RESUMEN
Infectious mononucleosis may mimic lymphoma, both clinically and histopathologically. We present a patient with neurological symptoms and lymphadenopathy, initially diagnosed as Epstein-Barr virus (EBV)-positive angioimmunoblastic T-cell lymphoma (AITL) with cerebrospinal fluid (CSF) localisation based on lymph node pathology and a 30-fold higher EBV load in the CSF compared with serum. However, the patient fully recovered spontaneously and EBV became negative in both CSF and serum, suggestive of a dramatic presentation of EBV meningoencephalitis.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Meningoencefalitis/diagnóstico , Meningoencefalitis/virología , Líquido Cefalorraquídeo/virología , Diagnóstico Diferencial , Humanos , Linfoma/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control. PATIENTS AND METHODS: At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate-severe) pain. Differences were tested with the χ(2) test. RESULTS: During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001). CONCLUSION: Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain. CLINICAL TRIAL NUMBER: Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324).
Asunto(s)
Neoplasias/fisiopatología , Manejo del Dolor , Dolor/fisiopatología , Toma de Decisiones Asistida por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Pacientes Ambulatorios , Dolor/complicaciones , Dolor/tratamiento farmacológico , Dimensión del Dolor/métodos , Médicos , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Peripheral neuropathy is a frequent side effect of bortezomib chemotherapy. Relatively little is known about the clinical characteristics of this neuropathy, especially with respect to pain. Our aim was to describe the clinical characteristics and course of bortezomib-induced polyneuropathy. METHODS: This is a retrospective cohort study of 39 patients diagnosed with bortezomib-induced polyneuropathy. RESULTS: Pain is the most prominent symptom and 14 of 39 patients suffered from severe pain. More than 50% of our patients used analgesics due to moderate or severe pain. We found no correlation between severity of symptoms of bortezomib-induced polyneuropathy and cumulative dose or dose intensity of bortezomib. Nerve conduction studies did not correlate well with symptom severity. Dose reduction or discontinuation of treatment reduced severity in most cases. CONCLUSION: Painful polyneuropathy is a frequent, dose-limiting side effect of bortezomib with a relatively good prognosis. Careful neurological monitoring of symptoms and timely dose adjustment is important.
Asunto(s)
Ácidos Borónicos , Bortezomib , Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Estudios de Cohortes , Humanos , Mieloma Múltiple , Polineuropatías , Pirazinas/uso terapéutico , Estudios RetrospectivosRESUMEN
Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide and newer agents such as bortezomib. The incidence and degree of neuropathy depends on the type of cytotoxic drug, the duration of administration, cumulative dose and pre-existing peripheral neuropathy. Because of increasing survival rates of patients treated with neurotoxic agents, CIPN is accompanied by a significant decrease in the patient's quality of life among cancer survivors. Therefore, several neuroprotective strategies, including calcium/magnesium infusion, amifostine, gluthatione, glutamine, acetyl-L-carnitine and erythropoietin as most promising, have been investigated to decrease the neurotoxicity without compromising anti-tumour efficacy. However, clinical evidence for the efficacy of these drugs is sparse. In this review we will give an outline of the neurotoxic effects of chemotherapeutic agents, their clinical manifestations and potential neuroprotective strategies.
Asunto(s)
Antineoplásicos/efectos adversos , Fármacos Neuroprotectores/uso terapéutico , Síndromes de Neurotoxicidad/etiología , Humanos , Magnesio/uso terapéutico , Síndromes de Neurotoxicidad/tratamiento farmacológico , Protectores contra Radiación/uso terapéutico , Factores de Riesgo , Vitamina E/uso terapéuticoRESUMEN
Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.
Asunto(s)
Mieloma Múltiple/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ácidos Borónicos/efectos adversos , Bortezomib , Diagnóstico Precoz , Humanos , Factores Inmunológicos/efectos adversos , Incidencia , Mieloma Múltiple/complicaciones , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/epidemiología , Inhibidores de Proteasoma , Pirazinas/efectos adversos , Talidomida/efectos adversosRESUMEN
There is increasing evidence that pain transmission on one side of the body is influenced by a painful state on the other side. We have investigated this phenomenon by studying the activation pattern (using C-fos labeling) of spinal glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the ipsilateral hind paw of rats that were preconditioned with an acute or chronic pain stimulus in the contralateral hind paw or rats that were not preconditioned (control). For this purpose, fluorescent in situ hybridization with GlyT2 and GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. Rats were preconditioned with acute (capsaicin, Complete Freund's Adjuvant (CFA) 1.5 h), chronic inflammatory (CFA 20 h and 4 days), neuropathic (spared nerve injury (SNI) 2 weeks), or control pain stimuli (saline 20 h and 4 days; sham-SNI 2 weeks). We found that after capsaicin injection in rats preconditioned with CFA inflammation (4 days), sham-SNI or with SNI neuropathic pain, the numbers (27 ± 3, 21 ± 2, and 21 ± 2, respectively) and percentages (55% ± 4, 43% ± 2, and 42% ± 2, respectively) of C-fos activated neurons that were Gly/GABA increased significantly as compared with control (10 ± 1 and 25% ± 2). The increase in the total number of C-fos activated Gly/GABA neurons was present primarily in the superficial dorsal horn (laminae I and II; control: 9%; CFA 4 days: 56%; SNI 2 weeks: 42%). This increase in C-fos activation of Gly/GABA neurons occurred without significant changes in the total number of C-fos activated neurons, and without any significant changes in the mechanical thresholds in the hind paws after capsaicin injection. The results showed that one-sided chronic pain, especially inflammation, significantly increases the C-fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal cord. This further underlines the existence of a dynamic interaction between ipsi- and contralateral spinal neurons in the processing of nociceptive information.
