Search

Jasper Van Aalst,1 Onno P Teernstra,1 Wim E Weber,2 Kim Rijkers,31Department of Neurosurgery, 2Department of Neurology, Maastricht University Medical Center+, Maastricht, 3Department of Neurosurgery, Zuyderland Medical Center, Heerlen, the Netherlands Abstract: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity based on clinical signs, including headache, visual abnormalities, and seizures, and radiological abnormalities mostly consisting of vasogenic brain edema predominantly in the posterior parietal-temporal-occipital regions. PRES typically develops in the setting of a significant “systemic process”, including preeclampsia, transplantation, infection/sepsis/shock, autoimmune disease, and cancer chemotherapy, in which hypertension often plays an important role. We present a case of PRES in a 63-year-old female patient with an infected intrathecal morphine pump on a cocktail of antibiotics, morphine, clonidine, diazepam, and amitriptyline. It is the first PRES case in a chronic pain patient, which illustrates that PRES can occur in the absence of any of the established risk factors. We hypothesize it may have been caused by antibiotic treatment in our patient. Keywords: PRES, intrathecal morphine, neuropathic pain

Background. Transcranial sonography (TCS) has emerged as a potential diagnostic tool for Parkinson's disease. Recent research has suggested that abnormal echogenicity of substantia nigra, raphe nuclei and third ventricle is associated with increased risk of depression among these patients. We sought to reproduce these findings in an ongoing larger study of patients with parkinsonian syndromes. Methods. A total of 126 patients with parkinsonian symptoms underwent the Hamilton Depression Scale, and TCS of the substantia nigra (SN) (n = 126), the raphe nuclei (RN) (n = 80) and the third ventricle (n = 57). We then calculated the correlation between depression and hyper-echogenic SN, hypo-echogenic RN and a wider third ventricle. Results. In patients with PD we found no significant difference of the SN between non-depressed and depressed patients (46% vs. 22%; p = 0.18). Non-depressed patients with other parkinsonisms more often had hyperechogenicity of the SN than depressed patients (51% vs. 0%; p = 0.01). We found no relation between depression and the echogenicity of the RN or the width of the third ventricle. Conclusions. In patients with parkinsonian syndromes, we found no association between depression and hyper-echogenic SN, hypo-echogenic RN or a wider third ventricle, as determined by transcranial sonography.

Background. Patients with Parkinson's disease (PD) have a high risk of cognitive problems. Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism. Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson's disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up. Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems. Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies.

Introduction: In this study we evaluated fracture risk in patients with Charcot-Marie-Tooth (CMT) disease., Methods: We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with CMT disease was matched with up to 6 patients without a history of CMT disease. The outcome measure was fractures., Results: The risk of non-osteoporotic fracture was statistically significantly increased [adjusted hazard ratio (AHR) 1.47, 95% confidence interval (CI) 1.01-2.14], whereas risk of any and osteoporotic fracture did not reach statistical significance compared with control patients [AHR 1.31 (95% CI 0.98-1.74) and AHR 1.10 (95% CI 0.69-1.74), respectively]., Conclusions: CMT patients have a 1.5-fold increased risk for non-osteoporotic fracture. Studies with larger numbers of CMT patients and with additional data on CMT subtype, bone mineral density, and functional status should be performed to confirm a true association between CMT and an increased risk of fracture., (© 2014 Wiley Periodicals, Inc.)

Primary central nervous system (CNS) lymphoma is a rare form of non-Hodgkin's lymphoma. The clinical presentation is variable, depending on its localisation within the nervous system. Only 1% of primary CNS lymphoma emerges in the spinal cord, and the prevalence of primary lymphoma of the cauda equina is unknown, but probably even rarer. Diagnosing primary lymphoma of the cauda equina is difficult, since it can mimic other more common disorders such as a herniated disc, especially in its early stages. Here we present two cases of primary cauda equina lymphoma in which diagnostic work up took a long time, as the final diagnosis was only reached after a nerve root biopsy., (2014 BMJ Publishing Group Ltd.)

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.

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.

