Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain.

UNLABELLED: Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. IMPLICATIONS: We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

[Benign chronic pain]. / Les douleurs chroniques bénignes.

Recent data indicate that 25 to 30% of the population in industrialized countries suffers from benign chronic pain. Among these patients, 50 to 75% are professionally incapable for varied lengths of time, from a few days to some weeks or months, or even definitively. The aetiology and clinical presentation of chronic benign pain are enormously varied because this definition includes such different pathologies as headache, pain of rheumatologic, postsurgical, organic, and post-zoster origin, lombalgia, radiculalgia, post-amputation pain, neuropathologic pain, causalgia, algoneurodystrophic pain, psychosomatic and idiopathic pain. Since these syndromes and causes of pain could not be discussed individually, they have been grouped according to their neurophysiology and pathophysiology.

Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association.

BACKGROUND: The authors describe the clinical and morphologic patterns in four patients with acquired immune deficiency syndrome (AIDS) who developed intracranial glial tumors. METHODS: This retrospective study reports 70 patients at various stages of human immunodeficiency virus-1 (HIV-1) infection who underwent stereotactic brain biopsy for an intracerebral space-occupying lesion. RESULTS: Of these patients, four had glial tumors: one astroblastoma, two astrocytomas, and one glioblastoma. Glial tumors probably arise from a complex interplay of factors; possibilities include the activation of a dominant oncogene or viral inactivation of a tumor suppressor gene by a viral promoter (like the tat protein), impairment of immune defenses (which facilitates the growth of astrocytomas in acute lymphoblastic leukemia), production of cellular growth factors, cytokines, possible infection of glial cells by HIV, and the potentiation of a coinfectious agent. CONCLUSIONS: These cases illustrate that glial tumors should be considered in the differential diagnosis of brain masses in HIV-1 infection, especially because specific treatment for these tumors is available. Moreover, the occurrence of glial tumors in AIDS patients is not only an important event from a clinical point of view, but may also have implications for the pathogenesis of tumors in AIDS.

Effect of intrathecal baclofen on the monosynaptic reflex in humans: evidence for a postsynaptic action.

Intrathecal baclofen is a very powerful antispastic agent. Its mechanism of action on the monosynaptic H-reflex in spinal patients was investigated. It could inhibit rapidly and profoundly monosynaptic reflexes in lower limbs, but did not modify Ia vibratory inhibition of the soleus H-reflex. To assess more precisely its effect on Ia afferents, an experimental paradigm using Ia heteronymous facilitation of the soleus H-reflex was used. Intrathecal baclofen did not modify the amount of monosynaptic facilitation of the soleus H-reflex brought about by stimulation of the femoral nerve. This demonstrates that the main part of the inhibitory effect of baclofen on the H-reflex in spinal patients is not due to a presynaptic effect, suggesting a postsynaptic site of action.

Primary T-cell malignant lymphoma of the central nervous system. Histological, immunohistochemical and ultrastructural study of a case.

Most primary malignant lymphomas (ML) of the central nervous system (CNS) are derived from B-cells, whereas T-malignant lymphomas (T-ML) primarily arising in the CNS are extremely rare. We report on a patient with a primary T-ML of the CNS localised in the posterior fossa. On the basis of histological, ultrastructural and immunohistochemical studies, this tumour was classified as a pleomorphic T-ML, medium and large cell type with peripheral helper/inducer T-cell phenotype (CD 1-, CD 2+, CD 3+, CD 5+, CD 7-, CD 4+, CD 8-, CD 19-, CD 22-, UCHL 1+/CD 45 RO, L 26-/CD 20, LN 1-/CDW75, LN 2-/CD 74, MB 2-). Furthermore, the positivity of the markers CD 25 and HLA-DR on many medium-sized and large lymphoma cells suggests activation of these cells. The nuclear marker of proliferative activity Ki-67 was expressed in some large cells, whereas the natural killer cell-related markers CD 16 and Leu 7/CD 57 did not react with lymphoma cells. This study emphasises the value of extensive immunohistochemical investigations on frozen and paraffin sections in order to identify and characterize the T-cell malignancies, particularly in their rare CNS location.

Cerebral vasodilation after the thermocoagulation of the trigeminal ganglion in humans.

The resulting changes in the regional cerebral blood flow of 18 patients suffering from idiopathic trigeminal neuralgia and treated by selective thermocoagulation of the trigeminal ganglion were measured by xenon-133 emission tomography. One hour after thermal stimulation, there was an asymmetric increase (P < 0.05) in cerebral blood flow, with a 14.7% mean increase in the ipsilateral cerebral hemisphere (P < 0.001) and a 12.7% mean increase in the contralateral side (P < 0.01). The increase in regional cerebral blood flow was not uniform but was most marked in the ipsilateral middle cerebral artery territory (P < 0.001). There was a slight decrease in cerebellar blood flow, but the reduction in the ipsilateral cerebellar lobe was less than that in the contralateral lobe (P < 0.01). The topography of the most significant changes coincided with that of the innervation of the cerebral vessels by the trigeminal nerve. Several mechanisms are involved in the increase in regional cerebral blood flow, including overall nonspecific activation of the central nervous system and local mechanisms associated with the trigeminal-vascular system.

Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection.

We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue.

Esthesioneuroblastoma with intracranial extension.

The authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the Department of Neurosurgery in collaboration with otorhinolaryngologists. This tumor is most frequently reported as growing inside the nasal cavities, and it can extend to the paranasal sinuses. Cases presenting initially as intracranial tumors have been infrequently reported. At present, histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry. Total resection combined with radiation therapy remains the most satisfactory treatment.

Stereotactic biopsy diagnosis of primary non-Hodgkin's lymphoma of the central nervous system. A histological and immunohistochemical study.

We report 29 cases of primary non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS), 26 of which were diagnosed by stereotactic biopsy and 3 by autopsy. In seven cases the patients were affected by AIDS. Histological examination of this series revealed 15 cases of immunoblastic lymphoma, 12 cases of centroblastic lymphoma, 1 case of lymphoplasmacytic immunocytoma and 1 case of unclassified high grade lymphoma. By immunohistochemistry the B-cell origin of lymphoma cells was demonstrated in 28/29 cases. Eight cases were assigned to the B-cell lineage by demonstration of monotypic surface or cytoplasmic immunoglobulin or of the B-cell phenotype CD22+, CD2-, CD3-, CD5-. In twenty cases the B-cell nature of lymphoma was identified by positivity with two or more anti-B monoclonal antibodies (LN1LN2MB2) and negativity by the anti-T monoclonal antibody UCHL1. The histologically unclassified case was a peripheral T-NHL (CD1-, CD2+, CD3-, CD5+, CD22-). We conclude that histological and immunohistological evaluation of stereotactic biopsy specimens provides sufficient information for diagnosis and phenotypic characterization of primary NHL of the CNS. These lymphomas exhibit important predominance of high-grade malignancy histological types and are nearly always B-cell derived. In addition, we provide further evidence that the panel of monoclonal antibodies LN1, LN2, MB2, and UCHL1 is useful for immunophenotypic characterization of brain lymphomas when only paraffin embedded stereotactic biopsy tissue is available.

Primary lymphoma of the central nervous system. An unresolved therapeutic problem.

From January 1979 to December 1987, 35 cases of primary central nervous system lymphoma (CNS-L) were treated. We recently reviewed these cases focusing on treatment results, treatment modalities, and radiotherapy (RT) or chemotherapy-radiotherapy (CT-RT). Variables such as age, risk factors, presenting symptoms, and histologic condition (all were high-grade or intermediate-grade non-Hodgkin's lymphomas [NHL]) and radiologic data were similar to those of series reported previously. The median survival time was 36 months (+/- 0.2 months) and the disease-free survival (DFS) time was 16 months (+/- 0.12 months). Twelve of 32 patients evaluable for treatment results experienced a recurrence (all but one occurred in the CNS). The DFS rate was 70% for the CT-RT group and 50% for the RT group (median follow-up time, 24 months). Therapeutic results in CNS-L are discussed with special emphasis on a putative role of CT in the management of this rare type of tumor.

[A neurosurgeon's point of view on lumbago]. / Les lombalgies vues par le neurochirurgien.

Low back pain is an important health and economic problem which plagues a large segment of the population of industrialized countries. Etiologic theories based upon tissue damage, and therapeutic measures aimed at eliminating a presumed noxious stimulus are often not efficacious. There is considerable evidence that social and psychological factors play a major role in the symptom complex known as "Low Back pain".

[Influence of medicolegal aspects on the management of the treatment of chronic backache]. / Influence des aspects médico-légaux sur la conduite du traitement des lombalgies chroniques.

After reviewing the different legal definitions in which low back pain is determined to represent a compensable injury, authors evoke the difficulties to prove the reality and the degree of impairment. They recommend to solve conflicting medico legal rules and disability before using other pain relief technics.

[Treatment of intractable pain in ORL cancer]. / Traitement des douleurs irréductibles des cancers de la sphère ORL.

Numerous effective treatments are available to relieve the intractable pain of terminal E.N.T. cancers when aetiological therapies are no longer of any use. These treatments must be prescribed as a progressive therapeutic scale ranging from analgesics, and notably morphine which remains the basic drug, to the classical or stereotactic surgical operations. To these must now be added other routes of administration of morphine (e.g. intraventricularly) which in some cases give unexpected results.

[Effects of delayed-action tetracosactide on chronic pain]. / Effets du tétracosactide retard sur les douleurs chroniques.

Beta 1-24 corticotrophin was the object of an open trial in the "acute" treatment of chronic pain in 22 patients. The analgesic effect of the drug was assessed before and after two weeks of treatment by means of 3 subjective tests: visual analogue scale, numeric scale and Mac Gill pain questionnaire. The results were statistically significant (P less than 0.01). They confirmed that slow-release tetracosactide exerts a beneficial effect on the sensory-discriminative and affective-emotional components of pain. The drug may be prescribed for short periods (1 to 2 weeks) to patients with chronic pain refractory to the usual treatments. Its analgesic effect is immediate and enables a conventional treatment to be instituted.