4 Domain Sports PROM in Spanish: Cross-cultural adaptation in the Chilean population and reliability analysis. / 4 Domain Sports PROM en español: adaptación transcultural en la población chilena y análisis de confiabilidad.

BACKGROUND: Patient-Reported Outcome Measures (PROMs) are tools of increasing interest in the sports population. The purpose of this study was to perform the cross-cultural adaptation and reliability analysis of the 4 Domain Sports Patient-Reported Outcome Measure (4DSP) into Spanish. METHODS: A six-stage cross-cultural adaptation protocol was executed to obtain the Spanish version of the 4DSP (S-4DSP). Subsequently, the questionnaire was administered to a population of 108 postoperative athletes with ACL (Anterior Cruciate Ligament) injuries. The questionnaire was administered again after 30 days. Acceptability, floor and ceiling effects, internal consistency (Cronbach's alpha), and reproducibility (Intraclass Correlation) were evaluated. RESULTS: The S-4DSP was fully completed by 108 participants (mean age 34±10.75, 26% women), achieving 100% acceptability. No floor effect was detected. The statistical analysis yielded a global Cronbach's alpha for the questionnaire of 0.65, and domain-specific alphas of 0.88, 0.72, 0.27, and 0.68 for the first, second, third, and fourth domains, respectively. The Intraclass Correlation test reached a maximum of 0.94 and a minimum of 0.48 for the first and fifth questions, respectively. CONCLUSIONS: The S-4DSP is a reliable and useful tool for evaluating Spanish-speaking athletes after ACL reconstruction.

Luxación tibiofibular proximal diagnóstico y tratamiento / Proximal tibiofibular joint dislocation diagnosis and treatment

Resumen: Introducción: La luxación tibiofibular proximal (LTFP) es una lesión poco frecuente y no diagnosticada. De no ser tratada a tiempo, puede generar una sintomatología crónica de dolor e inestabilidad. La escasa evidencia disponible no entrega un protocolo de enfrentamiento ni consenso respecto a su manejo. Con el objetivo de asistir al enfrentamiento de esta lesión, se presenta una revisión de la literatura de una LTFP con reducción espontánea. Caso clínico: Hombre de 22 años consulta por dolor intenso en su rodilla derecha, posterior a caída en cuatrimoto. Al examen físico con aumento de volumen doloroso en cara lateral de la rodilla y pierna proximal, con movilidad completa y estable. Radiografías son informadas sin alteraciones. Se mantiene la sospecha clínica de LTFP, se continúa estudio con resonancia magnética (RM), la que es sugerente de LTFP. Dentro de las 24 horas de evolución, el paciente indica haber sentido un clank espontáneo en su rodilla afectada con cese completo de sintomatología. Se sigue al paciente por tres meses con RM de control, manteniendo una rodilla asintomática; examen físico y funcionalidad normal. Conclusión: El diagnóstico de las LTFP requiere un adecuado uso de imágenes. Su manejo consiste en una reducción cerrada de urgencia y de no lograrse, una reducción abierta, reparación y fijación interna. El pronóstico de las reducciones espontáneas es incierto, por lo que deben ser seguidas de forma seriada y en caso de recidiva, manejadas quirúrgicamente según el tiempo de evolución.

Abstract: Introduction: Proximal tibiofibular joint dislocations (PTFJD) are uncommon and underdiagnosed injuries. Urgent reduction is mandatory to avoid chronic disfunction. The scarcely available literature does not present a unified management guideline. An acute PTFJD case report with spontaneous reduction and a review of the literature is presented, aiming to assist the diagnosis and management of this pathology. Case report: A 22-years old male presented to the emergency department with high intensity right knee pain after falling in a four-wheel motorcycle. The physical exam revealed a prominent painful mass on the lateral aspect of his knee and proximal leg. His range of motion and knee stability were unremarkable. X-rays were informed negative for musculoskeletal injuries. According to a sustained suspicion of PTFJD, the study was continued with a magnetic resonance imaging (MRI), which suggested PTFJD. During the following 24 hours, the patient referred he was entirely asymptomatic after feeling a loud «clank¼. He has been followed for three months with MRI, and remains asymptomatic with full functions. Conclusion: PTFJD diagnosis requires appropriate images. Urgent close reduction is mandatory; if unsuccessful, open reduction, primary repair and internal fixation are indicated. The prognosis of spontaneous reduction remains uncertain and requires a serial clinical evaluation. In the case of recurrence, the appropriate surgical management is indicated according to the elapsed time from the injury.

