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In two patients, a 60-year-old woman and a 63-year-old man, cerebral blindness was diagnosed. The first patient developed the disorder shortly after cerebral angiography was carried out to diagnose a carotid-cavernous fistula. The symptoms disappeared after three days. The second patient suffered from a reversible posterior leuko-encephalopathy syndrome. He recovered his vision without specific treatment. Cortical or cerebral blindness is a form of blindness caused by a lesion in the cerebral part of the visual pathways. Although in itself rare, cerebral blindness occurs frequently as a complication of non-neurologic diseases or interventions. Physicians who are unaware of this syndrome tend to diagnose these patients as 'hysteric', since normal pupillary reactions and normal eye movements accompany the loss of vision. If the blindness is not caused by an ischaemic infarct, it is usually reversible.

Objective: To describe the comparison of multiple and single pain ratings in patients with complex regional pain syndrome type I (CRPS I)., Design: Correlation, agreement, and reliability analyses were performed between the average pain intensity measured 3 times a day over a course of 4 days and one single pain rating (designated the "recalled average" pain, as assessed by the patient) before treatment and at 1-, 3-, and 6-month periods after treatment., Patients: The patient population consisted of 54 patients with CRPS I in a randomized trial., Results: The results show that both measurements correlate and have excellent agreement. Furthermore, both ratings measure significant pain reduction after treatment; "recalled average" pain, however, reflects greater change in pain intensity., Conclusions: In patients with CRPS I a single pain rating is an accurate predictor of the average pain measured by a multiple pain-rating test. Moreover, both assessments are accurate enough to determine changes in pain over time with an effective treatment.

Reflex sympathetic dystrophy (RSD), also known as complex regional pain syndrome type I (CRPS I), is a disabling neuropathic pain syndrome. Controversy exists about the effectiveness of therapeutic interventions for the management of RSD/CRPS I. In order to ascertain appropriate therapies we conducted a review of existing randomized controlled trials of therapies for this disabling disease. Eligible trials were identified from the Cochrane, Pubmed, Embase and MEDLINE databases from 1966 through June 2000, from references in retrieved reports and from references in review articles. Twenty-six studies concerning treatment modalities were identified. Eighteen studies were randomized placebo-controlled trials and eight studies were randomized active-controlled trials. Three independent investigators reviewed articles for inclusion criteria using a 15-item checklist. Seventeen of the trials were of high quality according to the 15-item criteria. There was limited evidence for the effectiveness of these interventions because of the heterogeneity of treatment modalities. The search for trials concerning prevention of RSD/CRPS I resulted in two eligible studies. Both were of high quality and dealt with different interventions. There is limited evidence for their preventive effect., (Copyright 2002 European Federation of Chapters of the International Association for the Study of Pain.)

Objective: This study was designed to investigate whether Complex Regional Pain Syndrome type I (CRPS I) could be linked to any previous infection., Patients: Fifty-two patients with CRPS I of one extremity were screened for the presence of antibodies against mostly neurotropic microorganisms., Results: Of these 52 patients, none had antibodies against Treponema pallidum, Borrelia burgdorferi, or HTLV-1. Only four patients were positive for Campylobacter jejuni. For cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and Toxoplasma gondii, seroprevalences were similar to control values. The total seroprevalence of Parvovirus B 19 in our CRPS population was 77%, which was significantly higher than in an independent Dutch population group (59%). Seroprevalence in lower extremity CRPS 1 (94%) was significantly higher than in upper extremity CRPS I patients (68%). In this study all patients were seropositive for varicella zoster virus (VZV) antibodies, but a high prevalence of VZV antibodies is similar to its prevalence in a normal population (>90%)., Conclusions: In this study we found a significantly higher seroprevalence of Parvovirus B19 in CRPS I and this is most striking in lower extremity CRPS I patients. Further serologic research in other geographic areas is needed to provide additional information about a potential role of Parvovirus B 19 or other microorganisms in the etiopathogenesis of CRPS I.

