Efecto del tratamiento con denosumab durante 24 meses en individuos con lesión medular reciente con osteoporosis / Effect of 24-month denosumab treatment in individuals with recent spinal cord injury and osteoporosis

Introducción: El desarrollo de osteoporosis es una complicación frecuente tras una lesión medular (LM), especialmente bajo el nivel de la lesión. Sin embargo, su abordaje terapéutico continúa siendo incierto.Objetivo: Analizar la evolución de la densidad mineral ósea (DMO) y de los marcadores de remodelado óseo (MRO) en individuos con una LM reciente y osteoporosis asociada tratados con denosumab durante 24 meses.Métodos: Estudio prospectivo en el que se incluyeron pacientes con LM reciente y osteoporosis que recibieron tratamiento con denosumab durante 24 meses. A todos ellos se les realizó una analítica con determinación de MRO (PINP, CTX y FA ósea), 25-OH- vitamina D y una densitometría ósea en columna lumbar y fémur proximal basal y a los 12 y 24 meses.Resultados: Se incluyeron 13 pacientes (media de edad de 39±15 años) con LM reciente (con un tiempo medio de evolución de 15 meses) y osteoporosis. Todos los pacientes recibieron tratamiento con denosumab durante 24 meses. A los 12 meses de tratamiento con denosumab se observó un aumento significativo de la DMO en columna lumbar y fémur proximal, con un incremento adicional de los valores de DMO tras 24 meses de tratamiento, que fue del orden del 9,1% en columna lumbar, 4,4% en cuello de fémur y 5,3% en fémur total. Asimismo, los valores de los MRO disminuyeron de forma significativa durante los 24 meses de tratamiento. Ningún paciente presentó fracturas por fragilidad y no se observaron acontecimientos adversos relacionados con el tratamiento.Conclusiones: El tratamiento con denosumab durante 24 meses aumenta la DMO lumbar y femoral y disminuye los MRO en pacientes con LM reciente con osteoporosis. Denosumab parece ser una opción terapéutica prometedora en esta condición clínica. (AU)

Describing post-polio syndrome.

INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.

Describiendo el síndrome pospolio / Describing post-polio syndrome

Introducción: Las personas con secuelas de poliomielitis pueden presentar nuevos síntomas que constituirían el síndrome pospolio (SPP). Objetivo Identificar el perfil clínico y funcional, y las características epidemiológicas de personas que padecen SPP. Pacientes y métodos: Estudio retrospectivo de 400 pacientes afectados de poliomielitis visitados en consulta externa del Institut Guttmann, de los cuales a 310 se les diagnosticó SPP. Se describieron variables epidemiológicas, clínicas y electromiográficas. Se analizó la relación entre edad de adquisición de la polio y gravedad de la misma, así como entre el sexo y la edad de aparición del SPP y la frecuencia de síntomas. Resultados: Se observó mayor frecuencia de SPP en mujeres (57,7%). La edad media de inicio de la clínica fue 52,4 años, más precoz en mujeres. Edad de primoinfección mayor de 2 años no se relacionó con mayor gravedad de la polio. La frecuencia de síntomas fue: dolor 85%, pérdida de fuerza 40%, fatiga 65,5%, cansancio 57,8%, intolerancia al frío 20,2%, disfagia 11,7%, quejas cognitivas 9%, síntomas depresivos 31,5%. La fatiga, el cansancio, la depresión y las quejas cognitivas fueron significativamente más frecuentes en mujeres. El 59% de los pacientes presentaban hallazgos electromiográficos sugestivos de SPP. Conclusiones: El tipo de sintomatología que presentaba nuestra muestra es similar a la publicada, no así en la frecuencia de la misma. Creemos que el perfil clínico de los pacientes podría ser muy diverso, y dar mayor peso a parámetros objetivos como el empeoramiento o la aparición de debilidad y el estudio de biomarcadores podría acercarnos más a un diagnóstico preciso. (AU)

Introduction: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). Objective: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. Patients and methods: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients’ epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. Results: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. Conclusions: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients’ clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis. (AU)

Describing post-polio syndrome. / Describiendo el síndrome pospolio.

INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection >2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.

Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA.

Marked trabecular and cortical bone loss was observed at the proximal femur short-term after spinal cord injury (SCI). 3D-DXA provided measurement of vBMD evolution at both femoral compartments and cortical thinning, thereby suggesting that this technique could be useful for bone analysis in these patients. INTRODUCTION: SCI is associated with a marked increase in bone loss and risk of osteoporosis development short-term after injury. 3D-DXA is a new imaging analysis technique providing 3D analysis of the cortical and trabecular bone from DXA scans. The aim of this study was to assess the evolution of trabecular macrostructure and cortical bone using 3D-DXA in patients with recent SCI followed over 12 months. METHODS: Sixteen males with recent SCI (< 3 months since injury) and without antiosteoporotic treatment were included. Clinical assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD [vBMD] and cortical thickness) were performed at baseline and at 6 and 12 months of follow-up. RESULTS: vBMD significantly decreased at integral, trabecular, and cortical compartments at 6 months (- 8.8, - 11.6, and - 2.4%), with a further decrease at 12 months, resulting in an overall decrease of - 16.6, - 21.9, and - 5.0%, respectively. Cortical thickness also decreased at 6 and 12 months (- 8.0 and - 11.4%), with the maximal decrease being observed during the first 6 months. The mean BMD losses by DXA at femoral neck and total femur were - 17.7 and - 21.1%, at 12 months, respectively. CONCLUSIONS: Marked trabecular and cortical bone loss was observed at the proximal femur short-term after SCI. 3D-DXA measured vBMD evolution at both femoral compartments and cortical thinning, providing better knowledge of their differential contributory role to bone strength and probably of the effect of therapy in these patients.

Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy.

There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis. INTRODUCTION: Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators. METHODS: Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group. RESULTS: At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes. CONCLUSIONS: RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.

Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury.

UNLABELLED: Osteoporosis is a frequent complication related to spinal cord injury (SCI), and data on osteoporosis treatment after SCI is scarce. Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis. INTRODUCTION: Osteoporosis development is a frequent complication related to SCI, especially at the sublesional level. Nevertheless, data on osteoporosis treatment after SCI is scarce, particularly short term after injury, when the highest bone loss is produced. The aim of this study was to analyze the efficacy of denosumab in the treatment of SCI-related osteoporosis. METHODS: Fourteen individuals aged 39 ± 15 years with osteoporosis secondary to recent SCI (mean injury duration 15 ± 4 months) were treated with denosumab for 12 months. Bone turnover markers (BTMs) (PINP, bone ALP, sCTx), 25-hydroxyvitamin D (25OHD) levels and bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were assessed at baseline and at 12 months. All participants received calcium and vitamin D supplementation. RESULTS: At 12 months, SCI denosumab-treated participants showed a significant increase in BMD at TH (+2.4 ± 3.6 %, p = 0.042), FN (+3 ± 3.6 %, p = 0.006), and LS (+7.8 ± 3.7 %, p < 0.001) compared to baseline values. Denosumab treatment was associated with significant decreases in BTMs (bone ALP -42 %, p < 0.001; PINP -58 %, p < 0.001, sCTx -57 %, p = 0.002) at 12 months. BMD evolution was not related to BTM changes or 25OHD serum levels. No skeletal fractures or serious adverse events were observed during follow-up. CONCLUSIONS: Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis.

Síndrome post-polio, quejas cognitivas y exploración neuropsicológica / Postpolio syndrome, subjective cognitive complaints and neuropsychological assessment

Objetivo: Estudiar el rendimiento psicométrico de una muestra de pacientes afectados por el síndrome post-polio que manifiestan quejas cognitivas. Pacientes y método: La muestra estaba formada por 37 pacientes (17 hombres) con síndrome post-polio atendidos en consulta externa de Neuropsicología. La edad media en el momento de la exploración neuropsicológica era de 55 años (DE: 4,58 años). El 59,5% recibía tratamiento farmacológico por la presencia de sintomatología ansioso-depresiva. Los resultados obtenidos por los pacientes en la exploración neuropsicológica fueron comparados con los baremos normativos a fin de identificar el porcentaje de pacientes con puntuaciones patológicas para cada uno de los test aplicados. Resultados: Los pacientes presentaban puntuaciones patológicas en todos los test neuropsicológicos; siendo especialmente relevante el porcentaje de puntuaciones indicativas de alteración cognitiva en los test que valoraban velocidad de procesamiento cognitivo, aprendizaje verbal, fluencia verbal fonémica y flexibilidad cognitiva. No se observaron diferencias estadísticamente significativas en el rendimiento de los pacientes en función de la presencia o ausencia de sintomatología ansioso-depresiva. Conclusiones: Los pacientes afectados de síndrome post-polio que manifiestan quejas cognitivas presentan un rendimiento psicométrico inferior al de la población general (AU)

Objective: To examine psychometric performance in a sample of patients with postpolio syndrome (PPS) with subjective cognitive complaints. Patients and methods: The sample consisted of 37 PPS patients (17 men) referred to our outpatient neuropsychological service. The mean age at the neuropsychological assessment was 55 years (SD: 4.58 years). A total of 59.5% was receiving pharmacological treatment for anxiety-depression. The results obtained by patients in the neuropsychological assessment were compared with normative data to identify the percentage of patients with pathological scores on the tests applied. Results: Patients with PPS had pathological scores on all the neuropsychological tests. A particularly significant finding was the percentage of patients with scores indicative of cognitive impairment in tests that assessed cognitive processing speed, verbal learning, phonemic verbal fluency and cognitive flexibility. No statistically significant differences were observed in patients’ performance depending on the presence or absence of anxiety or depression. Conclusions: Patients with PPS and subjective cognitive complaints performed less well on neuropsychological assessment than the general population (AU)

Risk factors for the development of osteoporosis after spinal cord injury. A 12-month follow-up study.

