RESUMO
Since the initial publication of Tsubokawa in 1991, epidural motor cortex stimulation (MCS) is increasingly reported as an effective surgical option for the treatment of refractory neuropathic pain although its mechanism of action remains poorly understood. The authors review the extensive literature published over the last 15 years on central and neuropathic pain. Optimal patient selection remains difficult and the value of pharmacological tests or transcranial magnetic stimulation in predicting the efficacy of MCS has not been established. Pre-operative functional magnetic resonance imaging (fMRI), 3-dimensional volume MRI, neuronavigation and intra-operative neurophysiological monitoring have contributed to improvements in the technique for identifying the precise location of the targeted motor cortical area and the correct placement of the electrode array. MCS should be considered as the treatment of choice in post-stroke pain, thalamic pain or facial anesthesia dolorosa. In brachial plexus avulsion pain, it is preferable to propose initially dorsal root entry zone (DREZ)-tomy; MCS may be offered after DREZotomy has failed to control the pain. In our experience, the results of MCS on phantom limb pain are promising. In general, the efficacy of MCS depends on: a) the accurate placement of the stimulation electrode over the appropriate area of the motor cortex, and b) on sophisticated programming of the stimulation parameters. A better understanding of the MCS mechanism of action will probably make it possible to adjust better the stimulation parameters. The conclusions of multicentered randomised studies, now in progress, will be very useful and are likely to promote further research and clinical applications in this field.
Assuntos
Terapia por Estimulação Elétrica , Córtex Motor/fisiopatologia , Neuralgia/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Monitorização Intraoperatória , Córtex Motor/efeitos da radiação , Neuralgia/patologia , Neuralgia/fisiopatologia , Neuronavegação/métodos , Estudos Retrospectivos , Literatura de Revisão como AssuntoRESUMO
Implantation of adrenal medullary bovine chromaffin cells (BCC), which synthesize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides, has been proposed for the treatment of intractable cancer pain. Macro- or microencapsulation of such cells within semipermeable membranes is expected to protect the transplant from the host's immune system. In the present study, we report the viability and functionality of BCC encapsulated into microcapsules of alginate-poly-L-lysine (PLL) with a liquefied inner core. The experiment was carried out during 44 days. Empty microcapsules were characterized in terms of morphology, permeability, and mechanical resistance. At the same time, the viability and functionality of both encapsulated and nonencapsulated BCC were evaluated in vitro. We obtained viable BCC with excellent functionality: immunocytochemical analysis revealed robust survival of chromaffin cells 30 days after isolation and microencapsulation. HPLC assay showed that encapsulated BCC released catecholamines basally during the time course study. Taken together, these results demonstrate that viable BCC can be successfully encapsulated into alginate-PLL microcapsules with a liquefied inner core.
Assuntos
Alginatos , Materiais Biocompatíveis , Transplante de Células/métodos , Células Cromafins/transplante , Polilisina/análogos & derivados , Animais , Western Blotting , Cápsulas , Catecolaminas/metabolismo , Bovinos , Sobrevivência Celular/fisiologia , Células Cultivadas , Células Cromafins/metabolismo , Células Cromafins/ultraestrutura , Cromatografia Líquida de Alta Pressão , Imuno-Histoquímica , Implantes Experimentais , Microscopia Confocal , Microscopia Eletrônica de Varredura , Neoplasias/complicações , Manejo da Dor , Permeabilidade , Fatores de TempoRESUMO
Chromaffin cells from the adrenal gland secrete a combination of neuroactive compounds including catecholamines, opioid peptides, and growth factors that have strong analgesic effects, especially when administered intrathecally. Preclinical studies of intrathecal implantation with xenogeneic bovine chromaffin cells in rats have provided conflicting data with regard to analgesic effects, and recent concern over risk of prion transmission has precluded their use in human clinical trials. We previously developed a new, safer source of adult adrenal chromaffin cells of porcine origin and demonstrated an in vivo antinociceptive effect in the formalin test, a rodent model of tonic pain. The goal of the present study was to confirm porcine chromaffin cell analgesic effects at the molecular level by evaluating neural activity as reflected by spinal cord c-Fos protein expression. To this end, the expression of c-Fos in response to intraplantar formalin injection was evaluated in animals following intrathecal grafting of 10(6) porcine or bovine chromaffin cells. For the two species, adrenal chromaffin cells significantly reduced the tonic phases of the formalin response. Similarly, c-Fos-like immunoreactive neurons were markedly reduced in the dorsal horns of animals that had received injections of xenogeneic chromaffin cells. This reduction was observed in both the superficial (I-II) and deep (V-VI) lamina of the dorsal horn. The present study demonstrates that both xenogeneic porcine and bovine chromaffin cells transplanted into the spinal subarachnoid space of the rat can suppress formalin-evoked c-Fos expression equally, in parallel with suppression of nociceptive behaviors in the tonic phase of the test. These findings confirm previous reports that adrenal chromaffin cells may produce antinociception by inhibiting activation of nociceptive neurons in the spinal dorsal horn. Taken together these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.
