Risk of fracture in patients with Guillain-Barré syndrome.

UNLABELLED: The aim of this study was to evaluate fracture risk in patients with Guillain-Barré syndrome (GBS). No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture. INTRODUCTION: Symptoms of Guillain-Barré syndrome (GBS) may vary from mild difficulty in walking to complete paralysis, which may increase the risk of fractures. Therefore, the aim of this study was to evaluate fracture risk in patients with GBS. METHODS: We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with GBS was matched by year of birth, sex, and practice, up to six patients without a history of GBS. Outcome measure was any fracture. RESULTS: There were no associations between GBS and any fracture, adjusted hazard ratio (AHR) 1.01 (95 % confidence interval [CI] 0.77-1.33), or osteoporotic fracture, AHR 0.76 (95 % CI 0.50-1.17), compared with controls. Stratification to gender, age, and duration since diagnosis did not show an association either. Only for GBS patients using pain treatment, risk of fracture was doubled AHR 1.97 (95 % confidence CI 1.21-3.21) compared with controls. The risk of fracture in GBS patients exposed to pain treatment was equivalent to risk of fracture among controls exposed to pain treatment. CONCLUSIONS: No association with risk of fracture was observed for GBS patients compared with controls. Only GBS patients using pain treatment had a doubled risk of fracture, but their risk was equivalent to fracture risk among controls exposed to pain treatment.

Risk of fracture in patients with muscular dystrophies.

UNLABELLED: The aim of the study was to determine fracture risk in incident muscular dystrophy (MD) patients. Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Risk further increased among elderly and female patients and among patients exposed to oral glucocorticoids. INTRODUCTION: Muscular dystrophies (MDs) are inherited diseases causing muscle weakness and thereby increase the risk of falling and detrimental effects on bone. Both are recognised risk factors for fracture. Therefore, the aim of this study was to determine the hazard ratio of fracture in patients with MD. METHODS: We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2012). Each patient with MD was matched by year of birth, sex and practice to up to six patients without a history of MD. Outcome measure was all fractures. RESULTS: As compared with control patients, risk of any fracture was statistically significantly increased in MD patients (adjusted hazard ratio [AHR], 1.40; 95 % confidence interval [CI], 1.14-1.71). An increased risk of fracture was observed among MD patients with female gender (AHR, 1.78; 95 % CI, 1.33-2.40) and an increasing age as compared with control patients. Stratification to Duchenne MD showed no association with fracture, whereas risk of fracture was increased twofold among patients with myotonic dystrophy (AHR, 2.34; 95 % CI, 1.56-3.51). MD patients had an almost tripled risk of fracture when they used oral glucocorticoids in the previous 6 months as compared to non-users with MD. CONCLUSION: Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Especially in older age groups and female gender, the fracture risk of MD versus non-MD patients is increased, whereas exposure to glucocorticoids further increased fracture risk among MD patients.

Risk of fracture in patients with Parkinson's disease.

UNLABELLED: The aim of the study was to determine fracture risk in incident Parkinson's disease (PD) patients. This study showed that fracture risk assessment may be indicated among patients with PD, in particular when they have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics, or have a history of fracture, falling, low body mass index (BMI) or renal disease. INTRODUCTION: PD is a movement disorder associated with falling and detrimental effects on bone. Both are recognized risk factors for fracture. Therefore, the aim was to determine fracture risk in incident PD patients stratified by treatment, severity, duration of disease and related comorbidities. METHODS: We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2011). Each PD patient was matched by age, sex, calendar time and practice to a control patient without history of PD. RESULTS: We identified 4,687 incident PD patients. Compared to controls, a statistically significant increased risk was observed for any fracture (adjusted hazard ratio [AHR], 1.89; 95 % confidence interval [CI], 1.67-2.14), osteoporotic fracture (AHR, 1.99; 95 % CI, 1.72-2.30) and hip fracture (AHR 3.08; 95 % CI, 2.43-3.89). Fracture risk further increased with history of fracture, falling, low BMI, renal disease, antidepressant use and use of high-dose antipsychotics. CONCLUSION: This study showed that incident PD patients have a statistically significant increased risk of fracture. Therefore, fracture risk assessment may be indicated among PD patients, who, besides the general risk factors for fracture, like increasing age and female gender, have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics or have a history of fracture, falling, low BMI or renal disease.

