Aging with spinal cord injury: A narrative review of consequences and challenges.

Given the increase in life expectancy, aging with a pre-existing spinal cord injury (SCI) is becoming more common. This condition is challenging as compromised health status and functional independence can worsen. We aimed to provide an updated overview of the consequences of aging with SCI, highlighting the main challenges facing this population in a narrative review of the current literature we retrieved from the PubMed database from 2000 to 2022 on any aspect related to aging in persons with SCI. Here we address adverse circumstances that increase disability and hinder an active lifestyle, such as progressive physical deterioration, secondary health conditions, limitations in personal activity, changes in family and social support structures, aging of caregivers, and depletion of economic resources. Favorable changes are also observed, including psychosocial adjustments that improve quality of life. Additionally, various interventions are discussed to promote well-being, health, and social participation. Due to the relevance of this issue, people with SCI and all those who take care of them must have up-to-date information to carry out the necessary measures to promote healthy aging in a more inclusive social environment.

Functional improvement in individuals with chronic spinal cord injury treated with 4-aminopyridine: A systematic review.

Study design: Systematic review. Objective: To provide current evidence on the efficacy of 4-aminopyridine (4-AP) to bring about functional improvement in individuals with chronic traumatic spinal cord injury (SCI). Methods: The Medline (PubMed), Web of Science and SCOPUS databases were systematically searched for relevant articles on the efficacy of 4-AP to treat SCI, from the dates such articles were first published until May 2022. Full-text versions of all the articles selected were examined independently by two reviewers. Methodological quality was rated using the Modified Jadad Scale, and risk of bias was assessed with the RoB-2 test. Data extracted included human models/types, PRISMA assessment protocols, and the results of each study. Descriptive syntheses are provided. Results: In total, 28 articles were initially identified, 10 of which were included after screening. Most of the studies reviewed reported some degree of patient improvement in one or more of the following parameters: motor, sensitivity and sexual function, sphincter control, spasticity, ability to function independently, quality of life, central motor conduction, pain, and pulmonary function. Conclusions: This review confirms the efficacy of 4-AP in improving several conditions resulting from SCI but further research on this topic is warranted. Additional randomized clinical trials with 4-AP involving larger sample sizes are needed, as are consistent outcome measures in order to obtain adequate data for analysis with a view to enhance treatment benefits. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=334835, PROSPERO CRD42022334835.

Evolution of Spinal Cord Transection of Rhesus Monkey Implanted with Polymer Synthesized by Plasma Evaluated by Diffusion Tensor Imaging.

In spinal cord injury (SCI) there is damage to the nervous tissue, due to the initial damage and pathophysiological processes that are triggered subsequently. There is no effective therapeutic strategy for motor functional recovery derived from the injury. Several studies have demonstrated neurons growth in cell cultures on polymers synthesized by plasma derived from pyrrole, and the increased recovery of motor function in rats by implanting the polymer in acute states of the SCI in contusion and transection models. In the process of transferring these advances towards humans it is recommended to test in mayor species, such as nonhuman primates, prioritizing the use of non-invasive techniques to evaluate the injury progression with the applied treatments. This work shows the ability of diffusion tensor imaging (DTI) to evaluate the evolution of the SCI in nonhuman primates through the fraction of anisotropy (FA) analysis and the diffusion tensor tractography (DTT) calculus. The injury progression was analysed up to 3 months after the injury day by FA and DTT. The FA recovery and the DTT re-stabilization were observed in the experimental implanted subject with the polymer, in contrast with the non-implanted subject. The parameters derived from DTI are concordant with the histology and the motor functional behaviour.

Zika and dengue but not chikungunya are associated with Guillain-Barré syndrome in Mexico: A case-control study.