Assuntos
Células Cromafins/metabolismo , Fixadores/toxicidade , Formaldeído/toxicidade , Dor/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Medula Espinal/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Bovinos , Células Cromafins/transplante , Masculino , Dor/induzido quimicamente , Manejo da Dor , Medição da Dor/métodos , Células do Corno Posterior/metabolismo , Ratos , Ratos Sprague-Dawley , Transplante HeterólogoRESUMO
The objectives of this study were to compare the pharmacokinetic properties and the duration of analgesia following intrathecal administration (L5-S1) of 2 mg morphine in 2 forms: (1) an isobaric (NaCl 0.9%) and (2) a hyperbaric solution (7% dextrose). The study was carried out on 5 cancer patients with severe, intractable pain in the lower half of the body. Samples of CSF were collected at the level of the 10th thoracic vertebra at regular intervals for 15 h after administration. Morphine concentrations were determined by HPLC. The pharmacokinetic properties of the solutions (I and II) were quite different. Peak levels (I) were reached in 5-15 min (30 and 60 micrograms/ml); they then fell rapidly during the 1st hour (7 and 11 micrograms/ml) with an elimination half-life of 10 and 15 min, followed by a change in slope (elimination half-life of 108 and 140 min). Peak levels (II) were reached in 4-5 h (0.8-3.3 micrograms/ml); they then fell progressively according to a single exponential function (elimination half-life: 144-246 min). The duration of analgesia for a dose of 2 mg was 30 h for solution 2 and 24 h for solution 1. The hyperbaric solution, which produced the same degree of analgesia as the isobaric solution, limited the cephalad diffusion of morphine and reduced or abolished the central depressant effects of the drug.
Assuntos
Morfina/líquido cefalorraquidiano , Neoplasias/fisiopatologia , Dor Intratável/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Injeções Espinhais , Vértebras Lombares , Masculino , Morfina/administração & dosagem , Morfina/farmacocinética , Morfina/uso terapêutico , Dor Intratável/fisiopatologia , Soluções , Gravidade EspecíficaRESUMO
The control of chronic pain through transplantation of chromaffin cells has been reported over the past few years. Analgesic effects are principally due to the production of opioid peptides and catecholamines by chromaffin cells. Clinical trials have been reported with allografts consisting of whole-tissue fragments implanted into the subarachnoid space of the lumbar spinal cord (14,19,36). In the present study, allogeneic grafts were successfully used to control chronic pain in two patients over a period of 1 yr based on patient reported pain scores, morphine intake, and CSF levels of Met-enkephalin. Macroscopic examination at autopsy located the transplanted tissue fragments in the form of multilobulated nodules at the level of the spinal axis and cauda equina. Immunocytochemical microscopy showed neuroendocrine cells are positive for chromagranin A (CGA), and enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbetaH). The results suggest that there is a relationship between analgesic effect, Met-enkephalin levels in CSF, and the presence of chromaffin cells surviving in spinal subarachnoid space.
Assuntos
Células Cromafins/transplante , Sobrevivência de Enxerto , Neoplasias/complicações , Dor/cirurgia , Adulto , Doença Crônica , Encefalina Metionina/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Dor/etiologiaRESUMO
Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.