[Proximal tibiofibular joint dislocation diagnosis and treatment]. / Luxación tibiofibular proximal diagnóstico y tratamiento.

INTRODUCTION: Proximal tibiofibular joint dislocations (PTFJD) are uncommon and underdiagnosed injuries. Urgent reduction is mandatory to avoid chronic disfunction. The scarcely available literature does not present a unified management guideline. An acute PTFJD case report with spontaneous reduction and a review of the literature is presented, aiming to assist the diagnosis and management of this pathology. CASE REPORT: A 22-years old male presented to the emergency department with high intensity right knee pain after falling in a four-wheel motorcycle. The physical exam revealed a prominent painful mass on the lateral aspect of his knee and proximal leg. His range of motion and knee stability were unremarkable. X-rays were informed negative for musculoskeletal injuries. According to a sustained suspicion of PTFJD, the study was continued with a magnetic resonance imaging (MRI), which suggested PTFJD. During the following 24 hours, the patient referred he was entirely asymptomatic after feeling a loud "clank". He has been followed for three months with MRI, and remains asymptomatic with full functions. CONCLUSION: PTFJD diagnosis requires appropriate images. Urgent close reduction is mandatory; if unsuccessful, open reduction, primary repair and internal fixation are indicated. The prognosis of spontaneous reduction remains uncertain and requires a serial clinical evaluation. In the case of recurrence, the appropriate surgical management is indicated according to the elapsed time from the injury.

INTRODUCCIÓN: La luxación tibiofibular proximal (LTFP) es una lesión poco frecuente y no diagnosticada. De no ser tratada a tiempo, puede generar una sintomatología crónica de dolor e inestabilidad. La escasa evidencia disponible no entrega un protocolo de enfrentamiento ni consenso respecto a su manejo. Con el objetivo de asistir al enfrentamiento de esta lesión, se presenta una revisión de la literatura de una LTFP con reducción espontánea. CASO CLÍNICO: Hombre de 22 años consulta por dolor intenso en su rodilla derecha, posterior a caída en cuatrimoto. Al examen físico con aumento de volumen doloroso en cara lateral de la rodilla y pierna proximal, con movilidad completa y estable. Radiografías son informadas sin alteraciones. Se mantiene la sospecha clínica de LTFP, se continúa estudio con resonancia magnética (RM), la que es sugerente de LTFP. Dentro de las 24 horas de evolución, el paciente indica haber sentido un clank espontáneo en su rodilla afectada con cese completo de sintomatología. Se sigue al paciente por tres meses con RM de control, manteniendo una rodilla asintomática; examen físico y funcionalidad normal. CONCLUSIÓN: El diagnóstico de las LTFP requiere un adecuado uso de imágenes. Su manejo consiste en una reducción cerrada de urgencia y de no lograrse, una reducción abierta, reparación y fijación interna. El pronóstico de las reducciones espontáneas es incierto, por lo que deben ser seguidas de forma seriada y en caso de recidiva, manejadas quirúrgicamente según el tiempo de evolución.

Cardiovagal and somatic sensory nerve functions in healthy subjects.

PURPOSE: Heart rate response to deep breathing (HRDB), which depends on the integrity of cardiac vagal preganglionic neurons and efferent fibers, and the function of sural nerve fibers are both associated with an age-related decline process. The aim of this study was to determine whether the effects attributed to aging on cardiovagal and sural nerve function decline are associated. METHODS: HRDB and sural sensory nerve action potential (SNAP) amplitude, latency, and conduction velocity (SCV) were measured in one hundred healthy asymptomatic subjects (aged 14-92 years, 41 women). Multiple and simple linear regressions were used to analyze the relationships between the variables. RESULTS: There were significant linear relationships between sural SNAP amplitude and HRDB with age. There was also a significant linear relationship between sural SNAP amplitude and HRDB (correlation coefficient 0.46, p<0.0001), but the model explained only 21.5 % of the variability in HRDB. CONCLUSION: Cardiovagal function assessed by HRDB is associated with sural SNAP amplitude in healthy subjects. Age-related decline only partially explained the variability seen in the association. Other genetic and environmental factors may also play a role.