Background Zika, dengue and chikungunya viruses (ZIKV, CHIKV and DENV) are temporally associated with neurological diseases, such as Guillain-Barré syndrome (GBS). Because these three arboviruses coexist in Mexico, the frequency and severity of GBS could theoretically increase. This study aims to determine the association between these arboviruses and GBS in a Mexican population and to establish the clinical characteristics of the patients, including the severity of the infection. A case-control study was conducted (2016/07/01-2018/06/30) in Instituto Mexicano del Seguro Social (Mexican Social Security Institute) hospitals, using serum and urine samples that were collected to determine exposure to ZIKV, DENV, CHIKV by RT-qPCR and serology (IgM). For the categorical variables analysis, Pearson's χ2 or Fisher exact tests were used, and the Mann-Whitney U test for continuous variables. To determine the association of GBS and viral infection diagnosis through laboratory and symptomatology before admission, we calculated the odds ratio (OR) and 95% confidence intervals (95%CI) using a 2x2 contingency table. A p-value ≤ 0.05 was considered as significant. Ninety-seven GBS cases and 184 controls were included. The association of GBS with ZIKV acute infection (OR, 8.04; 95% CI, 0.89-73.01, p = 0.047), as well as laboratory evidence of ZIKV infection (OR, 16.45; 95% CI, 2.03-133.56; p = 0.001) or Flavivirus (ZIKV and DENV) infection (OR, 6.35; 95% CI, 1.99-20.28; p = 0.001) was observed. Cases of GBS associated with ZIKV demonstrated a greater impairment of functional status and a higher percentage of mechanical ventilation. According to laboratory results, an association between ZIKV or ZIKV and DENV infection in patients with GBS was found. Cases of GBS associated with ZIKV exhibited a more severe clinical picture. Cases with co-infection were not found.

Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury.

The regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated peripheral nerve (PPN) grafts or the use of bone marrow stromal cells (BMSCs) or exogenous molecules, such as chondroitinase ABC (ChABC) promote axonal growth and remyelination, resulting in an improvement in locomotor function. These treatments have been primarily assessed in acute injury models. The aim of the present study is to evaluate the ability of several single and combined treatments in order to modify the course of chronic complete SCI in rats. A complete cord transection was performed at the T9 level. One month later, animals were divided into five groups: original injury only (control group), and original injury plus spinal cord re-transection to create a gap to accommodate BMSCs, PPN, PPN + BMSCs, and PPN + BMSCs + ChABC. In comparison with control and single-treatment groups (PPN and BMSCs), combined treatment groups (PPN + BMSCs and PPN + BMSCs + ChABC) showed significative axonal regrowth, as revealed by an increase in GAP-43 and MAP-1B expression in axonal fibers, which correlated with an improvement in locomotor function. In conclusion, the combined therapies tested here improve locomotor function by enhancing axonal regeneration in rats with chronic SCI. Further studies are warranted to refine this promising line of research for clinical purposes.

Zika Virus infection and Guillain-Barré syndrome in Northeastern Mexico: A case-control study.

BACKGROUND: Beginning August 2017, we conducted a prospective case-control investigation in Monterrey, Mexico to assess the association between Zika virus (ZIKV) and Guillain-Barré syndrome (GBS). METHODS: For each of 50 GBS case-patients, we enrolled 2-3 afebrile controls (141 controls in total) matched by sex, age group, and presentation to same hospital within 7 days. RESULTS: PCR results for ZIKV in blood and/or urine were available on all subjects; serum ZIKV IgM antibody for 52% of case-patients and 80% of controls. Subjects were asked about antecedent illness in the two months prior to neurological onset (for case-patients) or interview (for controls). Laboratory evidence of ZIKV infection alone (PCR+ or IgM+) was not significantly different between case-patients and controls (OR: 1.26, 95% CI: 0.45-3.54) but antecedent symptomatic ZIKV infection [a typical ZIKV symptom (rash, joint pain, or conjunctivitis) plus laboratory evidence of ZIKV infection] was higher among case-patients (OR: 12.45, 95% CI: 1.45-106.64). GBS case-patients with laboratory evidence of ZIKV infection were significantly more likely to have had typical ZIKV symptoms than controls with laboratory evidence of ZIKV infection (OR: 17.5, 95% CI: 3.2-96.6). This association remained significant even when only GBS case-patients who were afebrile for 5 days before onset were included in the analysis, (OR 9.57 (95% CI: 1.07 to 85.35). CONCLUSIONS: During ZIKV epidemics, this study indicates that increases in GBS will occur primarily among those with antecedent symptomatic ZIKV.

Evaluación semicuantitativa de gliomas cerebrales en adultos: un enfoque de las características neuropatológicas.

INTRODUCTION: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. OBJECTIVE: To develop a semi-quantitative scale to numerically grade gliomas morphological characteristics. METHOD: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. RESULTS: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). CONCLUSIONS: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

INTRODUCCIÓN: Los gliomas son neoplasias con alta recurrencia y mortalidad. Por la dificultad para aplicar la clasificación de la Organización Mundial de la Salud (2016), los países en desarrollo siguen utilizando la evaluación histológica para diagnosticarlos y clasificarlos. OBJETIVO: Desarrollar una escala semicuantitativa para calificar numéricamente las características morfológicas de los gliomas. MÉTODO: Cohorte de pacientes con gliomas evaluada y seguida durante 36 meses. Se analizaron y calificaron cortes del tejido tumoral, incluyendo aspectos como estirpe celular, celularidad, pleomorfismo nuclear, mitosis, hiperplasia endotelial, cambios hipóxicos, cuerpos apoptóticos, necrosis, hemorragia e índice de proliferación. RESULTADOS: Se analizaron 58 casos. La mediana de la calificación de los gliomas de bajo grado fue de 12 puntos (percentiles 25 y 75 de 9 y 13.5, respectivamente) y la de los gliomas de alto grado fue de 17 puntos (percentiles 25 y 75 de 16 y 20.5, ­respectivamente) (p < 0.0001). La supervivencia a 36 meses de los pacientes con gliomas de bajo (13/17) y alto grado (6/41) también fue significativamente diferente (p < 0.0001). CONCLUSIONES: La escala morfológica semicuantitativa permite una evaluación objetiva de los gliomas, con una adecuada correlación entre la calificación, el grado del tumor y el tiempo de supervivencia.

Semi-quantitative evaluation of brain gliomas in adults: A focus on neuropathological characteristics

Introduction: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. Objective: To develop a semi-quantitative scale to numerically grade gliomas by its morphological characteristics. Method: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. Results: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). Conclusions: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

Semi-quantitative evaluation of brain gliomas in adults: A focus on neuropathological characteristics.

INTRODUCTION: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. OBJECTIVE: To develop a semi-quantitative scale to numerically grade gliomas by its morphological characteristics. METHOD: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. RESULTS: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). CONCLUSIONS: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

Oxidative stress in the elderly with diabetes mellitus or hypertension / Estrés oxidativo en adultos mayores con diabetes mellitus o hipertensión arterial

Background: Mexico City has the highest aging rate in the country, as well as a high prevalence of diabetes mellitus (DM) and hypertension (HT). It is known that each one of these conditions increase oxidative stress (OS) independently. Methods: With this study we described changes in OS of 18 patients without DM or HT (controls), 12 with DM, 23 with HT, and 18 with DM and HT, all of them members of the COSFAMM (Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México). OS was measured by the quantification of reactive oxygen species (ROS), by the oxidation of diclorofluorosceine, and by determination of lipid peroxidation by product malondialdehyde (MDA). Results: HT patients showed increased ROS levels, as did men with HT compared with the respective DM and HT groups. Also, women of control group showed higher levels of ROS compared with men. Conclusions: Generally, HT turned out to be the most influential factor for the increase of oxidative stress in the elderly while DM has no effect whatsoever.

Introducción: la Ciudad de México tiene el mayor índice de envejecimiento del país, así como una alta prevalencia de diabetes mellitus (DM) e hipertensión arterial (HTA). Se sabe que cada una de estas condiciones incrementa el estrés oxidativo (EO) de forma independiente. Métodos: en este estudio describimos los cambios en el EO de 18 pacientes sin DM ni HTA (controles), 12 con DM, 23 con HTA y 18 con DM y HTA, todos miembros de la Cohorte de Obesidad, Sarcopenia y Fragilidad en Adultos Mayores de México (COSFAMM). El EO fue medido por la cuantificación de especies reactivas de oxígeno (ERO) por la oxidación de la diclorofluorosceína (DCFH) y por determinación de peroxidación de lípidos por producto malondialdehído (MDA). Resultados: los pacientes con HTA mostraron niveles de ERO elevados, así como los hombres con HTA, comparados con los grupos correspondientes de DM y HTA. Asimismo, las mujeres del grupo control mostraron mayor cantidad de ERO que los hombres. Conclusiones: en general, la HTA en el adulto mayor resultó ser el factor que mayor contribución tiene en el incremento del estrés oxidativo, mientras que la DM no tiene efecto alguno.