Objective: The aim of the current study was to examine the relation between catastrophizing and pain intensity, pain-related disability, and psychological distress in a group of patients with chronic pain, controlling for the level of physical impairment. Furthermore, it was examined whether these relations are the same for three subgroups of chronic pain patients: those with chronic low back pain, those with chronic musculoskeletal pain other than low back pain, and those with miscellaneous chronic pain complaints, low back pain and musculoskeletal pain excluded., Design: Correlational, cross-sectional., Patients and Setting: Participants in this study were 211 consecutive referrals presenting to a university hospital pain management and research center, all of whom had a chronic pain problem., Results: Overall, chronic pain patients who catastrophize reported more pain intensity, felt more disabled by their pain problem, and experienced more psychological distress. Regression analyses revealed that catastrophizing was a potent predictor of pain intensity, disability, and psychological distress, even when controlled for physical impairment. No fundamental differences between the three subgroups were found in this respect. Finally, it was demonstrated that there was no relation between physical impairment and catastrophizing., Conclusions: It was concluded that for different subgroups of chronic pain patients, catastrophizing plays a crucial role in the chronic pain experience, significantly contributing to the variance of pain intensity, pain-related disability, and psychological distress. These relations are not confounded by the level of physical impairment. Some clinical implications of the results are discussed. Finally, the authors concluded that these results support the validity of a cognitive-behavioral conceptualization of chronic pain-related disability.

Phantom pain, a form of neuropathic pain, is caused by damage to somatosensible afferent nerve fibres in the peripheral or central nervous system. Often, the pain cannot be satisfactorily treated with nonsteroidal anti-inflammatory drugs. Dependent on the underlying mechanism the pain is treated with either antidepressants (for more or less continuous pain) or anti-epileptics (for paroxysmal pain). Of the antidepressants, the tricyclic antidepressants are the best studied and most prescribed. The activity of new drugs, such as the selective serotonin reuptake inhibitor paroxetine as well as venlafaxine, has yet to be clearly shown. Of the anti-epileptics, carbamazepine and phenytoin are the most prescribed. New drugs which provide greater pain relief than the placebo are oxcarbazepine, gabapentine and lamotrigine. Other effective drugs for phantom pain are: gamma-butyric acid agonists (baclofen), opiates (morphine preparations with a regulated release; phentanyl patch), the N-methyl-D-aspartate receptor antagonist amantadine, transdermally administered clonidine and locally applied lidocaine.

Study Design: A prospective double-blind randomized trial in 28 patients., Objectives: To assess the clinical effect of percutaneous intradiscal radiofrequency thermocoagulation for reducing pain, functional disability, and physical impairment in patients with chronic discogenic low back pain., Summary of Background Data: Chronic discogenic low back pain is a challenging problem in western countries. A treatment option is radiofrequency heating of the affected disc. Its clinical efficacy has never been formally tested in a controlled trial., Methods: Twenty-eight patients with a history of at least 1 year of chronic low back pain were selected on the basis of a diagnostic anesthetization of the lower intervertebral discs. Only patients with one putative painful level were selected and randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (n = 13) received a 90-second 70 C lesion of the intervertebral disc. Patients in the control group (n = 15) underwent the same procedure, but without use of radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator., Results: Eight weeks after treatment, there was one success in the radiofrequency group (n = 13) and two in the control group (n = 15). The adjusted and unadjusted odds ratio was 0.5 and 1.1, respectively (not significant). Also, visual analog scores for pain, global perceived effect, and the Oswestry disability scale showed no differences between the two groups., Conclusions: Percutaneous intradiscal radiofrequency thermocoagulation (90 seconds, 70 C) is not effective in reducing chronic discogenic low back pain.

Objective: To assess interobserver reliability of two expert headache neurologists when examining the cervical spine of patients with headache., Background: The diagnosis of cervicogenic headache involves the physical examination of the cervical spine., Methods: Twenty-four patients diagnosed as having migraine, tension-type headache, or cervicogenic headache were included in the study. After interview, each patient's cervical spine was examined in a structured way. Reliability was assessed by Cohen's kappa., Results: Reduced range of motion in the cervical spine showed kappa scores indicating moderate agreement. Provocation of headache revealed moderate-to-substantial agreement. Assessment of zygapophyseal joint pressure pain showed slight-to-fair agreement. The kappa values of the circumscribed characteristic tender points showed agreement ranging from "not better than chance" to "substantial agreement.", Conclusions: Our study showed that the interobserver reliability of expert headache neurologists was satisfactory in the majority of the physical examination tests of the cervical spine in patients with different headache syndromes. However, standardization of the clinical tests in order to improve their reliability is recommended.

Ther term cervicogenic headache (CEH) was introduced by Sjaastad and co-workers in 1983. In 1990 Sjaastad et al. published diagnostic criteria for CEH. In 1998 refinements of these criteria were published, emphasising the use of diagnostic nerve blocks in patients with CEH as important confirmatory evidence. However, the standardisation of diagnostic nerve blocks in the diagnosis of CEH remains to be defined. Herein we present an overview of diagnostic nerve blocks in the cervical area. Suggestions as to their role in the diagnosis of CEH are given.

