is an important risk factor for cerebrovascular pathology, namely aneurysm formation and ischemic stroke. This study was performed to characterize CoW variation using digital subtraction angiography and to identify demographic and physiologic features that may influence the risk of having an incomplete CoW configuration. MATERIALS AND METHODS: A retrospective review of 274 patients who underwent cerebral angiography by a single surgeon for any indication was conducted. Each CoW branch was graded as normal, hypoplastic, or aplastic. Univariate and multivariate regression analyses were conducted to assess the impact of age, gender, race, and certain comorbidities on CoW configuration. RESULTS: A complete CoW was identified in 37.23% of patients. In univariate analysis, patients <40 years old were more likely to have a complete CoW (odds ratio [OR]: 4.973, 95% confidence interval [CI]: 2.610-9.476, P < 0.001) as were patients <70 years old (OR: 2.849, 95% CI: 1.131-7.194, P < 0.05). Univariate analysis on demographic factors and comorbidities revealed CoW completeness to decrease with hypertension (OR: 0.575, 95% CI: 0.347-0.951, P = 0.031) and diabetes mellitus (OR: 0.368, 95% CI: 0.180-0.754, P = 0.006). Multivariable logistic regression analysis used to assess the impact of age on CoW completeness showed age to be an independent predictor of complete CoW, with an inverse correlation between increasing age and CoW completeness (OR: 0.955, 95% CI: 0.937-0.973, P < 0.001) after controlling for potential confounders including hypertension and diabetes mellitus. CONCLUSIONS: CoW configuration shows considerable variation with age; however, further investigation is required to elucidate the full impact of other demographic and vascular risk factors on CoW anatomy.

15.
World Neurosurg ; 135: e494-e499, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31843729

ABSTRACT

OBJECTIVE: The rapid processing of perfusion and diffusion (RAPID) system for automating perfusion and diffusion data from head computed tomography has improved acute ischemic stroke treatment by quickly and accurately identifying those patients who may benefit from thrombectomy. Collateral scoring (CS) of cerebral arteries using computed tomography angiography (CTA) has proven useful in predicting postintervention infarct volumes and functional outcomes in ischemic stroke patients. Here we evaluate the relationship between CS and RAPID software in an effort to augment triage and provide improved predictability of functional outcomes in ischemic stroke patients. METHODS: A retrospective review of 77 mechanical thrombectomy patients from January 2017 to October 2018 with large vessel occlusions of the anterior circulation who underwent RAPID and CTA imaging was performed. Baseline characteristics, RAPID data, CS, modified Rankin Scale score, and procedural data were collected. magnetic resonance imaging was used to calculate the postintervention stroke volume. RESULTS: CS inversely correlates with the volume of RAPID cerebral blood flow <30% (ß= -18.131, 95% confidence interval [CI] -24.384 to -11.879, P < 0.001), RAPID Tmax >6s (ß= -22.205, 95% CI -39.125 to -5.285, P = 0.011), postintervention stroke volume (ß= -30.637, 95% CI -41.554 to -19.720, P < 0.001), and discharge National Institutes of Health Stroke Scale score (ß= -1.922, 95% CI -3.575 to -0.269, P = 0.023). CONCLUSIONS: CS on CTA may be a useful way to identify patients who would benefit from mechanical thrombectomy and predict functional outcomes postintervention. CS may allow the stroke team to optimize the care of patients who may not be able to obtain RAPID analysis.