Incidence of multiple sclerosis in Chile. A hospital registry study.

OBJECTIVE: To study the incidence of MS in Chile by examining the hospitalizations across all geographical regions of the country and to examine whether there is a correlation between these rates and the latitude or ultraviolet radiation. METHODS: This is a descriptive study examining the national registry of hospitalizations because of MS (code G35 in ICD-10) from January 1, 2001, to December 31, 2006. Incidence rates were calculated by gender and geographical region and standardized to the world population estimated for 2010. RESULTS: A total of 6857 hospitalizations were analyzed. There were 935 individuals; 63.9% were women. The mean incidence rate for 2002-2006 period was 0,90 (95% CI: 0.75-1.05). The annualized incidence rates for regions from North to South were as follows: I Tarapaca 0.54 (95% CI: 0.0-1.21), II Antofagasta 0,93 (0.10-1.75), III Atacama 1.07 (0.0-2.31), IV Coquimbo 0.63 (0.01-1.24), V Valparaiso 0.83 (0.38-1.27), VI O'Higgins 0.72 (0.14-1.30), VII Maule 0.52 (0.06-0.98), VIII BIO BIO 0.81 (0.41-1.21), IX Araucanía 0.43 (0.0-0.86), X Los Lagos 0.91 (0.35-1.46), XI Aysen 0.99 (0.0-2.98), XII Magallanes 3.54 (0.57-6.51), and XIII Metropolitana 1.10 (0.84-1.36). There were no significant correlations between hospitalization rates and latitude, except for region XII. UV radiation levels showed significant differences only for region XII. CONCLUSION: There is a moderate risk of MS in Chile. The southernmost region showed significantly higher incidence rates than those in the rest of the country (a cluster zone). We did not find any correlation between incidence rates and latitude or UV radiation.

Ubiquitin immunoreactivity in presumed spinal interneurones in motor neurone disease.

Previous studies have demonstrated the presence of ubiquitin-immunoreactivity (Ub-IR) as inclusions and skeins in motor neurones of both the familial and sporadic forms of motor neurone disease (MND). There is evidence that interneurones also degenerate in MND, but Ub-IR in ventral horn spinal interneurones has not been studied previously. Here, Ub-IR was investigated in 1445 presumed interneurones and 1086 presumed motor neurones counted in three random 20-microm sections of the ventral horn of the third lumbar segment of the spinal cord of each of seven controls and seven patients with MND. The ventral horn was divided into four quadrants; the dorsomedial quadrant contains almost exclusively interneurones and the ventrolateral quadrant largely motor neurones. The neurones were also classified by morphological and size criteria into presumed interneurones (< 25 microm) and presumed motor neurones (>or= 25 microm). Ub-IR was classified as inclusions, skeins and dispersed cytoplasmic and nuclear staining. Ub-IR inclusions or skeins were not observed in the controls but 6.6% of neurones (motor neurones and interneurones) showed the presence of dispersed cytoplasm staining and nuclear staining. The incidence of Ub-IR cytoplasmic and nuclear staining was significantly greater in both motor neurones and interneurones of MND patients than controls. Ub-IR was less frequent in MND cases in which a great loss of neurones was observed. Ub-IR was significantly more frequent in motor neurones than interneurones, both in patients and controls. Ub-IR inclusions and skeins were only observed in motor neurones from MND patients. Ub-IR inclusions were not observed in presumed spinal interneurones, while skeins were only seen in three out of 565 of these cells (two of them in the dorsomedial quadrant) in two out of seven patients. Thus, although presumed spinal interneurones occasionally revealed Ub-IR features similar to motor neurones, the rare staining of Ub-IR skeins and the lack of Ub-IR inclusions in interneurones in MND suggests that these neurones only occasionally form ubiquitin-protein conjugates. Neuronal size, rather than type, may be important in determining whether ubiquitin-protein conjugates form in the ventral horn neurones in MND.