The project "Infusion Therapy at Home" studied the practice of parenteral infusion therapy at home. Among the treatment modalities was the administration of morphine infusions to terminally ill patients. With infusion of morphine, patients were pain-free on 73% of the treatment days. Quality of care, quality of life, and costs were acceptable.

To assess the interobserver reliability in distinguishing cervicogenic headache (CEH) from migraine without aura and tension-type headache we conducted a study keeping as closely as possible to daily clinical practice. In contrast to other reliability studies, which use data from clinical patient records or semi-structured interviews recorded on videotape ('in vitro' design), we examined 'live' patients ('in vivo' design). Twenty-four headache patients participated in our 'in vivo' design experiment. During a session, each physician performed a physical examination and queried six patients in succession using a semi-structured interview. Diagnosis was carried out in accordance with the International Headache Society (IHS) criteria and the criteria from Sjaastad and co-workers. Kappa statistics were used: 0.83 between the expert headache neurologists; 0.74/0.73 between the expert anesthesiologist in (head) pain treatment and both expert neurologists respectively; kappa ranged from 0.43 to 0.62 between the other physicians. The results of our 'in vivo' design study show that the reliability in diagnosing CEH, when strictly applying the criteria from Sjaastad and co-workers, is similar to the reliability in diagnosing migraine and tension-type headache according the IHS criteria.

Reflex sympathetic dystrophy (RSD) is a relatively common disabling disorder of unknown pathophysiology. From a cohort of 52 patients, carefully selected to fulfill the recently formulated diagnostic criteria for RSD, venous blood samples were taken for typing of class I and II major histocompatibility antigens. The frequency of HLA-DQ1 was found to be significantly increased compared with control frequencies. The association provides an indication for an organic basis of RSD.

Study Design: A prospective double-blind randomized trial in 31 patients., Objectives: To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain, functional disability, and physical impairment in patients with back pain originating from the lumbar zygapophysial joints., Summary of Background Data: Chronic low back pain is a major health problem in the industrialized world. A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints. Its clinical efficacy has never been formally tested in a controlled trial., Methods: Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (15 patients) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3, L4, and L5. Patients in the control group (n = 16) underwent an the same procedure but without use of a radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator., Results: Eight weeks after treatment, there were 10 success patients in the radiofrequency group (n = 15) and 6 in the sham group (n = 16). The unadjusted odds ratio was 3.3 (P = 0.05, not significant), and the adjusted odds ratio was 4.8 (P < 0.05, significant). The differences in effect on the visual analog scale scores, global perceived effect, and the Oswestry disability scale were statistically significant. Three, 6, and 12 months after treatment, there were significantly more success patients in the radiofrequency group compared with the sham group., Conclusions: Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain, both on a short-term and a long-term basis.

Object: The aim of the study was to assess retrospectively the clinical efficacy and possible adverse effects of electrical spinal cord stimulation (SCS) for the treatment of patients with reflex sympathetic dystrophy (RSD)., Methods: Twenty-three patients who suffered severe pain due to RSD were included in the study. The SCS system was implanted only after a positive 1-week test period. The visual analog scale (VAS) score for pain (1-10) was obtained in all patients prior to treatment, 1 month postimplantation, and at last follow up. At final follow-up examination, patients were asked to rate the effect of their treatment on the 7-point global perceived effect scale. Eighteen (78%) of 23 patients treated between 1991 and 1997 reported improvement during the test period. Permanent implantation of SCS system was not performed in the other five patients. Complications occurred in nine (50%) of 18 patients. The system was removed in three patients after implantation (17%). At the end of follow up (mean 32 months) 15 patients still had an implanted system. The mean pain score had decreased from 7.9 to 5.4 (p<0.001). In the other eight patients the pain score had not changed significantly. In 13 patients (57%) in whom the SCS system was implanted, clinical status had much improved or improved; these cases were regarded as successful., Conclusions: In this retrospective series, the majority of patients with RSD reported a subjective improvement after implantation of an SCS system.