Background: Previous studies have shown that patients with Parkinson's disease (PD) are at increased risk of fractures. However, no specific prediction model for fracture estimation among PD patients is currently available. Therefore, the aim of this study was to develop a simple score for estimating the 5-year osteoporotic and hip fracture risks among patients with PD., Methods: The U.K. Clinical Practice Research Datalink (1987-2011) was used to identify incident PD patients. Cox proportional-hazards models were used to calculate the 5-year risks of osteoporotic and hip fracture among PD patients. The regression model was fitted with various risk factors for fracture and the final Cox model was converted into integer risk scores., Results: We identified 4411 incident PD patients without a history of osteoporotic treatment. The 5-year risks of osteoporotic and hip fracture were plotted in relation to the risk score. Risk scores increased with age, female gender, history of renal disease and history of dementia. The C-statistic, which is a parameter to test the internal validity of the model, was reasonable for the prediction of osteoporotic fracture (0.69) and hip fracture (0.73)., Conclusion: In this study, we developed a simple model to estimate 5-year fracture risk among incident PD patients. It may be useful in daily practice after external validation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Key Message: Our investigations combine chromosome 5A copy number variation associated with relative 5A Q gene expression and morphological and agronomic data to characterize the occurrence of speltoid plants in winter wheat cultivars. The occurrence of speltoid aberrants in wheat breeding is a serious problem that may result in rejection of a candidate cultivar during licensing. The spear-shaped, hard threshing spike is caused by copy number reduction of the domestication gene Q, located on the long arm of wheat chromosome 5A. As a member of the APETALA2-like transcription factor family, the 5AQ gene is involved in flower development and pleiotropically controls other agronomic traits. In this report, a characterization of instability of chromosome 5A is given and effects due to the loss of the Q gene and other genes are discussed. Based on pyrosequencing, we correctly predicted the 5AQ copy number for 392 of 402 tested offspring plants (97.5 %) originating from single speltoid plants of eleven wheat cultivars. The findings indicate that the resulting speltoid plants were either reduced in chromosome 5A copy number or possessed a partial deletion of the distal end of chromosome arm 5AL. 5AQ specific real-time PCR analysis revealed varying transcription levels among cultivars. During early spike development, the relative transcription of the 5AQ gene was always lower in speltoids than in normal square headed wheat plants, most likely leading to the occurrence of the characteristic speltoid spike phenotype. The parallel analysis of 18 agronomic traits revealed pleiotropic effects governed by genes located on 5A. Our results demonstrate that through pyrosequencing one can identify aneuploidy or deletions within chromosome 5A to select against the occurrence of speltoid plants in wheat seedlings.

Background: Retrospective studies suggest that many Parkinson's disease patients have a worsening of their motor status during hospitalization. We aimed to quantify this prospectively, and study possible contributing factors., Methods: Over one year we included all consecutive Parkinson's disease patients, newly admitted to a Dutch teaching hospital. We analyzed complications, interventions, and medication distribution. At inclusion and at discharge we assessed the motor status with the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)., Results: 48% of 46 admitted patients had complications, mainly confusion/delirium (24%) and infections (15%). At discharge 28% of the patients had a worse motor function with a mean increase of more than 5 points on the UPDRS-III. Medication errors occurred in 39%. This is the most important risk factor (p < 0.000) for motor function deterioration, followed by infections during hospitalization, and not being in control of own Parkinson's disease medication. 24% of patients were allowed to take control of their own Parkinson's disease medication, none of these patients did deteriorate., Conclusions: This prospective study shows that a substantial part of hospitalized PD patients has a significant worse motor function at discharge mainly due to medication errors and infections. Quality of care could be improved by addressing preventable errors and allow patients to take control of their own Parkinson's disease medication., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

Objective: Numerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated., Design: Prospective cohort study for diagnostic accuracy., Setting: Neurology outpatient clinics of two teaching hospitals in the Netherlands., Patients: 196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a (123)I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176)., Outcome Measures: After 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study., Results: Temporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84., Conclusions: The diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use. CLINICALTRIALS.GOV IDENTIFIER: NCT0036819.

Background: Depression and cognitive impairment (CI) are important non-motor symptoms in Parkinson's Disease (PD) and related syndromes, but it is not clear how well they are recognised in daily practice. We have studied the diagnostic performance of experienced neurologists on the topics depression and cognitive impairment during a routine encounter with a patient with recent-onset parkinsonian symptoms., Methods: Two experienced neurologists took the history and examined 104 patients with a recent-onset parkinsonian disorder, and assessed the presence of depression and cognitive impairment. On the same day, all patients underwent a Hamilton Depression Rating Scale test, and a Scales for Outcomes in Parkinson's Disease-Cognition-test (SCOPA-COG)., Results: The sensitivity of the neurologists for the topic depression was poor: 33.3%. However, the specificity varied from 90.8 to 94.7%. The patients' sensitivity was higher, although the specificity was lower. On the topic CI, the sensitivity of the neurologists was again low, in a range from 30.4 up to 34.8%: however the specificity was high, with 92.9%. The patients' sensitivity and specificity were both lower, compared to the number of the neurologists., Conclusions: Neurologists' intuition and clinical judgment alone are not accurate for detection of depression or cognitive impairment in patients with recent-onset parkinsonian symptoms because of low sensitivity despite of high specificity., Trial Registration: (ITRSCC)NCT0036819.

Pain has been studied more intensely as a symptom of Parkinson's disease (PD) in recent years. However, studies on the characteristics and prevalence of pain in PD have yielded conflicting results, prompting us to do a systematic review of the literature. A systematic review of the literature was conducted, using different databases. The last inclusion date was March 15, 2011. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used, which is especially designed for judging prevalence studies on their methodological quality. Only articles that met the predefined criteria were used in this review. We found 18 articles, of which only 8 met the methodological criteria. Prevalence frequency ranges from 40% to 85% with a mean of 67.6%. Pain is most frequently located in the lower limbs, with almost one-half of all PD patients complaining about musculoskeletal pain (46.4%). The pain fluctuates with on-off periods. Surprisingly, only 52.4% of PD patients with pain used analgesics, most often nonopioids. PD patients seem to be predisposed to develop pain and physicians should be aware of pain as a common feature of PD. As many as one-half of PD patients with pain may be missing out on a potentially useful treatment, and proper treatment could increase quality of life in PD patients., (Copyright © 2012 Movement Disorder Society.)

Background: A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards., Methods: We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed., Results: Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration., Conclusions: Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.

The problems Parkinson's disease (PD) patients encounter when admitted to a hospital, are known to be numerous and serious. These problems have been inventoried through a systematic review of literature on reasons for emergency and hospital admissions in PD patients, problems encountered during hospitalization, and possible solutions for the encountered problems using the Pubmed database. PD patients are hospitalized in frequencies ranging from 7 to 28% per year. PD/parkinsonism patients are approximately one and a half times more frequently and generally 2 to 14 days longer hospitalized than non-PD patients. Acute events occurring during hospitalization were mainly urinary infection, confusion, and pressure ulcers. Medication errors were also frequent adverse events. During and after surgery PD patients had an increased incidence of infections, confusion, falls, and decubitus, and 31% of patients was dissatisfied in the way their PD was managed. There are only two studies on medication continuation during surgery and one analyzing the effect of an early postoperative neurologic consultation, and numerous case reports, and opinionated views and reviews including other substitutes for dopaminergic medication intraoperatively. In conclusion, most studies were retrospective on small numbers of patients. The major clinical problems are injuries, infections, poor control of PD, and complications of PD treatment. There are many (un-researched) proposals for improvement. A substantial number of PD patients' admissions might be prevented. There should be guidelines concerning the hospitalized PD patients, with accent on early neurological consultation and team work between different specialities, and incorporating nonoral dopaminergic replacement therapy when necessary., (Copyright © 2011 Movement Disorder Society.)

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

Apathy is generally defined as a disorder of motivation and is considered one of the most common neuropsychiatric disturbances in Parkinson's disease (PD). Only few studies addressed the neuroanatomical correlates of apathy in PD. The aim of this article was to determine the structural correlates of apathy in PD patients. Fifty-five PD patients underwent a neuropsychiatric and neuropsychological examination, and a 3 T magnetic resonance imaging scan was acquired. A voxel-based multiple regression analysis was used to calculate correlation between gray matter density and severity measures of apathy. Apathy correlates with decreased cognitive functioning and more depressive symptoms but not with more severe motor symptoms. High apathy scores were correlated with low gray matter density values in a number of cortical brain areas: the bilateral precentral gyrus (BA 4, 6), the bilateral inferior parietal gyrus (BA 40), the bilateral inferior frontal gyrus (BA 44, 47), the bilateral insula (BA 13), the right (posterior) cingulate gyrus (BA 24, 30, 31), and the right precuneus (BA 31). Apathy in PD correlates with reduced gray matter density in a number of brain regions. The involvement of the cingulate gyrus and inferior frontal gyrus is in line with the results of earlier studies addressing apathy in patients with Alzheimer's disease or depressive disorder. Further studies addressing the pathogenesis of apathy are needed.

Background: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis., Methods: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care., Results: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options., Conclusion: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial.

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

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.