Interneuronal survival and calbindin-D28k expression following motoneuron degeneration.

Degeneration of both motoneurons and interneurons has been previously observed in amyotrophic lateral sclerosis. It is unclear whether interneuronal loss is due to an intrinsic neuronal defect or if it occurs secondary to loss of their target motoneurons. We have examined the target dependence of interneurons, their survival and alterations in the expression of the calcium binding protein, calbindin-D28k (CB), in the ventral horn of the rat lumbar cord after extensive motoneuron degeneration was induced by unilateral rhizotomy of spinal nerves L2-L6 at postnatal day 3 (P3). Counts of Nissl-stained cells at P21 revealed no significant interneuronal death despite loss of 80% of their target motoneurons. At P6, some motoneurons transiently expressed CB on the operated side compared to the control side. Since most of these cells are destined to die, this transiently increased CB expression may represent an abortive attempt by the axotomised motoneurons to buffer the neurotoxic consequences of high intracellular calcium. In contrast, there was a time-dependent decrease in CB expression in ventral horn interneurons, with only 35% of putative Renshaw cells expressing CB by P21. These results indicate that neonatal interneurons are capable of surviving the loss of their motoneuron targets, but alter their phenotype as indicated by functional alterations in calcium-binding proteins.

A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group.

To test the safety and efficacy of recombinant human insulin-like growth factor-I (rhIGF-I) in ALS, 183 patients from eight European centers were randomized to receive double-blind placebo (n = 59) or rhIGF-I 0.1 mg/kg/day (n = 124) subcutaneously for 9 months. At study completion, the primary efficacy outcome measure (change in disease progression as assessed by the Appel ALS rating scale) showed no significant difference between treatment groups. RhIGF-I appeared to be safe and well-tolerated.

Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS.

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated myelin and oligodendrocyte injury, and simultaneous impairment of repair mechanisms due to a deficiency of S-adenosylmethionine (SAM). Products derived from macrophages may interfere directly with the methyl transfer cycle through the generation of reactive oxygen intermediates and reactions involving nitric oxide and peroxynitrite which may limit the supply of methionine for conversion to SAM, both by direct interaction as well as through inhibition of methionine synthase. Macrophage activation with secretion of cytokines and other biologically reactive substances within the nervous system is sustained in the late stages of HIV infection by the general effects of immune depletion, including loss of T cells (with concomitant reduction of macrophage regulatory molecules) and recurrent opportunistic infections, and may be further augmented by the local presence of the virus itself (or its surface glycoprotein gp120). This would account for the common, but not exclusive, occurrence of vacuolar myelopathy in AIDS. The ability of the virus and its products to stimulate macrophage and microglial activation may also explain the association between severity of vacuolar myelopathy and the presence of HIV encephalitis. A similar mechanism may underlie the pathogenesis of dementia, cerebral atrophy, and peripheral neuropathy. Local factors or differential susceptibility between the central and peripheral nervous system may determine whether myelinotoxic or neurotoxic processes predominate; the prominence of myelin involvement in the spinal cord, and axonal involvement peripherally may reflect both ends of this range, with the brain manifesting a more equal balance of both processes.

AIDS-associated vacuolar myelopathy and tumor necrosis factor-alpha (TNF alpha).

