Motor cortex stimulation for neuropathic pain.

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.

The surgical management of spasticity.

Neurosurgery is only considered for severe spasticity following the failure of noninvasive management (adequate medical and physical therapy). The patients are carefully selected, based on rigorous multidisciplinary clinical assessment. In this we evaluate the contribution of the spasticity to the disability and any residual voluntary motor function. The goals for each patient are: (a) improvement of function and autonomy; (b) control of pain; and (c) prevention of orthopaedic disorders. To achieve these objectives, the surgical procedure must be selective and reduce the excessive hypertonia without suppressing useful muscle tone and limb functions. The surgical procedures are: (1) Classical neuro-ablative techniques (peripheral neurotomies, dorsal rhizotomies) and their modern modifications using microsurgery and intra-operative neural stimulation (dorsal root entry zone: DREZotomy). These techniques are destructive and irreversible, with the reduced muscle tone reflecting the nerve topography. It is mainly indicated when patients have localized spasticity without useful mobility. (2) Conservative techniques based on a neurophysiological control mechanism. These procedures are totally reversible. The methods involve chronic neurostimulation of the spinal cord or the cerebellum. There are only a few patients for whom this is indicated. Conversely, chronic intrathecal administration of baclofen, using an implantable pump, is well established in the treatment of diffuse spasticity of spinal origin. From reports in the literature, we critically review the respective indications in terms of function, clinical progression and the topographic extent of the spasticity.

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies.

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.

[Management of intractable cancer pain: from intrathecal morphine to cell allograft]. / Traitement des douleurs chroniques rebelles d'origine cancéreuse: de la morphinothérapie intrathécale à la thérapie cellulaire.

The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients. Intra-cerebro-ventricular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantation of an intra-ventricular catheter this method is somewhat invasive. Its indications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by cost, the need for specialized maintenance and mechanical malfunctions if implantable drug delivery systems, or by the risk of bacterial contamination and ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intrathecal chromaffin cell allograft is a promising approach for the management of cancer pain refractory to traditional drug therapy and pain lesion surgery. The basic rationale and preclinical studies on experimental pain models have enabled starting prospective clinical trials. Prior to transplantation, handling and preparation of the chromaffin tissue is critical for allograft viability. The initial results of clinical trials with human chromaffin cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincing evidence will require controlled studies. The limitations of this innovative cell therapy and especially the lack of human adrenal gland availability point to the need for new sources of cells. Perspectives include xenogenic or engineered cell lines.

[Treatment of spasticity with the intrathecal administration of baclofen]. / Traitement de la spasticité par administration intra-thécale chronique de baclofène.

Direct intrathecal administration of baclofen in the treatment of severe spasticity was proposed in 1984 by Richard Penn with the objective to carry out a selective spinal distribution of the active principle thus avoiding supraspinal side effects. We presented our first results at the French Language Association of Neurosurgery in 1985 within the framework of a report on "Functional neurosurgery of cerebral palsy" (Neurochirurgie, 1985, 31 (suppl 1): 1-118). This study aims to specify the selection criteria and current indications of this method for the treatment of severe chronic diffused spasticity of spinal and cerebral origin in adults and in children. This report relates to our experience concerning 60 patients (10 children) that benefit from the use of a totally implantable system for chronic administration. The total follow-up of all patients was 48 months (from 3 to 140 months). The initial effective daily amount of baclofen was 156 micrograms/24 hours and progressed in time to reach in the long run 280 micrograms/24 hours, with a very broad interindividual variability from 36 to 1050 micrograms/24 hours. All the patients benefited from a reduction in muscular hypertonicity as well as painful muscular spasms. On the other hand, the functional improvement was very variable from one patient to another and depended primarily on the initial clinical state and the etiology of the spasticity. The results observed were more significant in post-traumatic paraplegia than those secondary to demyelination disease even if they were stabilized with regard to spasticity of spinal origin. This mode of administration currently plays a significant role in the treatment of spasticity of cerebral origin, in particular in children presenting a motor disorder of cerebral origin with spastic prevalence. The current limitations of this type of treatment are technical because of the frequent catheter malfunctions, but are due essentially to the importance and constraint of the multi-disciplinary organization needed for the out-patient follow-up.

Microsurgical anatomy of the internal vertebral venous plexuses.

Few studies have been done about the venous vascularization of the spine since neuroradiologic studies in the 1960s and 70s. The aim of this study was to clarify the topography of the internal vertebral venous plexuses in relation to the posterior longitudinal ligament and the dura. The relationships of the vv. were studied at different levels of the spine. The internal vertebral venous system of seven cadavers was injected with a blue bicomponent silicon rubber. It consisted with an anterior and a posterior venous plexus. At the cervical level, the anterior longitudinal vv. are located in a dehiscence of the periosteal layer, in the lateral part of the spinal canal. At each level, they joined the contralateral one at the midline by a retrocorporeal v. located behind the posterior longitudinal ligament. No vv. were found in the epidural space. There was a major development of the retrocorporeal v. of the axis, but it did not receive any venous drainage from the vertebral body. At the thoracic and lumbar levels, the anterior venous plexuses remain within a dehiscence of the periosteal layer, which is thinner. The retrocorporeal vv. become pre-ligamentous. We did not find any posterior venous plexuses at the cervical level, but they were evident at the thoracic level and became more voluminous and sinusoidal in the lumbar region.

Does intrathecal morphine in the treatment of cancer pain induce the development of tolerance?

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.

[Utilization of thermosettable compounds in anatomic research]. / Utilisation des thermodurcissables en recherche anatomique.