The present study assessed the clinical efficacy of radiofrequency cervical zygapophyseal joint neurotomy in patients with cervicogenic headache. Fifteen consecutive patients with cervicogenic headache were treated and then assessed one week prior to treatment and, at short-term (8 weeks), intermediate (mean 8.8 months) and long-term (mean 16.8 months) follow-ups. The following were taken as outcome parameters: Visual Analogue Scale (VAS), 7-point Verbal Rating Scale (VRS), number of headache days per week and analgesic intake per week. The results of this study showed that radiofrequency neurotomy of the cervical zygapophyseal joints significantly reduced headache severity in 12 (80%) patients, both at short-term and long-term follow-up assessed by 7-point VRS. Mean VAS decrease was 31.4 mm (p < 0.001) and 53.5 mm (p < 0.0001) respectively in this period. The average mean number of headache days per week decreased from 5.8 days to 2.8 days (p = 0.001) and the average analgesic intake per week showed a reduction from a mean of 17.5 tablets to a mean of 3.4 tablets (p = 0.003). A definitive conclusion about the clinical efficacy of this treatment can only be drawn from a randomized controlled trial.

T cells expressing the gamma delta T cell receptor have been implicated in anti-Epstein-Barr virus (EBV) immunity and in the pathogenesis of autoimmune diseases of the central nervous system. However, they have never been isolated from human brain tissue for direct analysis. We now report a 6-year-old girl with EBV-associated posttransplantation lymphoproliferative disease involving inflammatory brain lesions. A high proportion of gamma delta T cells was found in the blood and in a brain lesion. Cultured T cell lines were found to have a remarkably high frequency of responsiveness to an EBV-transformed line, with a 17-fold enrichment in the brain lesion. These T cells expressed predominantly the gamma delta T cell receptor and mediated non-MHC-restricted cytotoxicity against EBV-infected target cells. These results provide the first demonstration of an association of gamma delta T cells with a posttransplantation lymphoproliferative disease and suggest a role of gamma delta T cells in mediating inflammatory processes in the brain.

A case of severe, acute parkinsonism occurring in a 60-year-old man after cessation of chronic alcohol consumption, is reported. He recovered completely in 3 months without specific therapy. The literature on alcohol withdrawal parkinsonism including nine other cases, is reviewed.

Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.

We report a case of spontaneous posture-dependent headache associated with primary intracranial hypotension (PIH). The spinal fluid pressure was 0 cm H2O. Radioisotope cisternography showed that the cerebrospinal fluid flow was normal at the level of the spinal cord, but was suggestive for a hyperabsorption or leakage of CSF below the craniocervical junction.

Monoclonal antibodies directed against CD3, a T cell-specific surface molecule essentially required for activation of these cells, are highly mitogenic for resting human peripheral blood T lymphocytes. A predetermined optimal concentration of anti-CD3 monoclonal antibody WT32 was employed to activate T cells cultured in limiting-dilution microcultures containing irradiated feeder cells and exogeneous interleukin 2. Frequencies of cells triggered into clonal expansion by WT32 under these culture conditions were 0.57 to 0.72 and 0.90 to 1.10 in peripheral blood mononuclear cells and E rosette-positive cells, respectively. It appeared that WT32 could induce virtually every human peripheral blood T lymphocyte to expand into a clonal progeny of 5 to 40 X 10(4) cells in 14 to 18 days of culture. This progeny was tested for cytolytic effector function with 51Cr-labeled murine P815 targets in the presence of PHA to detect all cytotoxic T lymphocytes (CTL) regardless of specificity, and was also assayed for natural killer like activity against K562 target cells. Frequencies of cells in the human peripheral blood T cell compartment giving rise to a clonal progeny expressing CTL function was 1/3, whereas 1/6 to 1/5 expanded into effector cell populations possessing NK activity. Frequency analysis of CD4-positive and CD8-positive populations, activated by WT32 in limiting dilution microcultures, demonstrated that 1 to 6% of the CD4-positive and 100% of the CD8-positive peripheral blood T lymphocytes expanded into CTL.

Two experiments were performed to estimate the number of alleles at the two incompatibility loci of rye in the variety 'Halo'. In one experiment I1 progenies from enforced selfing under controlled conditions were isolated. In the other experiment a genotype, homozygous at both incompatibility loci, was used as pollinator for a sample of the 'Halo' population, which was regarded as an equilibrium population. Genotypes, which are homozygous at both incompatibility loci, can be found after selfing. The estimate for the number of alleles was 6 to 7 at one locus and 12 to 13 at the other locus.

For daughter groups of 15 test bulls, controls of paternity were performed by using blood group factors and biochemical polymorphisms. Data of incorrectly assigned daughters influenced the estimation of breeding values, heritabilities and correlations for milk performance traits. Formulae are given that show the effects of variable misidentification rates on estimation of breeding values, selection intensities, heritabilities, and genetic gains. For example, for milk fat yield, the genetic gains drop at a misidentification rate of 15% between 8.7% (for h2 = .5) and 16.9% (for h2 = .2) below values attained without misidentifications. Consequently, decreasing misidentification rates in progeny of test bulls can be used to diminish the progeny size per test bull for constant genetic gain, to achieve more precise ranking of all or distinct test bulls according to their "true" breeding values and(or) to increase the number of test bulls by using the same amount of test inseminations and the same precision of ranking. Actions to reduce misidentification rates in cattle populations are discussed.