The spinal cords from 15 patients with AIDS-associated vacuolar myelopathy (VM), 4 AIDS patients without VM, and 5 HIV-seronegative controls, were studied with immunocytochemistry for TNF alpha. CSF and blood from HIV-seropositive patients with VM (n = 16), non-vacuolar myelopathies (n = 8), CNS infection but no clinical myelopathy (n = 31), no clinical or radiological evidence of CNS disease (n = 9), and from 7 HIV-seronegative controls with motor neurone disease were assayed for TNF alpha using an ELISA technique. TNF alpha was present on immunostaining in all the 15 cords with VM studied. The stained cells were macrophages, microglia and endothelial cells. The amount of immunostaining was higher in cords with VM compared with cords from HIV-seropositive patients without VM (p = 0.001). The distribution of staining corresponded to the areas of pathology but did not correlate with the severity of the VM. Immunostaining was also higher in the HIV-seropositive group compared to the HIV-seronegative controls (p = 0.001). There was no significant difference in the levels of TNF alpha in the CSF of patients with VM compared to any of the other groups studied. Blood levels of TNF alpha were lower in the HIV-seropositive controls without CNS disease and in the HIV-seronegative MND controls, than in patients with VM, non-vacuolar myelopathies, and CNS disease. CSF TNF alpha levels did not appear to be a reliable indicator of intramedullary levels. The findings support the hypothesis that TNF alpha may be relevant in the pathogenesis of vacuolar change in VM.

AIDS-associated vacuolar myelopathy. A morphometric study.

The post-mortem pathology in 20 spinal cords of human immunodeficiency virus (HIV) infected patients with vacuolar myelopathy was quantified by evaluating (i) the intensity of myelin change, vacuolation and macrophage density; and (ii) the areas of white matter covered by each feature. Severity scores were constructed for (i) the anterior, lateral, and posterior white matter columns; (ii) each level of spinal cord; and (iii) the whole spinal cord [Cord Total and Cord Average Severity Scores (CTSS, CASS)]. Astroglial activation was scored separately. In 14 cords with mild-moderate vacuolar myelopathy (CASS = 23-259), macrophages were the most prominent pathological feature, and level severity scores were higher at mid-thoracic than cervical levels (P = 0.009). In six cords with severe vacuolar myelopathy (CASS = 396-614), vacuolation, demyelination and macrophages were equally evident and thoracic and cervical level severity scores were similar. The most severe lesions showed evidence of clearing of macrophages from the collapsed centres. A clinical lower limb score correlated with the anterior (P = 0.03) and lateral (P = 0.04) column total scores and with the CTSS (P = 0.04) in the nine patients who had had both myelopathy related disability and all cord levels available. There was no significant longitudinal gradient in score severity in the posterior, lateral or anterior columns and no evidence of a dying-back phenomenon. There was no evidence of Wallerian degeneration occurring as a primary process. Astroglial activation did not correlate with the severity or duration of the vacuolar myelopathy. Detection of HIV p24 antigen in the spinal cord related to the local presence of multinucleated giant cells and to antigen expression in the brain but not with the severity of vacuolar myelopathy. The pathology in vacuolar myelopathy appeared to start in the mid-low thoracic cord, with increasing rostral involvement as the disease became more severe. The relative prominence of macrophages in mild-moderate lesions suggests they may be involved early in the pathogenesis of vacuolar myelopathy.

Continuous response variable trial design in motor neuron disease: long term treatment with a TRH analogue (RX77368).

The continuous response variable controlled trial design is developed as a model for the efficient screening of candidate treatments in motor neuron disease. A TRH analogue (RX77368) and placebo were randomly allocated to 15 matched pairs of patients with motor neuron disease. With validated composite interval scores, this trial excluded a 50% or greater improvement with RX77368 at month 12 in scores of respiratory, lower limb, and activities of daily living function with greater than 90% power, and in bulbar function scores with 80% power. For upper limbs, 52% and 75% improvements were excluded at months 9 and 12 respectively with 80% power. Patients who died during the study had faster deterioration rates in bulbar and respiratory scores than their surviving pairs. The feasibility of screening drugs for significant biological effects with small sample sizes and good statistical power is shown. The difficulties of handling deaths and dropouts when using this design are discussed. Comparisons are made with sample sizes required using other scores and rating scales, as well as with those required in hazard and event rate studies. A simple clinical grading scale for motor neuron disease, with its corresponding composite interval scores, is described.

Natural history of amyotrophic lateral sclerosis. Observations with the Charing Cross Amyotrophic Lateral Sclerosis Rating Scales.