Asunto(s)
Capsaicina/farmacología , Lateralidad Funcional/fisiología , Neuronas GABAérgicas/fisiología , Glicina/fisiología , Neuralgia/fisiopatología , Neuronas/fisiología , Médula Espinal/fisiología , Animales , Adyuvante de Freund/farmacología , Inflamación/inducido químicamente , Inflamación/fisiopatología , Masculino , Imagen Molecular/métodos , Dolor/inducido químicamente , Dolor/fisiopatología , Umbral del Dolor/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismoRESUMEN
BACKGROUND: Pain in Guillain-Barré syndrome (GBS) may be pronounced and is often overlooked. OBJECTIVES: To obtain detailed information about pain in GBS and its clinical variants. METHODS: This was a prospective cohort study in 156 patients with GBS (including 18 patients with Miller Fisher syndrome [MFS]). We assessed the location, type, and intensity of pain using questionnaires at standard time points during a 1-year follow-up. Pain data were compared to other clinical features and serology. RESULTS: Pain was reported in the 2 weeks preceding weakness in 36% of patients, 66% reported pain in the acute phase (first 3 weeks after inclusion), and 38% reported pain after 1 year. In the majority of patients, the intensity of pain was moderate to severe. Longitudinal analysis showed high mean pain intensity scores during the entire follow-up. Pain occurred in the whole spectrum of GBS. The mean pain intensity was predominantly high in patients with GBS (non-MFS), patients with sensory disturbances, and severely affected patients. Only during later stages of disease, severity of weakness and disability were significantly correlated with intensity of pain. CONCLUSIONS: Pain is a common and often severe symptom in the whole spectrum of GBS (including MFS, mildly affected, and pure motor patients). As it frequently occurs as the first symptom, but may even last for at least 1 year, pain in GBS requires full attention. It is likely that sensory nerve fiber involvement results in more severe pain.
Asunto(s)
Síndrome de Guillain-Barré/complicaciones , Dolor/etiología , Potenciales de Acción/fisiología , Adulto , Anticuerpos/sangre , Distribución de Chi-Cuadrado , Estudios de Cohortes , Evaluación de la Discapacidad , Electromiografía/métodos , Fatiga/etiología , Fatiga/fisiopatología , Femenino , Gangliósidos/inmunología , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Dolor/inmunología , Dimensión del Dolor/métodos , Tiempo de Reacción/fisiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadística como Asunto , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are potent trophic factors for dorsal root ganglion cells. In addition, these factors are produced in subsets of dorsal root ganglion cells and transported anterogradely to their terminals in the superficial dorsal horn of the spinal cord, where they constitute the only source of GDNF and BDNF. We investigated the effect of 10 mug GDNF and BDNF injected by lumbar puncture on the expression of the immediate early gene (IEG) products c-Fos, c-Jun, and Krox-24 in the adult rat dorsal horn. In the dorsal horn of S1 spinal segments, GDNF and BDNF induced a strong increase in IEG expression, which was most pronounced in laminae I and II (2.9- to 4.5-fold). More distal from the injection site, in the dorsal horn of L1/L2 spinal segments, the increase in IEG expression was less pronounced, suggesting a concentration-dependent effect. In order to explain the effects of intrathecally injected GDNF, we investigated whether lumbo-sacral dorsal horn neurons expressed RET protein, the signal-transducing element of the receptor complex for GDNF. It was found that several of these neurons contained RET immunoreactivity and that some of the RET-labeled neurons had the appearance of nociceptive-specific cells, confirming their presumed role in pain transmission. Additionally, using double-labeling immunofluorescence combined with confocal microscopy, it was found that after intrathecal GDNF injection 35% of c-Fos-labeled cells were also labeled for RET. These results demonstrate that intrathecally administered GDNF and BDNF induce IEG expression in dorsal horn neurons in the adult rat, supposedly by way of their cognate receptors, which are present on these neurons. We further suggest that the endogenous release of GDNF and BDNF, triggered by nociceptive stimuli, is involved in the induction of changes in spinal nociceptive transmission as in various pain states.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Genes Inmediatos-Precoces/fisiología , Factores de Crecimiento Nervioso/farmacología , Fármacos Neuroprotectores/farmacología , Células del Asta Posterior/fisiología , Animales , Genes Inmediatos-Precoces/efectos de los fármacos , Factor Neurotrófico Derivado de la Línea Celular Glial , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , Inmunohistoquímica , Inyecciones Espinales , Masculino , Células del Asta Posterior/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Proto-Oncogénicas c-ret , Ratas , Ratas Wistar , Proteínas Tirosina Quinasas Receptoras/metabolismo , Transmisión Sináptica/fisiologíaRESUMEN
Glial cell line-derived neurotrophic factor (GDNF) is produced in a subset of adult rat spinal ganglion neurons and anterogradely transported to the superficial dorsal horn. In this study the effect of sciatic nerve axotomy on the expression of GDNF protein in the dorsal horn was investigated, using immunocytochemistry. Image analysis showed a 44% decrease relative to the non-transected side after 5 days survival, progressing to more than 80% decrease after 10 days and remaining so for at least 100 days. This rapid and strong decrease suggests active down-regulation of GDNF protein after peripheral axotomy. The observed down-regulation of GDNF is compared with changes observed for other substances in primary afferents after peripheral axotomy and is discussed in light of its presumed trophic or transmitter role in nociception.
Asunto(s)
Factores de Crecimiento Nervioso/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas Aferentes/metabolismo , Médula Espinal/metabolismo , Animales , Axotomía , Supervivencia Celular/fisiología , Factor Neurotrófico Derivado de la Línea Celular Glial , Inmunohistoquímica , Masculino , Fibras Nerviosas/fisiología , Ratas , Ratas Wistar , Médula Espinal/citologíaRESUMEN
Immunocytochemistry was used to identify glial cell line-derived neurotrophic factor (GDNF) in rat spinal cord. Strong GDNF labeling was found in fibers and terminals in laminae I and II (outer) and to a lesser extent in the remaining laminae. A few spinal ganglion cells also contained GDNF. After dorsal root transection GDNF disappeared from the dorsal horn and after dorsal root ligation there was accumulation of GDNF only on the ganglion side of the ligation. These findings demonstrate anterograde transport of GDNF within primary afferent fibers, which constitute the only source of GDNF labeling in the dorsal horn. The strong presence of GDNF in the superficial dorsal horn may indicate that GDNF has a role in pain transmission in the adult rat spinal cord.
Asunto(s)
Factores de Crecimiento Nervioso/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas Aferentes/metabolismo , Médula Espinal/citología , Médula Espinal/metabolismo , Animales , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial , Inmunohistoquímica , Masculino , Fibras Nerviosas/metabolismo , Ratas , Ratas WistarRESUMEN
The objective of this open, retrospective study was to investigate whether intravenous immunoglobulin (IVIg) could induce a clinically obvious improvement in patients with generalized myasthenia gravis (MG), as judged by MG functional status. Fourteen patients with generalized MG were treated during at least one episode with 0.4 g IVIg per kilogram body weight per day for 5 consecutive days. Patients with confounding variables were excluded; this left 11 patients (16 episodes) to be further analysed. We defined improvement as at least a one-step improvement in MG functional status (according to the University of Virginia's Modification of Osserman's classification). Of the treatment episodes, 56% were classified as positive responses. If improvement occurred, onset of improvement started after 3 (1-12) days and peak effect was reached after 7 (4-30) days (median and range). All four patients who required artificial ventilation could be weaned from it 8.5 (6-11) days after the start of IVIg (median and range). Of the patients treated on two occasions, only one patient had a positive response during both. In MG functional status 5, improvement was observed during five of seven episodes. None of the patients with MG functional status 3 responded. Patients with an acute relapse of MG seemed to respond equally well to IVIg compared with patients with subacute deterioration/ chronic-static state (50% versus 60%). The MG functional status at the start of IVIg and on the day of maximal improvement was compared for all episodes together, and significant improvement was noted (P = 0.0052). We did not see any serious side-effects after IVIg treatment. This retrospective analysis suggests that high-dose IVIg is an effective therapy in some patients with deterioration of generalized MG. If improvement occurs, it starts within a few days of the onset of IVIg and the effect seems to peak within 2 weeks.