The reliability of transcranial duplex scanning in parkinsonian patients: comparison of different observers and ultrasound systems.

PURPOSE: To establish the inter-observer and intra-transducer reliability of "on-line" and "off-line" assessment of substantia nigra (SN) and raphe nuclei (RN) by transcranial duplex scanning (TCD) in a mixed study population. MATERIALS AND METHODS: Out-patient neurology department of the University Hospital Maastricht. In total 24 subjects were investigated: 9 patients with idiopathic Parkinson's disease, 10 with parkinsonism from yet unclear origin, 1 with essential tremor and 4 healthy volunteers. Each patient was assessed four times by two independent experienced sonographers using two different ultrasound devices: SONOS 5500 and iU22; both Philips, Eindhoven, The Netherlands. The echointensity of the SN is evaluated qualitatively and quantitatively and the RN only qualitatively. 1. In the "on-line" assessment we determined: a) the inter-observer agreement of the four possible combinations. b) the intra-observer agreement of both sonographers using two different ultrasound systems. 2. In the "off-line" assessment a third sonographer re-examined the stored images. We determined the inter-observer agreement of the third sonographer with the "on-line" assessment of the other two sonographers. Cohen's k value was calculated for the agreement. RESULTS: 1a) The "on-line" inter-observer agreement of the four possible combinations of sonographer and transducer was: kappa 0.23 - 0.39 for the qualitative evaluation of the SN, kappa 0.31 - 0.56 for the quantitative evaluation of the SN and kappa 0.03 - 0.15 for the evaluation of the RN. 1b) The "on-line" intra-observer agreement was: kappa 0.53 - 0.67 for the qualitative evaluation of the SN, kappa 0.55 - 0.76 for the quantitative evaluation of the SN and kappa 0.45 - 0.47 for the evaluation of the RN. 2. The "off-line" inter-observer agreement was: kappa 0.32 - 0.67 for the qualitative evaluation of the SN, kappa 0.53 - 0.61 for the quantitative evaluation of the SN and kappa 0.08 - 0.33 for the evaluation of the RN. CONCLUSION: For the SN we found mediocre accordance comparing both observers "on-line" with each other as well as comparing an "off-line" observer with both "on-line" observers. On the whole, the inter-observer and intra-observer agreement were moderate to substantial for the evaluation of the SN. "On-line" and "off-line" comparisons yielded comparable results. The agreement for the evaluation of the RN, on the contrary, was considerably lower. Our findings indicate that this TCD technique is not yet ready for the application in large population screenings.

Transcranial sonography for the discrimination of idiopathic Parkinson's disease from the atypical parkinsonian syndromes.

We reviewed eight studies on transcranial sonography (TCS) as a tool for differentiating idiopathic Parkinson's disease (IPD) from atypical parkinsonian syndromes (APS) and included some first data on TCS findings in the subforms of PSP. Changes of specific structures on TCS like the substantia nigra (SN), lenticular nucleus (LN), and the third ventricle are discussed as well as how they can contribute to differentiate between IPD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Lewy body disease (LBD), and corticobasal degeneration (CBD). We finish with an algorithm that may be used to employ TCS as a diagnostic instrument delineating IPD from the APS and discerning among the APS themselves. As TCS is at present the most promising tool for this particular diagnostic problem, this algorithm might be a suitable hypothesis to study in future research.

Predictive value of clinical characteristics in patients with suspected cauda equina syndrome.

BACKGROUND AND PURPOSE: Overlooking a potential diagnosis of cauda equina syndrome (CES) can result in severe long-term neurologic deficits. There is a growing trend to order urgent magnetic resonance imaging (MRI) scans of the lumbar spine in any patient presenting with signs suspicious for CES. A substantial number of these MRI scans do not show cauda compression. The purpose of this study is to assess whether clinical characteristics can predict MRI-confirmed cauda compression. METHODS: We retrospectively studied 58 consecutive cases of suspected CES who presented at our hospital's emergency room. RESULTS: Eight of 58 patients had cauda compression on MRI. When measured, MRI + CES patients (6) had more than 500 ml urinary retention. Moreover, when these patients had at least two of the following characteristics: bilateral sciatica, subjective urinary retention or rectal incontinence symptoms, MRI was more probable to demonstrate cauda compression with an OR of 48.00, 95% (CI 3.30-697.21), which was also significant (P of 0.04). The presence of other symptoms or signs alone was not significantly different between both groups. CONCLUSION: In our series, urinary retention of more than 500 ml alone or in combination with two or more specific clinical characteristics were the most important predictors of MRI confirmed cauda compressions.