Assuntos
Medula Suprarrenal/citologia , Linfócitos T CD4-Positivos/citologia , Movimento Celular/imunologia , Células Cromafins/transplante , Sobrevivência de Enxerto/imunologia , Medula Suprarrenal/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/líquido cefalorraquidiano , Analgésicos Opioides/farmacocinética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/imunologia , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/imunologia , Encefalina Metionina/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Injeções Espinhais , Interferon gama/líquido cefalorraquidiano , Interleucina-10/líquido cefalorraquidiano , Interleucina-2/líquido cefalorraquidiano , Interleucina-6/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Morfina/líquido cefalorraquidiano , Morfina/farmacocinética , Fator de Crescimento Transformador beta/líquido cefalorraquidianoRESUMO
Transplantation of adrenal medullary tissue for terminal cancer pain has been tested clinically, but this approach is not practical for routine use because of the shortage of organ donors and lack of tissue homogeneity. As a first alternative step, we have generated immortalized chromaffin cells over-expressing opioid peptides, namely met-enkephalin. Rat chromaffin cells have been genetically modified with vectors containing expression cassettes with either synthetic met-enkephalin or pro-enkephalin gene coding regions, fused with the nerve growth factor signal peptide for secretion. After stable transfection and differentiation in vitro, met-enkephalin and pro-enkephalin cells had higher met-enkephalin immunoreactivity and secreted met-enkephalin levels, compared to control cells containing the expression vector only. In the formalin hindpaw-injection model, 15 days after subarachnoid transplant of cells, grafts of met-enkephalin and pro-enkephalin cells significantly reduced the number of formalin-evoked c-fos immunoreactive spinal neurons in the spinal cord, compared to grafts of vector-alone chromaffin cells. The use of such expandable cell lines, for chronic spinal delivery of opiates, could offer an attractive and safe alternative strategy based on ex vivo gene therapy for the control of opioid-sensitive chronic pain.
Assuntos
Células Cromafins/transplante , Encefalina Metionina/metabolismo , Formaldeído/farmacologia , Dor/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Medula Espinal/metabolismo , Análise de Variância , Animais , Contagem de Células/métodos , Linhagem Celular Transformada , Células Cromafins/metabolismo , Células Cromafins/fisiologia , Encefalina Metionina/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Engenharia Genética , Sobrevivência de Enxerto/fisiologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Dor/induzido quimicamente , Feniletanolamina N-Metiltransferase/metabolismo , RNA Mensageiro/biossíntese , Radioimunoensaio/métodos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Medula Espinal/efeitos dos fármacos , Transfecção/métodosRESUMO
The authors present seven cases of spinal trauma at the T-12--L-1 level with severe spinal canal stenosis secondary to compressive, anterior discocorporeal lesions. Associated neurological disorders were of varying severity. Six cases were investigated by computed tomography, which enabled the degree of thoracolumbar spinal canal stenosis to be determined. In all cases, the surgical procedure involved rectification of spinal deformity, with an initial unilateral posterolateral approach permitting anterior spinal canal recalibration, either by impaction of protrusive fragments or ablation of ejected disc fragments. The stabilization was in all cases achieved by complimentary bilateral plates using Roy-Camille material, associated with posterolateral arthrodesis by grafting with reconstruction of the articulopedicular structure. The functional spinal result was excellent in all cases, and recalibration was verified by tomography. In those cases showing neurological deficiency, good and early recovery was attributable to the suppression of spinal canal stenosis. The application of this posterolateral approach for severe lesions of the thoracolumbar junction seems to represent, in all cases of recent lesions, an alternative to the anterior or combined methods, which present widely recognized difficulties at the thoracoabdominal junction.
Assuntos
Canal Medular/cirurgia , Traumatismos da Coluna Vertebral/cirurgia , Adulto , Estudos de Avaliação como Assunto , Feminino , Humanos , Região Lombossacral , Masculino , Canal Medular/diagnóstico por imagem , Traumatismos da Coluna Vertebral/complicações , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/etiologia , Tórax , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: In our multidisciplinary pain clinic, three patients with amputated limbs and with surgical indications for chronic motor cortex stimulation for phantom limb pain were selected for their ability to voluntarily move the missing limb. The sensation of being able to move a missing limb at will occurs quite frequently among traumatic amputees, but the ability to control it sufficiently to perform a functional magnetic resonance imaging (fMRI) examination is more rarely encountered. We used motor fMRI to study these virtual movements. METHODS: In two patients with upper-limb amputations, movements of the stump, the normal hand, and the missing arm were studied. In a third patient with both legs amputated, movements of the stumps and of the missing feet were studied. The fMRI data were analyzed with the Statistical Parametric Map 96 software and reformatted for integration into anatomic slices. RESULTS: Virtual movements of the missing limbs produced contralateral primary sensorimotor cortex and central sulcus activations in the patients with upper-limb amputation. Interhemispheric and bilateral activations were found in the patient with both legs amputated. These activation areas were different from the stump activation areas. Additionally, the significance thresholds chosen to generate the activation maps in virtual movements (although individual) were globally the same as those used to detect motor activation in the normal side of the patients. CONCLUSION: Cortical areas devoted to the missing limb seem to persist for several years after amputation. The precentral activations found in our patients are in agreement with the statement that the neural mechanisms involved in the mental representation of an action and in its execution are the same. Data from fMRI can be used to evaluate phantom limb virtual movements and to study cortical reorganization phenomena that can appear with time or as a result of some therapies. In these patients, fMRI data may be useful in assisting the neurosurgeon in the placement of chronic motor cortex electrodes.
Assuntos
Amputados , Córtex Motor/fisiologia , Movimento/fisiologia , Córtex Somatossensorial/fisiologia , Interface Usuário-Computador , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Limiar Sensorial/fisiologia , Córtex Somatossensorial/anatomia & histologiaRESUMO
OBJECTIVE AND IMPORTANCE: Chronic motor cortex stimulation has provided satisfactory control of pain in patients with central or neuropathic trigeminal pain. We used this technique in a patient who experienced phantom limb pain. Functional magnetic resonance imaging (fMRI) was used to guide electrode placement and to assist in understanding the control mechanisms involved in phantom limb pain. CLINICAL PRESENTATION: A 45-year-old man whose right arm had been amputated 2 years previously experienced phantom limb pain and phantom limb phenomena, described as the apparent possibility of moving the amputated hand voluntarily. He was treated with chronic motor cortex stimulation. INTERVENTION: Data from fMRI were used pre- and postoperatively to detect shoulder and stump cortical activated areas and the "virtual" amputated hand cortical area. These sites of preoperative fMRI activation were integrated in an infrared-based frameless stereotactic device for surgical planning. Phantom limb virtual finger movement caused contralateral primary motor cortex activation. Satisfactory pain control was obtained; a 70% reduction in the phantom limb pain was achieved on a visual analog scale. Postoperatively and under chronic stimulation, inhibiting effects on the primary sensorimotor cortex as well as on the contralateral primary motor and sensitive cortices were detected by fMRI studies. CONCLUSION: Chronic motor cortex stimulation can be used to relieve phantom limb pain and phantom limb phenomena. Integrated by an infrared-based frameless stereotactic device, fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication. Pain control mechanisms and cortical reorganization phenomena can be studied by the use of fMRI.
Assuntos
Terapia por Estimulação Elétrica/métodos , Membro Fantasma/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Córtex Motor/fisiologiaRESUMO
Intracerebroventricular morphine analgesic for the treatment of cancer pain was administered, using implanted access ports, in 82 patients from 1984 to January 1994. All of the patients who were selected for treatment were no longer responsive and had developed drug side effects to oral or parenteral opiates in varying doses (60-400 mg/d). The mean follow-up was 66 days (range, 12-443 d) for this series of 82 patients. The effective control of pain was achieved in nearly all of the patients, with only two failures. During the treatment, the daily morphine doses were moderately increased. The initial doses of morphine were a mean of 0.30 mg (range, 0.10-2 mg), and the final doses were a mean of 2.5 mg (range, 0.10-60 mg). The results show that the ratio of the terminal dose to the initial dose increased more rapidly for patients who had a follow-up of over 60 days. However, the increase seems to have been because of the progress of the disease rather than because of drug tolerance.
Assuntos
Bombas de Infusão Implantáveis , Injeções Intraventriculares/instrumentação , Morfina/administração & dosagem , Neoplasias/fisiopatologia , Dor Intratável/tratamento farmacológico , Ventriculostomia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Medição da DorRESUMO
OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.
Assuntos
Neoplasias Encefálicas/cirurgia , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Imageamento por Ressonância Magnética/métodos , Córtex Motor/cirurgia , Dor/cirurgia , Técnicas Estereotáxicas , Cirurgia Assistida por Computador/métodos , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico , Doença Crônica , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain. METHODS: Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus. In this series of patients (n = 159), the daily doses of intrathecal morphine were determined as a function of duration of follow-up. RESULTS: The mean follow-up period was 95 days (range, 5-909 d), the mean starting daily dose of intrathecal morphine was 2.69 mg (range, 1-7.5 mg), and the mean terminal dose was 7.82 mg (range, 1-80 mg). The results demonstrated that only a moderate increase in daily dose of intrathecal morphine was required during the course of treatment (a two- to threefold increase for a 3-mo period). Furthermore, the dose increment was similar for patients followed up for more or less than 60 days. This increase did not result in any central opioid-related side effects, and the pain was managed satisfactorily. CONCLUSION: The requirement for a moderate increase in intrathecal opioid doses reflects the development of tolerance but did not limit the patients' ability to obtain adequate analgesia during the course of their painful disease.
Assuntos
Analgésicos Opioides/administração & dosagem , Morfina/administração & dosagem , Neoplasias/tratamento farmacológico , Dor Intratável/tratamento farmacológico , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Feminino , Seguimentos , Humanos , Injeções Espinhais , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Estudos RetrospectivosRESUMO
This study of the arterial blood of the spinal cord indicates that, of the 62 radicular branches (rami radiculares), at the most seven or eight truly participate in the vascularization of the spinal cord. The authors have observed that the situation and distribution of these branches enable the distinction of three large arterial areas: cervicothoracic, midthoracic, and thoracolumbar. The fixed nature of the intramedullary arterial distribution contrasts with the variability of the afferent arterial supplies. No demarcation permits separation of the vascularization of the spinal cord into anterior and posterior parts. The anastomotic systems situated on the arterial pathways are potentially valuable, but their functioning is problematical. The anterior spinal artery is not continuous, for in the midthoracic region there exists a critical narrow zone. The perimedullary anastomotic system appears insufficient while intramedullary anastomoses are without functional value.
Assuntos
Artérias/anatomia & histologia , Artérias/cirurgia , Medula Espinal/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares/métodos , Anastomose Cirúrgica/métodos , Humanos , Medula Espinal/anatomia & histologiaRESUMO
Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.
Assuntos
Baclofeno/administração & dosagem , Espasticidade Muscular/tratamento farmacológico , Baclofeno/efeitos adversos , Baclofeno/uso terapêutico , Coma/diagnóstico , Overdose de Drogas , Tolerância a Medicamentos , Estudos de Avaliação como Assunto , Humanos , Bombas de Infusão Implantáveis , Injeções Espinhais/efeitos adversos , Esclerose Múltipla/complicações , Hipotonia Muscular/induzido quimicamente , Espasticidade Muscular/etiologia , Transtornos Respiratórios/induzido quimicamente , Traumatismos da Coluna Vertebral/complicações , Fatores de TempoRESUMO
In addition to its possible role as a replacement source in CNS degenerative diseases, neural transplantation may be used to augment the normal production of neuroactive substances. Our laboratory at the University of Illinois at Chicago has shown, in both acute and chronic pain models, that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as the donor source since they produce high levels of both opioid peptides and catecholamines, substances which reduce pain sensitivity when injected locally into the spinal subarachnoid space. The analgesia produced by these transplants probably results from the release of both opioid peptides and catecholamines since it can be blocked or attenuated by both opiate and adrenergic antagonists. Studies indicate that even over long periods there is no apparent development of tolerance. Promising results have been obtained in preliminary clinical studies using allografts of adrenal medulla to relieve cancer pain. This clinical review encompasses results at two Medical Centers-University of Illinois at Chicago and University Paul Sabatier, Toulouse, France-in assessing efficacy of subarachnoid adrenal medullary transplantation for alleviating cancer pain. Our clinical and autopsy data strongly support our previous laboratory studies, i.e., that chromaffin cell transplants into the subarachnoid space represent a promising new approach to the alleviation of chronic pain. It is suggested that further clinical studies are now warranted.
Assuntos
Medula Suprarrenal/citologia , Células Cromafins/transplante , Neoplasias/fisiopatologia , Dor Intratável/cirurgia , Doença Aguda , Analgesia/métodos , Transplante de Células , Células Cultivadas , Doença Crônica , Humanos , Medição da Dor , Espaço SubaracnóideoRESUMO
Intrathecal preparations of morphine for use in intractable pain must contain no preservatives. They are generally formulated in saline (isobaric) or dextrose (hyperbaric) which raises questions of stability. The behaviour of morphine in hyperbaric and isobaric solutions stored in a reservoir for implantation has been examined and the effect of temperature and the time of contact of morphine with the different components of the reservoir as well as the sterilization procedure have been investigated. The best stability was observed with a hyperbaric solution in which there was 15 to 20 times less pseudomorphine than in the isobaric solution, which was found to contain 1% pseudomorphine after 1 month of storage at 37 degrees C in the reservoir. Similar solutions stored in ampoules did not degrade.
Assuntos
Morfina/análise , Pressão Atmosférica , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Indicadores e Reagentes , Morfina/administração & dosagem , Soluções , TemperaturaRESUMO
Adrenal medullary chromaffin cells produce high levels of endogenous opioid peptides. Recent data suggest that transplantation injected locally into the spinal subarachnoid space reduced intractable malignant pain. In order to determine the feasibility, the efficacy and the risks of using adrenal medullary tissue for control of irreducible pain, we have developed a transplantation protocol on cancer pain patients selected when they required chronic intrathecal injection of morphine and progressively increasing doses to maintain the level of analgesic effects. At the present time, our clinical trial involves 8 patients. We report here our initial results (mean follow-up: 5 months). The various data collected before and after the intrathecal administration of chromaffin cells included: 1) Pain evaluation over time, with concomitant narcotic intake, 2) CSF sampling through an implanted access port to determine the following biological parameters: biochemical assay for opioid peptides, cell count and phenotyping of lymphocytes, 3) peripheral blood samples for lymphocyte typing. The results confirm the efficacy of adrenal medullary transplantation into spinal CSF for controlling irreducible cancer pain. Complementary intrathecal and oral morphine were totally stopped in 2 cases and stabilized in 5 others. It seems essential to have an important volume of grafted tissue to achieve analgesia with high levels of metenkephalin in CSF. A progressive decrease in metenkephalin release was observed from 2 to 4 months after the transplantation. Two patients with a long-term follow-up (8 and 12 months) needed another intrathecal chromaffin cell graft.
Assuntos
Medula Suprarrenal/transplante , Sistema Cromafim/fisiopatologia , Neoplasias/fisiopatologia , Peptídeos Opioides/fisiologia , Dor Intratável/cirurgia , Medula Suprarrenal/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalina Metionina/líquido cefalorraquidiano , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nociceptores/fisiopatologia , Medição da Dor , Dor Intratável/fisiopatologia , Espaço Subaracnóideo , Transplante Homólogo , Resultado do TratamentoRESUMO
The increasing trend toward performing minimally invasive neurosurgery may benefit from recent progress in using neuroendoscopic techniques to reduce trauma in patients who have undergone operations. Arterial and venous vessels, especially loops, may compress the central segment and cause hyperactive dysfunction of the nerves. Relationships of the anterior inferior cerebellar artery to the facial and vestibulocochlear nerves and the anterior inferior, and superior cerebellar arteries to the trigeminal nerve were studied. The authors report findings from an endoscopic study performed in cadaver heads via the retrosigmoid and retrolabyrinthine approaches. Arteries and veins were colored by injection of red and blue silicon rubber. The cerebellopontine angle (CPA) was examined using 2.7-mm and 4-mm-diameter rigid endoscopes at viewing angles of 0s degrees , 30s degrees , and 70s degrees . Well-known structures could be identified endoscopically without prior dissection, and the entire CPA could be explored. However, with a retrosigmoid or a retrolabyrinthine approach, the cerebellum had to be retracted to some extent to view the CPA. Moreover, wide dural exposure was required to maneuver the endoscope freely in the CPA. Use of the rigid fiberoptic endoscope is not yet superior to standard surgical techniques for approaching and exploring the CPA.