The authors described a method of vascular injection with a coloured silicon rubber. The injected material was a biocomponent silicon elastomer, with ambiant temperature room vulcanizing. It was supple, easily dissequable and diffuse well into all small caliber vessels. The soft pressure injection did not cause neither material collection by vessels rupture nor anatomic structure distortion. This material could constitute an excellent alternative to coloured latex injection.

Intracerebroventricular administration of morphine for control of irreducible cancer pain.

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.

Transplantation of human chromaffin cells for control of intractable cancer pain.

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.

[Chronic spinal cord stimulation in the treatment of neurogenic pain. Cooperative and retrospective study on 20 years of follow-up]. / La stimulation médullaire chronique dans le traitement des douleurs neurogènes. Etude coopérative et rétrospective sur 20 ans de suivi.

The aim of this investigation is to evaluate the long-term spinal cord stimulation (SCS) efficacy and safety, with a 20-years study concerning 692 patients (series I: 279, series II: 413). The series concern 304 arachno-epidural fibrosis, 152 peripheral nerve lesions, 25 amputations pain, 17 plexus brachial lesions, 101 spinal cord lesions, 22 cancer pain, and 71 vascular pain. A multidisciplinary chronic pain evaluation must exclude contra-indications (nociceptive pain, serious drug habituations, psychological problems, unresolved issues or secondary pain). Percutaneous epidural SCS is a screening method if the trial is sufficiently prolonged (3 to 14 days) and if the pain topography is overlapped by induced paresthesias. The immediate global results of the 2 series are similar: respectively 86% and 85% of success one month after implantation. With the same longterm follow-up (mean: 10 yrs, range: 2-20), and the same evaluation criteria, the percentage of long-term global success rate is 54% in series I, and 52% in series II. In the most recent period (1984-1990) concerning 301 patients, the success rate are respectively 68% and 60%. Analysing the results etiologically confirms the therapeutic value of SCS for neurogenic pain secondary to partial deafferentation. For upper limb pain, ipsilateral radicular stimulation is preferable. When the nerve lesion extends to the pre-ganglionic portion (brachial plexus avulsion, herpes zoster) or in cases of pain of spinal or cerebral origin, thalamic stimulation must be considered, after failure of SCS.

[Analysis of the results of surgery and nucleolysis using papain in 1085 cases of lumbar disk hernias]. / Analyse des résultats de la chirurgie et de la nucléolyse à la papaïne dans 1,085 cas de hernies discales lombaires.

1,085 patients have been treated for intervertebral disc herniation with lombo-sciatica: in 751 cases surgical discectomy without laminectomy has been performed with or without microscope; 334 underwent papain nucleolysis. The two clinical groups were separated on clinical and radiographic backgrounds: nucleolysis was performed in patients with no motor disturbance, no stenosis of the lumbar canal, no displaced fragment; the other patients received surgical treatment. The results were evaluated according to MacNab's criteria with a follow-up of 12 to 84 months (mean 17.2 months). The results after surgical treatment were excellent in 53.8% and good in 36.8% of the cases. For papain treatment they were excellent in 32.7% and good in 38.8% of the cases. Papain nucleolysis therefore appears to be an efficient method for the treatment of intervertebral disc herniations associated with lombo-sciatica but, overall, gives poorer results than surgery in spite of a strict selection procedure. In this study, complications due to papain nucleolysis were restricted to chemical spondylodiscitis (5 cases) and to 2 benign allergic syndromes. Statistical analysis of all the cases and multifactorial correlation research pointed out the importance of "workmen's compensation" as prognostic factor. Since this study, 90% of the patients presenting with disc herniation associated with lombo-sciatica recalcitrant to medical treatment undergo surgical discectomy; papain nucleolysis is reserved for sub-ligamentary and non-displaced forms without stenosis of the lumbar canal and represent 10% of our current population.

Chronic intrathecal baclofen administration for control of severe spasticity.

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.

Human brain and spinal cord scan after intracerebroventricular administration of iodine-123 morphine.

[123I]iodomorphine (IMPH) was administered intracerebroventriculary (i.c.v.) in eight patients treated by i.c.v. morphinotherapy (i.c.v.m.). Scans obtained by gamma-scintigraphy over 1 h post-injection showed only a slight diffusion of IMPH beyond the ventricular system, particular attention being paid to the spinal cord. These data agree well with induced i.c.v.m. analgesia (mean latency 20 min) and biological results such as HPLC assay of morphine in the lumbar cerebrospinal fluid, supporting the action of morphine only on the central opiate receptors.

CSF morphine levels after lumbar intrathecal administration of isobaric and hyperbaric solutions for cancer pain.

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.

Chemonucleolysis for herniated cervical disc.

The authors treated 38 cases with cervical disc prolapse and discoradicular pain by percutaneous chemonucleolysis. Material and procedure are described and the results of 31 cases with a follow-up between 3 and 52 months analysed. The global results were excellent. In detail the results are analysed according to symptomatology, aetiology, findings of discography and the dose of enzyme used.

[Chemonucleolysis in the treatment of surgical sciatica]. / La chémonucléolyse dans le traitement des sciatiques chirurgicales.

Enzymatic dissolution of nucleus pulposus by percutaneous injection of a papain preparation is now used frequently to treat lumbosacral disc hernias responsible for resistant sciatica. Mechanisms of action and techniques are reviewed, and the importance of applying strict criteria for indications for use emphasized. The method should be reserved for nerve root sciatica resistant to medical treatment or physiotherapy, and it constitutes the last stage of conservative treatment. Exclusion criteria are mainly "excluded" disc lesions, major dysfunction or associated spinal vertebral canal stenosis. The optimal indication is represented by the subacute disc hernia in the young. This alternative to open surgery in no way compromises the results in case of failure. Results obtained in a personal series of 150 cases are analyzed comparatively with those reported in the literature.