UNLABELLED: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis. The evaluation of bone mineral density shortly after SCI is a simple and effective method for predicting the development of osteoporosis during the first year after SCI. INTRODUCTION: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis and fractures. The aim of this study was to analyze the factors associated with osteoporosis development short-term after SCI. METHODS: We included patients with complete recent SCI (<6 months) evaluating bone turnover markers (P1NP, bone ALP, and sCTx), 25-OH-vitamin D (25OHD) levels, and lumbar and femoral BMD (Lunar, Prodigy) at baseline, 6 and 12 months after SCI. The risk factors for osteoporosis analyzed included the following: age, gender, BMI, toxic habits, bone turnover markers, 25OHD levels, lumbar and femoral BMD, level, severity and type of SCI, and days-since-injury. Osteoporosis was defined according to WHO criteria. RESULTS: Thirty-five patients aged 35 ± 16 years were included, and 52 % developed osteoporosis during the 12-month follow-up. These latter patients had lower BMD values at femur and lumbar spine and higher bone turnover markers at baseline. On multivariate analysis, the principal factors related to osteoporosis development were as follows: total femur BMD <1 g/cm(2) (RR, 3.61; 95 % CI 1.30-10.06, p = 0.002) and lumbar BMD <1.2 g/cm(2) at baseline (0.97 probability of osteoporosis with both parameters under these values). Increased risk for osteoporosis was also associated with increased baseline values of bone ALP (>14 ng/mL) (RR 2.40; 95 % CI 1.10-5.23, p = 0.041) and P1NP (>140 ng/mL) (RR 3.08; 95 % CI 1.10-8.57, p = 0.017). CONCLUSIONS: The evaluation of BMD at the lumbar spine and femur short-term after SCI is a simple, effective method for predicting the development of osteoporosis during the first year after SCI. Our results also indicate the need to evaluate and treat these patients shortly after injury.

Effect of intrathecal baclofen on evoked pain perception: an evoked potentials and quantitative thermal testing study.

BACKGROUND AND OBJECTIVES: Somatic antinociceptive effects of baclofen have been demonstrated in animal models. We hypothesized that if enhanced thermal or pain sensitivity is produced by loss of gamma-aminobutyric acid (GABA)-ergic tone in the central nervous system, spinal administration of GABA agonists might be predicted to be effective in thermal and/or pain perception changes and pain-related evoked potentials in candidates for intrathecal baclofen (ITB) treatment. METHODS: Eleven patients with severe spinal cord injury (SCI) who suffered from severe spasticity were evaluated during a 50-µg ITB bolus test. Warm and heat pain thresholds, evoked heat pain perception, and contact heat-evoked potentials (CHEPs) were determined above SCI level from the right and left sides. Nine age- and gender-matched healthy volunteers undergoing repeat testing without any placebo injection served as control group. RESULT: In patients, heat pain perception threshold increased, and evoked pain perception and amplitude of CHEPs decreased significantly after ITB bolus application in comparison with baseline (p < 0.005), with no change in warm perception threshold. In controls, no significant changes were observed in repeat testing over time. CONCLUSION: Our findings indicate that ITB modulates heat pain perception threshold, evoked heat pain perception and heat pain-related evoked potentials without inducing warm perception threshold changes in SCI patients. This phenomenon should be taken into account in the clinical evaluation and management of pain in patients receiving baclofen.

Cerebral hemorrhage due to autonomic dysreflexia in a spinal cord injury patient.

STUDY DESIGN: Case report. OBJECTIVE: To report an uncommon case of cerebral hemorrhage due to autonomic dysreflexia (AD) in a spinal cord injury (SCI) patient. SETTING: Institut Guttmann, Neurorehabilitation Hospital in Barcelona, Spain. CASE REPORT: An SCI patient developed AD due to urinary tract infection after surgery for a pressure sore. The hypertension was difficult to control and the case progressed to hypertensive encephalopathy. MRI of the brain was performed showing a hemorrhagic lesion on the left occipital area. The hypertension was finally controlled and the neurological status improved although with some cognitive deficits. CONCLUSION: This is an uncommon case of cerebral hemorrhage due to AD, showing the importance of an adequate diagnosis and treatment of AD to avoid this life-threatening complication.

Efficacy of intrathecal morphine in the treatment of baclofen tolerance in a patient on intrathecal baclofen therapy (ITB).

STUDY DESIGN: Case report. OBJECTIVES: A case report of tolerance to intrathecal baclofen therapy (ITB) treated with intrathecal morphine ('baclofen holiday'). SETTING: Institut Guttmann, Neurorehabilitation Hospital of Barcelona, Spain. CASE REPORT: A 30-year-old female patient is described with incomplete paraplegia below T6 on the left side and below T8 on the right side, ASIA B, caused by trauma occurring 12 years previously, in whom an intrathecal system had been implanted for baclofen infusion 10 years ago. The patient showed tolerance to baclofen therapy and was treated with intrathecal morphine infusion for 2 weeks. Baclofen infusion resulted in adequate control of spasticity.