Subject(s)
Brain Ischemia/surgery , Collateral Circulation/physiology , Middle Cerebral Artery/physiology , Stroke/surgery , Thrombectomy , Adult , Aged , Anticoagulants/therapeutic use , Brain Ischemia/physiopathology , Cerebrovascular Circulation/physiology , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Stroke/physiopathology , Tomography, X-Ray Computed , Treatment Outcome
16.
Int J Pediatr Otorhinolaryngol ; 116: 65-69, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30554710

ABSTRACT

BACKGROUND: Endoscopic airway measurement (EAM) combines optical endoscopic instruments with open source image processing to accurately obtain airway dimensions. Preclinical models have demonstrated EAM as an accurate technique of airway measurement with the added advantage of characterizing multilevel stenosis, non-circular lesions, and distal obstruction. The aim of this prospective clinical study was to compare EAM to airway measurements obtained from endotracheal tube approximation (ETTA) during pediatric aerodigestive evaluation and to evaluate reproducibility of EAM across practitioners. METHODS: Thirty-seven pediatric patients undergoing routine microlaryngoscopy and bronchoscopy at a single tertiary care children's hospital were prospectively recruited. Patients undergoing emergent procedures were excluded. Two blinded reviewers performed airway measurements using ImageJ (NIH) as previously described and average values were compared to ETTA measurements. Additional EAMs were obtained from an ex vivo airway model by 28 separate clinicians and were analyzed by the same reviewers to evaluate reproducibility. RESULTS: EAM and ETTA measurements were themselves significantly different (p = 0.0003); however, the average absolute difference between the two methods was small (Mean: 0.5 mm, 95%CI: -2.6-1.6 mm). There were notable differences between raters such that estimates of raters with more experience were more similar to ETTA. Despite observed differences between EAM and ETTA, endoscopic airway measurement was highly correlated with ETTA (p = 0.0002, Spearman r = 0.4185), and strong agreement was observed (Bias: -0.4974 ±â€¯1.083 mm, 95% LOA: -2.62-1.625 mm). CONCLUSION: Clinical use of EAM is a valid and precise approach for quantification of airway luminal dimensions. This method may provide advantages over traditional ETTAs for evaluation of asymmetric airway morphology in the pediatric population.


Subject(s)
Bronchoscopy/methods , Intubation, Intratracheal/methods , Laryngoscopy/methods , Respiratory System/surgery , Adolescent , Child , Child, Preschool , Female , Humans , Image Processing, Computer-Assisted , Infant , Male , Prospective Studies , Reproducibility of Results
17.
J Neurophysiol ; 117(3): 1112-1125, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28031396

ABSTRACT

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust.NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI.


Subject(s)
Conditioning, Operant/physiology , Motor Cortex/physiology , Neurons/physiology , Nucleus Accumbens/physiology , Reinforcement, Psychology , Action Potentials , Animals , Electric Stimulation , Electromyography , Macaca nemestrina , Male , Reward , Upper Extremity/physiology
18.
Neuron ; 80(5): 1301-9, 2013 Dec 04.
Article in English | MEDLINE | ID: mdl-24210907

ABSTRACT

Motor learning and functional recovery from brain damage involve changes in the strength of synaptic connections between neurons. Relevant in vivo evidence on the underlying cellular mechanisms remains limited and indirect. We found that the strength of neural connections between motor cortex and spinal cord in monkeys can be modified with an autonomous recurrent neural interface that delivers electrical stimuli in the spinal cord triggered by action potentials of corticospinal cells during free behavior. The activity-dependent stimulation modified the strength of the terminal connections of single corticomotoneuronal cells, consistent with a bidirectional spike-timing-dependent plasticity rule previously derived from in vitro experiments. For some cells, the changes lasted for days after the end of conditioning, but most effects eventually reverted to preconditioning levels. These results provide direct evidence of corticospinal synaptic plasticity in vivo at the level of single neurons induced by normal firing patterns during free behavior.


Subject(s)
Action Potentials/physiology , Motor Neurons/physiology , Neuronal Plasticity/physiology , Pyramidal Tracts/cytology , Pyramidal Tracts/physiology , Wakefulness/physiology , Analysis of Variance , Animals , Biophysics , Circadian Rhythm , Electric Stimulation , Electromyography , Macaca nemestrina , Male , Nerve Net/physiology , Neural Inhibition/physiology , Time Factors
19.
Mov Disord ; 28(9): 1257-62, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23630185

ABSTRACT

Our previous studies in Parkinson's disease have shown that both levodopa and expectancy of receiving levodopa reduce cortical excitability. We designed this study to evaluate how degree of expectancy and other individual factors modulate placebo response in Parkinson's patients. Twenty-six Parkinson's patients were randomized to 1 of 3 groups: 0%, 50%, and 100% expectancy of receiving levodopa. All subjects received placebo regardless of expectancy group. Subjects completed the NEO-Five Factor Inventory, General Perceived Self-Efficacy Scale, and Perceived Stress Scale. Cortical excitability was measured by the amplitude of motor-evoked potential (MEP) evoked by transcranial magnetic stimulation. Objective physical fatigue of extensor carpi radialis before and after placebo levodopa was also measured. Responders were defined as subjects who responded to the placebo levodopa with a decrease in MEP. Degree of expectancy had a significant effect on MEP response (P < .05). Subjects in the 50% and 100% expectancy groups responded with a decrease in MEP, whereas those in the 0% expectancy group responded with an increase in MEP (P < .05). Responders tended to be more open to experience than nonresponders. There were no significant changes in objective physical fatigue between the expectancy groups or between responders and nonresponders. Expectancy is associated with changes in cortical excitability. Further studies are needed to examine the relationship between personality and placebo effect in Parkinson's patients. © 2013 Movement Disorder Society.


Subject(s)
Cerebral Cortex/physiopathology , Evoked Potentials, Motor/physiology , Motivation/physiology , Parkinson Disease , Personality/physiology , Aged , Aged, 80 and over , Analysis of Variance , Antiparkinson Agents/therapeutic use , Cerebral Cortex/drug effects , Double-Blind Method , Fatigue/etiology , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Motor Activity/physiology , Parkinson Disease/drug therapy , Parkinson Disease/pathology , Parkinson Disease/psychology , Personality Inventory , Surveys and Questionnaires
20.
Clin Neuropharmacol ; 32(6): 305-10, 2009.
Article in English | MEDLINE | ID: mdl-19620846

ABSTRACT

BACKGROUND: Fatigue is a major nonmotor symptom in Parkinson disease(PD). It is associated with reduced activity and lower quality of life. OBJECTIVE: To determine if modafinil improves subjective fatigue and physical fatigability in PD. METHODS: Nineteen PD patients who reported significant fatigue in the Multidimensional Fatigue Inventory (MFI) participated in this 8-week study. Subjects took their regular medications and were randomly assigned to the treatment group (9 subjects, modafinil 100-mg capsule BID) or placebo group (10 subjects). We used the MFI to measure subjective fatigue and used finger tapping and intermittent force generation to evaluate physical fatigability. Subjects also completed the Epworth Sleepiness Scale (ESS) and the Center of Epidemiological Study-Depression Scale. RESULTS: There were no significant differences at baseline and at 1 month in finger tapping and ESS between the modafinil and placebo groups. At 2 months, the modafinil group had a higher tapping frequency (P<0.05), shorter dwell time (P<0.05), and less fatigability in finger tapping and tended to have lower ESS scores (P<0.12) than the placebo group. However, there was no difference between groups over time for any dimension of the MFI . CONCLUSIONS: This small study demonstrated that although modafinil may be effective in reducing physical fatigability in PD, it did not improve fatigue symptoms.


Subject(s)
Benzhydryl Compounds/therapeutic use , Central Nervous System Stimulants/therapeutic use , Fatigue/drug therapy , Parkinson Disease/drug therapy , Aged , Aged, 80 and over , Depression/drug therapy , Depression/etiology , Depression/physiopathology , Double-Blind Method , Fatigue/etiology , Fatigue/physiopathology , Female , Fingers/physiopathology , Humans , Male , Middle Aged , Modafinil , Neuropsychological Tests , Parkinson Disease/complications , Parkinson Disease/physiopathology , Pilot Projects , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Quality of Life , Severity of Illness Index , Sleep Wake Disorders/drug therapy , Sleep Wake Disorders/etiology , Sleep Wake Disorders/physiopathology , Time Perception/drug effects , Time Perception/physiology , Treatment Outcome
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