Parkinson's disease, levodopa-use and the risk of melanoma.

Since the early 1970s, the literature has suggested an association between Parkinson's Disease (PD) and/or levodopa-use and an increased risk for the development of malignant melanoma. In some countries, this possible association has even led to a warning in the drug insert leaflet of the possible risk. Recently, five studies have been published that have investigated both associations and three conclusions can be drawn. Firstly, there appears to be an increased risk in the development of melanomas in patients with PD. Secondly, this increased risk is already present before the PD is diagnosed. Finally, it is unlikely that levodopa plays any role in this phenomenon. It is not known which factors are responsible for this increase in the development of melanomas in PD patients and this needs further investigation. We recommend the removal of the warning from the drug insert leaflet, since this can lead to unnecessary fear on the part of the patients and physician resistance to prescribing this medication.

The ictal bradycardia syndrome.

The ictal bradycardia syndrome is an uncommon diagnosis in which bradycardia is accompanied by simultaneous epileptic discharges in the EEG. We describe a patient who was referred to the emergency ward because of syncope. Ictal semeiology and EEG-EG findings are discussed and compared with those published in the literature. Therapeutic options are discussed in relation with those published in the literature. The ictal bradycardia syndrome is probably underdiagnosed, while its recognition is of utmost importance because of potential life threatening complications such as asystole. Up to now, its aetiology is poorly understood, its ictal semeiology is often described insufficiently and its therapy is still discussed.

Spinal cord stimulation in complex regional pain syndrome: cervical and lumbar devices are comparably effective.

BACKGROUND: Spinal cord stimulation (SCS) has been used since 1967 for the treatment of patients with chronic pain. However, long-term effects of this treatment have not been reported. The present study investigated the long-term effects of cervical and lumbar SCS in patients with complex regional pain syndrome type I. METHODS: Thirty-six patients with a definitive implant were included in this study. A pain diary was obtained from all patients before treatment and 6 months and 1 and 2 years after implantation. All patients were asked to complete a seven-point Global Perceived Effect (GPE) scale and the Euroqol-5D (EQ-5D) at each post-implant assessment point. RESULTS: The pain intensity was reduced at 6 months, 1 and 2 years after implantation (P<0.05). However, the repeated measures ANOVA showed a statistically significant, linear increase in the visual analogue scale score (P=0.03). According to the GPE, at least 42% of the cervical SCS patients and 47% of the lumbar SCS patients reported at least 'much improvement'. The health status of the patients, as measured on the EQ-5D, was improved after treatment (P<0.05). This improvement was noted both from the social and from the patients' perspective. Complications and adverse effects occurred in 64% of the patients and consisted mainly of technical defects. There were no differences between cervical and lumbar groups with regard to outcome measures. CONCLUSION: SCS reduced the pain intensity and improves health status in the majority of the CRPS I patients in this study. There was no difference in pain relief and complications between cervical and lumbar SCS.

Molecular studies on genetic integrity of open-pollinating species rye (Secale cereale L.) after long-term genebank maintenance.

The genetic integrity of six accessions represented by 14 sub-populations of the open-pollinating species rye ( Secale cereale L.) was investigated. Seeds available from a herbarium collection (first regeneration) and from the cold store (most recent regeneration) were multiplied two to fourteen times and fingerprinted using microsatellite markers. Four accessions had significantly different allele frequencies. These were multiplied seven to thirteen times. Nearly 50% of the alleles discovered in the original samples were not found in the material present in the cold store. However alleles were detected in the most recently propagated sub-populations, that were not observed in the investigated plants of the original one. The change in allele frequencies is a continuous process. Reasons for the occurrence of genetic changes and consequences for managing open pollinating species maintained in ex situ genebanks are discussed.