Natural history data increase the descriptive knowledge about amyotrophic lateral sclerosis (ALS), help define primary outcome variables and numbers of patients needed on clinical trials, and may give valuable predictive information. Global scores do not adequately represent the clinical variability of ALS. The Charing Cross Quantitative and Qualitative ALS Rating Scales assess disease severity and progression by validated regional scores (bulbar, respiration, upper limb, lower limb) and activities of daily living. The main stages in the development of these scales are summarized. Interval, or quantitative, scales provide accurate and sensitive measurements of the evolution of the disease and are useful for phase II therapeutic trials. The deterioration rates of regional scores in individual patients may not be linear. Rates of disease progression in ALS vary (1) among patients, (2) among topographical regions within a single patient, and (3) at different stages of the disease in a single region in the same patient. The deterioration rates of the regional scores of an ALS population depend critically on whether deaths are included or excluded from the population mean scores. Qualitative scales with simple scores are best suited for large-scale, phase III trials and for life table analysis of times to failure.

Accuracy, reproducibility and variability of quantitative assessments of bulbar and respiratory function in motor neurone disease.

The validity of quantitative tests to assess bulbar and respiratory function used in therapeutic trials in motor neurone disease (MND) is studied in 26 MND and 21 age- and sex-matched control subjects. Five raters timed repeated visual and auditory stimuli generated by a metronome simulating bulbar tests. For all raters, mean error rate was 5.07%, correlation coefficient was 0.89 (and %difference of 1.53), and coefficient of variation (CV) was 3.18%. The experienced rater obtained significantly better %differences and CV. For all subjects and tests, mean correlation coefficient was 0.98, and mean CV was 8.8%. There were no significant differences in reproducibility or variability in readings obtained in MND and control subjects assessed by the experienced rater. The use of composite bulbar, but not respiratory, scores resulted in significant improvements in reproducibility and variability.

Accuracy, reproducibility, and variability of hand-held dynamometry in motor neuron disease.

A spring-loaded device that "breaks" at preset forces was used to assess readings obtained by hand-held dynamometry by three raters with varying experience in the method. Overall accuracy (3%), but not reproducibility or variability, was improved by greater experience. Readings obtained jointly by three raters had 53% greater variability than those obtained by a single rater. Nine muscle groups in 19 patients with motor neuron disease were assessed at 10 sessions (three replications per session) over six days by the experienced rater. Muscle force was expressed relative to that of 22 matched normal controls. The reproducibility was good with a mean % difference of 13.2 and repeatability coefficient of 2.17 kg-force for readings six days apart; the overall correlation coefficient was 0.98. The mean coefficient of variation (CV) of 10 readings was 9.9%. The poorer reproducibility and greater variability seen in clinically weaker muscles may account for differences in patients with bulbar palsy and classical amyotrophic lateral sclerosis; the degree of spasticity had no effect. The rater was estimated to contribute 37% of the total variability when testing patients. The use of a composite score by combining normalised dynamometry readings of eight limb muscles improved mean % difference to 6.7 and mean CV to 5.8%. The reproducibility and variability of hand-held dynamometry readings obtained by a single rater compare well with those of fixed devices. Readings from single raters, irrespective of experience, have similar reproducibility and variability. If, however, multiple raters are used in longitudinal assessments of individual patients, as occurs in clinical trials, the variability of their combined readings should be estimated when calculating the same size required.

Motor neurone disease.

Motor neurone disease, or amyotrophic lateral sclerosis, is a serious progressive neurological disorder, characterized by loss of UMN and LMN. Pathological features include characteristic intracytoplasmic MN inclusion bodies and appearances on ubiquitin staining. The aetiopathogenesis of the disease remains unknown and there is, to date, no effective treatment. Several abnormalities have been demonstrated in neurotransmitter, neuropeptide and gene expression studies. Abnormalities in glutamate metabolism have led to the excitotoxin hypothesis of MN destruction. Other theories include deficits in MN trophic factors, trans-synaptic degeneration, impaired ability to detoxify putative toxic agents and impaired DNA/RNA metabolism. The existence of familial forms, some of which show linkage to markers in chromosome 21, allows a genetic approach to the mechanisms of disease. Recent studies suggest that mutations in the Cu/Zn SOD gene may be important in some of the familial forms. The atypical forms seen in the Western Pacific have stimulated a search for environmental agents. Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue.