Shivanand P. Lad

Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment

Alterations in synaptic protein stoichiometry may contribute to neocortical synaptic dysfunction in Alzheimer disease (AD). Whether perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remain unclear. We examined protein levels of synaptophysin (SYP), synaptotagmin (SYT), and drebrin (DRB) in 5 neocortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual) of people clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Normalized SYP levels were decreased approximately 35% in the superior temporal and inferior parietal cortex in severe AD compared with NCI. SYT levels were unchanged across clinical diagnosis in the cortical regions. Levels of DRB, a dendritic spine plasticity marker, were reduced approximately 40% to 60% in all cortical regions in AD compared with NCI. DRB protein was also reduced approximately 35% in the superior temporal cortex of MCI subjects, and DRB and SYP levels in the superior temporal cortex correlated with Mini-Mental State Examination and Braak scores. In contrast, DRB levels in the superior frontal cortex increased approximately 30% in MCI subjects. The differential changes in DRB expression in the frontal and temporal cortex in MCI suggest a disparity of dendritic plasticity within these regions that may contribute to the early impairment of temporal cortical functions subserving memory and language compared with the relative preservation of frontal cortical executive function during the initial stages of cognitive decline.

Risk Factors for Postoperative Spinal Wound Infections After Spinal Decompression and Fusion Surgeries

Study Design. This is a multivariate analysis of a prospectively collected database. Objective. To determine preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery. Summary of Background Data. Current literature sites a postoperative infection rate of approximately 4%; however, few have completed multivariate analysis to determine factors which contribute to risk of infection. Methods. Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs’ National Surgical Quality Improvement Program database. Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection. Results. Data on 24,774 patients were analyzed. Wound infection was present in 752 (3.04%) patients, 287 (1.16%) deep, and 468 (1.89%) superficial. Postoperative infection was associated with longer hospital stay (7.12 vs. 4.20 days), higher 30-day mortality (1.06% vs. 0.5%), higher complication rates (1.24% vs. 0.05%), and higher return to the operating room rates (37% vs. 2.45%). Multivariate logistic regression identified insulin dependent diabetes (odds ratios [OR] = 1.50), current smoking (OR = 1.19) ASA class of 3 (OR = 1.45) or 4 to 5 (OR = 1.66), weight loss (OR = 2.14), dependent functional status (1.36) preoperative HCT <36 (1.37), disseminated cancer (1.83), fusion (OR = 1.24) and an operative duration of 3 to 6 hours (OR = 1.33) or >6 hours (OR = 1.40) as statistically significant predictors of postoperative infection. Conclusion. Using multivariate analysis of a large prospectively collected data from the National Surgical Quality Improvement Program database, we identified the most important risk factors for increased postoperative spinal wound infection. We have demonstrated the high mortality, morbidity, and hospitalization costs associated with postoperative spinal wound infections. The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients.

Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease.

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimers disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons.

The Appropriate Use of Neurostimulation of the Spinal Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases: The Neuromodulation Appropriateness Consensus Committee

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.

Cervical spondylotic myelopathy: complications and outcomes after spinal fusion.

OBJECTIVE There is little information about in-hospital complication rates, adverse outcomes, and mortality after spinal fusion for cervical spondylotic myelopathy (CSM). The aim of this study was to report inpatient mortality, complications, and outcomes on a national level. METHODS We used the National Inpatient Sample to identify 58,115 admissions of patients with CSM who underwent spinal fusion in the United States from 1993 to 2002. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on outcomes such as mortality, complications, discharge disposition, and length of stay. RESULTS A total of 58,115 patients with CSM underwent spinal fusion with an average mortality rate of 0.6%, a complication rate of 13.4%, and a mean length of stay of 4 days. Pulmonary (3.6%) and postoperative hemorrhages or hematomas (2.3%) were the most common complications reported. One postoperative complication led to a 4-day increase in mean length of stay, increased the mortality rate 20-fold, and added more than

Visual Loss After Spine Surgery : A Population-Based Study

10,000 to hospital charges. Multivariate analysis identified age, comorbidity, and admission type as the main predictors of mortality, complication rate, and adverse outcome. Patients aged > or =85 or 65 to 84 years had respective 44- and 14-fold increases in mortality, compared with patients in the 18- to 44-year age group. Patients older than 84 years had a 40-fold increase in adverse outcomes and a 5-fold likelihood of medical complications. Patients with three or more comorbidities had an increased risk of medical complications (odds ratio [OR], 1.98), adverse discharge (OR, 2.17), and in-hospital mortality (OR, 2.36). Elective admissions were associated with much lower rates of mortality (OR, 0.28), complication (OR, 0.68), and adverse outcome (OR, 0.26). Complications were greater for posterior fusion (16.4%) versus anterior fusion (11.9%) procedures. Anterior fusions were associated with a greater incidence of dysphagia (3%) and hoarseness (0.21%). Cervical spondylosis patients who presented without myelopathy had a much lower incidence of complications (6.3%). CONCLUSIONS We provide a national estimate of inpatient complications and outcomes after spinal fusion for CSM patients in the United States. We demonstrate the impacts of age, complications, and medical comorbidities on the outcome of surgery for patients with this common disorder. We provide complication rates stratified by age and medical comorbidities for elderly patients who present with CSM who need spinal fusion.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases

Study Design. Retrospective cohort study using National inpatient sample administrative data. Objective. To determine national estimates of visual impairment and ischemic optic neuropathy after spine surgery. Summary of Background Data. Loss of vision after spine surgery is rare but has devastating complications that has gained increasing recognition in the recent literature. National population-based studies of visual complications after spine surgery are lacking. Methods. All patients from 1993 to 2002 who underwent spine surgery (Clinical Classifications software procedure code: 3, 158) and who had ischemic optic neuropathy (ION) (ICD9-CM code 377.41), central retinal artery occlusion (CRAO) (ICD9-CM code 362.31) or non-ION, non-CRAO perioperative visual impairment (ICD9-CM codes: 369, 368.4, 368.8–9368.11–13) were included. Univariate and multivariate analysis were performed to identify potential risk factors. Results. The overall incidence of visual disturbance after spine surgery was 0.094%. Spine surgery for scoliosis correction and posterior lumbar fusion had the highest rates of postoperative visual loss of 0.28% and 0.14% respectively. Pediatric patients (<18 years) were 5.8 times and elderly patients (>84 years) were 3.2 times more likely than, patients 18 to 44 years of age to develop non-ION, non-CRAO visual loss after spine surgery. Patients with peripheral vascular disease (OR = 2.0), hypertension (OR = 1.3), and those who received blood transfusion (OR = 2.2) were more likely to develop non-ION, non-CRAO vision loss after spine surgery. Ischemic optic neuropathy was present in 0.006% of patients. Hypotension (OR = 10.1), peripheral vascular disease (OR = 6.3) and anemia (OR = 5.9) were the strongest risk factors identified for the development of ION. Conclusion. We used multivariate analysis to identify significant risk factors for visual loss after spine surgery. National population-based estimate of visual impairment after spine surgery confirms that ophthalmic complications after spine surgery are rare. Since visual loss may be reversible in the early stages, awareness, evaluation and prompt management of this rare but potentially devastating complication is critical.

Effects of age and comorbidities on complication rates and adverse outcomes after lumbar laminectomy in elderly patients.

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.

National inpatient complications and outcomes after surgery for spinal metastasis from 1993–2002

Study Design. This is a retrospective cohort study using the National Inpatient Sample database. Objective. The objective is to report mortality and complications after lumbar laminectomy in the elderly. Summary of Background Data.— As the population continues to age in the United States, it is important to consider the surgical complications and outcomes in the elderly. A review of the literature reveals controversy over the safety of lumbar laminectomy in the elderly and disagreement over estimates of risks in this population. Methods. Outcome measures were abstracted from the National Inpatient Sample. Multivariate analysis was performed to analyze the effect of patient and hospital characteristics on outcome measures. Results. A total of 471,215 patients underwent lumbar laminectomy without fusion for lumbar stenosis from 1993 to 2002. The in-hospital mortality rate was 0.17%, and the complication rate was 12.17%. Postoperative hemorrhage or hematoma (5.2%) and nonspecific renal complications (2.8%) were the most common complications. Complication and mortality rates increased with age and comorbidities with an 18.9% complication rate and 1.4% mortality rate in patients over the age of 85 with 3 or more comorbidities, 14.7% complication rate and 0.22% mortality rate in patients over 85 with no comorbidities, and only a 6% complication rate and 0.05% mortality rate in patient between 18 and 44 with no comorbidities. Multivariate analysis revealed increased odds of mortality with increasing number of comorbidities and complications in the greater than 85 year age group. Increasing age, number of comorbidities, complication rate, and female sex also increased the odds of discharge to institution other than home. Conclusion. Elderly patients with comorbidities are at a higher risk for complications and adverse outcome after lumbar spine surgery. The effects of age and comorbidities on patient outcomes have been quantified. This information is critical in counseling elderly patients about the risk of surgery in their age group.

Craniotomy for resection of meningioma in the elderly: a multicentre, prospective analysis from the National Surgical Quality Improvement Program

Information regarding patient outcomes, complications, and mortality after surgery for spinal metastasis has previously been derived from single‐institution series. The aim of this study was to report inpatient mortality, complications, and outcomes on a national level.