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials.

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 µL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

BACKGROUND: Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. METHOD: The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. RESULTS: The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. CONCLUSION: The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs.

The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection.

Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model.

Genetic polymorphisms associated with antiepileptic metabolism.

Several factors, including pharmacogenetics, contribute to inter-individual variability in drug response. Many antiepileptic drugs (AEDs) are metabolized by a variety of enzymatic reactions, and the cytochrome P450 (CYP) family has attracted considerable attention. Some of the CYPs exist as genetic (allelic) variants, which may also affect the plasma concentrations or drug exposure. Regarding the metabolism of AEDs, the polymorphic CYP2C9 and CYP2C19 are of particular interest. There have been recent advances in discovering factors such as these, especially those underlying the risk of medication toxicity. This review summarizes the evidence about whether such polymorphisms affect the clinical action of AEDs to facilitate future studies on the pharmacogenetics of epilepsy. We performed Key Words searches in the public databases PubMed, Medscape, and Rxlisty, Pharm GKB for genetic polymorphisms and the NCBI website for the nomenclature of alleles of CYP450, finding that CYP2D6, CYP2C9, CYP3A4, and CYP2D19 were involved in the metabolism of most antiepileptic drugs, given the allele frequency in the population and the associated variability in the clinical response.

Value of EQ-5D in Mexican city older population with and without dementia (SADEM study).

BACKGROUND: The EuroQoL-5D (EQ-5D) is a brief, multi-attribute, preference-based health status measurement. The objective of this study was to assess the validity and reliability of EQ-5D in older adults with and without dementia in Mexico City. METHODS: The Study on Aging and Dementia in Mexico (SADEM) was a survey of 3101, Mexican adults (60 + years old). An in-home face-to-face interview was administered. EQ-5D using ranking to rate states on a 100-point visual analogue scale; Daily Living Activities (ADL), Instrumental Activities of Daily Living (IADL), Mini Mental State Examination (MMSE), Short Form of the quality of life survey (SF-36), and Charlson comorbility index were used for comparison. The validity and reliability of EQ-5D were tested. We identified states of health for direct valuation; state 11111 ("no problems") had to be included because it was essential to the reseating (onto a 0-1 scale) of the visual analogue scale data. We included all plausible combinations of levels across each of the five EQ-5D dimensions and evaluated any significant interaction effects and factorial designs, based on balanced complete blocks. RESULTS: The EQ-5D was applied to 3101 older people, of whom 109 (3.4%) had dementia. The general reliability of EQ-5D for cases was 0.80 and for controls 0.76, for each dimension. We had a total of 103 combinations for controls and 45 for cases. The percentage for the state of health "no problems" (11111) for controls was 30.4%, and had the highest percentage of cases (8.8%). CONCLUSION: The resulting valuations form the basis for clinical use and facilitate the interpretation and evaluation of health care.

Human papillomavirus genotypes among females in Mexico: a study from the Mexican institute for social security.

BACKGROUND: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Spatial and temporal morphological changes in the subarachnoid space after graded spinal cord contusion in the rat.

Spontaneous repair or treatment-induced recovery after spinal cord injury (SCI) is very limited and might be related to extramedullary alterations that have only briefly been documented. Here we report on the morphological changes of the spinal subarachnoid space (SAS) in a clinically relevant model of SCI. Anesthetized rats were subjected either to mild or severe spinal cord contusion at T9. Spine blocks from the site of injury and adjacent segments were harvested at acute (1 h and 1 day [d]), subacute (3 and 7 d), and chronic (1 and 3 months) stages post-injury. Histopathology and morphometry at each decalcified vertebral level were assessed. At acute and subacute stages, reduction of SAS lumen was observed after both mild and severe injuries. Acutely, after severe injuries, SAS occlusion was associated mainly with cord swelling and subarachnoid hematomas; a trend for dural sac constriction was observed for mild injuries. At 7 d, cord swelling diminished in both instances, but dural sac constriction increased for severe injuries. At early stages, in the epicenter and vicinity, histopathology revealed compression of neurovascular elements within the SAS, which was more intense in severe than in mild injuries. In the chronic stage, SAS lumen increased notably, mostly from cord atrophy, despite dural sac constriction. Myelograms complemented observations made on SAS lumen permeability. Post-traumatic arachnoiditis occurred mainly in animals with severe injury. In conclusion, early extramedullary SAS changes described here might be expected to produce alterations in cerebrospinal fluid (CSF) dynamics and cord blood perfusion, thereby contributing to the pathophysiology of SCI and becoming novel targets for treatment.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

BACKGROUND: Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. METHODS: Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. RESULTS: Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. CONCLUSIONS: Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.

High doses of 4-aminopyridine improve functionality in chronic complete spinal cord injury patients with MRI evidence of cord continuity.

BACKGROUND AND AIMS: Many patients with complete spinal cord injury (SCI) exhibit demyelinated and poorly myelinated nerve fibers traversing the lesion site. Conventional doses of 4-aminopyridine (4-AP, 30 mg/day) have shown to provide no or minor functional improvement in these patients. We undertook this study to test the functional effect of high doses of 4-AP on patients with chronic complete SCI with cord continuity at the site of injury demonstrated by magnetic resonance imaging. METHODS: Fourteen patients were included in a double-blind, randomized, placebo-controlled trial followed by an open label long-term follow-up. Initially, patients received 4-AP or placebo orally, with 4-AP being increased gradually (5 mg/week) to reach 30 mg/day. For long-term treatment, 4-AP was increased 10 mg periodically according to negative electroencephalogram and blood test abnormalities and minor adverse reactions. Pre-treatment, 12 and 24 weeks of the controlled trial, and 6 and 12 months of open trial evaluations, or with the highest doses reached were obtained. RESULTS: Three of 12 patients were able to walk with the assistance of orthopedic devices, 1/12 became incomplete (AIS B), 7/12 improved their somatosensory evoked potentials, 5/12 had sensation and control of bladder and anal sphincters, and 4/9 male patients had psychogenic erection. CONCLUSIONS: Positive changes were seen mainly in patients with cyst (4/5) or atrophy (3/5) of the injury site. Two patients withdrew from the study: one had seizures and one had intolerant adverse reactions. We conclude that high doses of 4-AP in the studied population produced several functional benefits not observed using lower doses.

Stereolithography in spine pathology: a 2-case report.

BACKGROUND: Solid plastic replicas of anatomical structures obtained by stereolithography from computed tomographic images and magnetic resonance imaging are being used as complementary tools for diagnostic purposes and therapy planning for diverse pathologies. CASE DESCRIPTIONS: Case 1--The spine mold of a 62-year-old man with neurologic compromise secondary to degenerative cervical disease was used to study the pathologic features of his spine and to plan and simulate the approach to remove osteophytes before surgery. Also, by examining the replica of his spine, the unconvinced patient was able to understand the nature of his pathology and realize that his neurologic symptoms would disappear only through surgery, as they did. Case 2--A 27-year-old woman had uncontrolled back and leg pain possibly related to anxiety and depression. She had undergone one unsuccessful lumbo-sacral surgery and was now obsessed with the thought that her second surgery, performed by us, likewise had failed, even though her magnetic resonance images proved otherwise. It was not until she held a replica of her repaired spine in her hands that she was able to understand that her pain was unfounded. Once she was able to relax, her chronic pain and anxiety disappeared within a month, using the same antidepressive treatment that formerly had been ineffective. CONCLUSIONS: Spine replicas are useful devices for diagnosis, planning, and simulating surgery, and they enable patients to understand the nature of their pathologies and the surgical procedures at hand.