Sex-linked AFLP markers indicate a pseudoautosomal region in hemp ( Cannabis sativa L.).

In dioecious plants of hemp ( Cannabis sativa L.), males are regarded as heterogametic XY and females as homogametic XX, although it is difficult to discriminate the X cytologically from the Y. The Y chromosome is somewhat larger than the X. Our aim was to analyse AFLP markers on X and Y, and to use them to gain some insight into the structure of the sex chromosomes. Markers located on the sex chromosomes can be grouped into different classes, depending on the presence or absence of a fragment on the X and/or the Y. They are detected by separately analysing male and female progenies of a single cross. Five markers were found to be located on both chromosomes. A few recombinants were observed for marker pairs of this class in the male progenies. Two completely linked markers located on the Y chromosome in the male parent show a recombination rate of r = 0.25 with sex. Recombination must have occurred between the sex chromosomes in the male parent. The recombination analysis led to the conclusion that there is a pseudoautosomal region (PAR) on the sex chromosomes, allowing recombination between the X and the Y chromosome. The other regions of the sex chromosomes show only a few recombination events, for the Y as well as for the X. These results are discussed in comparison to other dioecious plants.

Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD).

Adults suffering from Attention Deficit Hyperactivity Disorder (ADHD) are known to have disturbed central dopaminergic transmission. With Single Photon Emission Computed Tomography (SPECT) we studied brain dopamine transporter and receptor activity in six boys with ADHD. Three months after initiation of treatment with methylphenidate we found a down-regulation of the post-synaptic dopamine receptor with a maximum of 20 % and a down-regulation of the dopamine transporter with a maximum of 74.7 % in the striatal system. This corresponded to a positive clinical response evaluated by neuropsychological questionnaires and tests. We suggest that dopamine transporter imaging by SPECT might be used to monitor psychostimulant treatment in children suffering from ADHD.

[Cerebral blindness]. / Cerebrale blindheid.

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.

Screening of patients with complex regional pain syndrome for antecedent infections.

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.

Pain catastrophizing predicts pain intensity, disability, and psychological distress independent of the level of physical impairment.

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.

[Pharmacotherapy for neuropathic pain caused by injury to the afferent nerve fibers]. / Farmacotherapie van neuropathische pijn door letsel van afferente zenuwvezels.

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.

Randomized controlled trial of percutaneous intradiscal radiofrequency thermocoagulation for chronic discogenic back pain: lack of effect from a 90-second 70 C lesion.

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.

Interobserver reliability in physical examination of the cervical spine in patients with headache.

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.

Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: retrospective analysis of clinical efficacy in 86 patients.

OBJECTIVE: Stellate ganglion (SG) blockade is used for the treatment of chronic pain syndromes in which the sympathetic nervous system is hypothesized to be involved. A possible treatment modality to achieve long-term pain reduction is blockade of the SG by means of a radiofrequency lesion (RF-SG). To evaluate the outcome of RF-SG as a therapy for different chronic pain syndromes, we reviewed 86 RF-SG procedures. DESIGN: Medical records containing treatment information were reviewed systematically. A systematic MEDLINE literature review search on SG blockade was also performed. RESULTS: In our clinic, 39.5% of 221 patients who received a prognostic SG block subsequently underwent RF-SG. Of these patients, 40.7% noted a more than 50% reduction of pain, 54.7% reported no effect on pain, and 4.7% showed worsening of pain. The mean follow-up interval was 52 weeks. The computer-assisted literature search resulted in 31 studies: 12 about complications and 19 about the efficacy of SG blockade. A review of these studies showed partial pain relief in 41.3% of patients, complete pain relief in 37.8%, and no pain relief in 20.9%. CONCLUSIONS: The efficacy of RF-SG blockade seems to be in line with that of other SG blockade procedures reported in the literature. Our retrospective study shows that an RF-SG block is most likely to be of benefit for patients suffering from complex regional pain syndrome type 2, ischemic pain, cervicobrachialgia, or postthoracotomy pain. Clinical efficacy remains to be proven in a randomized controlled trial, however.