The in vitro effects of cyclosporin A, prednisolone, and anti-CD4 monoclonal antibody WW.T4 on myelin basic protein-specific human CD4+ cytolytic T lymphocyte clones were studied. Functional assays of antigen-specific proliferation, induction of specific lysis, cytolysis itself, and interferon-gamma production were done. Prednisolone decreased secretion of interferon-gamma by the clones and blocked specific proliferation; the latter could, however, be overcome by the addition of exogenous interleukin 2. It did not influence cytolytic properties. In contrast, cyclosporin A and WW.T4 blocked the four antigen-specific functions of the autoimmune myelin basic protein-specific human T cell clones measured.

In the present report we describe the isolation and characterization of stable, long-term, human T-lymphocyte clones specific for myelin basic protein (MBP) from multiple sclerosis (MS) patients. Isolation of these clones appeared possible only by seeding peripheral blood mononuclear cells into a limiting dilution microculture system containing MBP, autologous irradiated cells and Interleukin-2 (IL-2), thereby minimizing effects of putative suppressor cell populations. All clones obtained were of the CD4+ phenotype. The majority was capable of MBP-specific cytolysis, tested with 51Chromium-labeled autologous Epstein-Barr virus (EBV)-transformed B-cells, coated with MBP, as targets. A few other clones had natural killer (NK) function. All clones produced Interleukin-2 (IL-2) upon adequate stimulation.

Cellular immune reactions against the autoantigen myelin basic protein (MBP) are strongly implicated in the occurrence of postinfectious and postvaccination encephalomyelitis. Clinical autoimmune encephalomyelitis in experimental animals can be transferred with cloned MBP-specific cytolytic major histocompatibility complex Class II-restricted T lymphocytes. The HLA restriction pattern of specific proliferative and cytolytic functions of two human MBP-specific cytotoxic T lymphocyte clones, derived from two different multiple sclerosis patients, was analyzed in detail. Using monoclonal antibodies against various HLA gene products and allogeneic Epstein-Barr virus-transformed B cells as antigen-presenting cells and as targets for cytolysis, it was found that MBP-specific functions of the T cell clones was restricted by HLA class II antigens, and, more specifically, by molecules encoded for by DR locus genes.

In this report, we describe for the first time an epitope common to human myelin basic protein (H.MBP), a structural component of central nervous system myelin, and T lymphocyte CD3, an activation molecule important in signal transduction. This cross-reactive determinant was recognized by a murine mAb WW.B1, which was raised against H.MBP. WW.B1 recognized PBMC and the Jurkat T leukemic cell line, immunoprecipitated both H.MBP and a complex indistinguishable from CD3, and possessed the same biologic properties--induction of T lymphocyte proliferation and inhibition of CTL function--as commercially available anti-CD3 antibodies. It is likely, however, that the epitope recognized by WW.B1 is distinct from those recognized by the anti-CD3 mAb OKT3 and anti-Leu-4. Although the biologic importance of this common determinant awaits further clarification, it is conceivable that autoimmunization to MBP could induce similar immunoregulatory antibody specificities.

Cytolytic T lymphocyte precursors (CTL-p) and natural killer precursors (NK-p) in the CSF of 15 MS patients and 11 patients with other neurologic disorders (OND) were quantitatively assessed, using a T-lymphocyte microculture system that allows clonal expansion of all human T cells. CSF CTL-p and NK-p frequencies were higher in patients with OND of inflammatory nature than in patients with noninflammatory OND. In all MS patients, these frequencies were higher in the CSF than in their peripheral blood. Surprisingly, in all patients studied, the CSF contained a substantial number of CTL-p with a helper (CD4+) phenotype.

The analysis of variance normally is conducted under the assumption of no correlations between residuals. Sometimes this assumption is violated in plant breeding experiments. If it is ignored, the estimates of mean squares and variance components are biased. For some restricted models the correlation is estimated from experiments with Gerbera, tulips and potatoes. Often a positive correlation was found, but never a negative one. The consequences of such correlations are discussed.

Equations for the genotypic frequencies at equilibrium in two- and kappa-locus incompatibility systems are given on the basis of an equal fertility of all genotypes. The number of alleles may be different at each locus. The results are compared with those of Charlesworth (1979), who used another approach with unequal fertility.