Objectives: The STAndards for Reporting studies of Diagnostic accuracy (STARD) for investigators and editors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) for reviewers and readers offer guidelines for the quality and reporting of test accuracy studies. These guidelines address and propose some solutions to two major threats to validity: spectrum bias and test review bias., Study Design and Setting: Using a clinical example, we demonstrate that these solutions fail and propose an alternative solution that concomitantly addresses both sources of bias. We also derive formulas that prove the generality of our arguments., Results: A logical extension of our ideas is to extend STARD item 23 by adding a requirement for multivariable statistical adjustment using information collected in QUADAS items 1, 2, and 12 and STARD items 3-5, 11, 15, and 18., Conclusion: We recommend reporting not only variation of diagnostic accuracy across subgroups (STARD item 23) but also the effects of the multivariable adjustments on test performance. We also suggest that the QUADAS be supplemented by an item addressing the appropriateness of statistical methods, in particular whether multivariable adjustments have been included in the analysis.

Background: Transcranial duplex scanning (TCD) of the substantia nigra (SN) is increasingly used to diagnose Idiopathic Parkinson's Disease (IPD). Up until now 70 diagnostic studies have been published, not only on investigation of the SN, but also of the lenticular nucleus (LN) and the Raphe nuclei (RN)., Method: We systematically reviewed all diagnostic TCD studies in parkinsonian patients up to June 2008., Results: We found 35 eligible studies. Of the 1534 IPD patients investigated in the 35 studies 200 (13%) had an inconclusive SN-TCD. An increased echo-intensity of the SN was seen in 1167 (87%) of the 1334 IPD patients, 276 (12%) of the 2340 healthy controls and in 41 (30%) of the 138 patients with an atypical parkinsonian syndrome (APS). On the contrary, a pathological LNTCD was found more often in APS patients (79%) than in IPD patients (23%) and healthy controls (6%). A decreased echo-intensity of the RN was found more often in depressed (46%) than in non-depressed IPD patients (16%)., Conclusions: SN-TCD accurately differentiates between patients with IPD and healthy controls, but not between patients with IPD and APS. LN-TCD is only moderate accurate to delineate IPD from APS, but combinations of SN- and LN-TCD may be more promising. RN-TCD has only marginal diagnostic accuracy in diagnosing depression in IPD and non-IPD patients. Before TCD can be implicated, more research is needed to standardize the TCD technique, to investigate the TCD in non-research settings and to determine the additional value of TCD compared with currently used clinical techniques like SPECT imaging.

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.

Background: Transcranial duplex sonography (TCD) of the substantia nigra has emerged as a promising, non-invasive tool to diagnose idiopathic Parkinson's disease (IPD). However, its diagnostic accuracy in patients with undefined parkinsonism remains to be determined. In this study we determined the predictive value of TCD for the clinical diagnosis in undiagnosed parkinsonian syndromes. Additionally we compared the predictive value of TCD with that of presynaptic and postsynaptic single photon emission computer tomography (SPECT) scans., Methods: We studied 82 patients with an unclassified parkinsonian syndrome. All 82 patients were subjected to a TCD, 59 of them underwent a presynaptic SPECT scans and 32 underwent a postsynaptic SPECT scan. We determined the diagnostic accuracy of TCD and SPECT scans in differentiating: 1) IPD patients from patients without nigrostriatal degeneration and 2) IPD patients from patients with atypical parkinsonian syndromes (APS). To compare the diagnostic accuracy of TCD and SPECT scans, we used the clinical diagnosis after follow-up according to generally accepted clinical criteria as the gold standard. This clinical diagnosis was determined by a movement disorder specialist. 3) Finally, we ascertained the predictive value of the TCD for the SPECT result., Results: The clinical diagnoses after follow-up resulted in 51 cases of IPD, 7 patients with APS and 17 patients without nigrostriatal degeneration. In total 7 patients remained undiagnosed. 1) The accuracy of TCD, assessed by sensitivity and specificity, to differentiate IPD patients from patients without nigrostriatal degeneration was 50% and 82% respectively. For the presynaptic SPECT scans sensitivity was 97% and specificity 100%. 2) In differentiating IPD patients from APS patients, the sensitivity and specificity of TCD was 50% and 43% respectively. For presynaptic SPECT scans this was 97% and 0%. For the postsynaptic SPECT scans the sensitivity was 75% and the specificity 81%. 3) The positive predictive value (PPV) of an abnormal TCD for an abnormal presynaptic SPECT scan was 88%., Conclusion: Presynaptic SPECT scanning has a higher predictive value for the clinical diagnosis than TCD. However, since the PPV of an abnormal TCD for parkinsonism with nigrostriatal degeneration is high, TCD might be used as screening tool, before ordering a presynaptic SPECT.

Prevalence rates of depressive disorders in Parkinson's disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinson's disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta-analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed., (2007 Movement Disorder Society)

Background: SPECT is one of the most employed techniques in the diagnostic workup of idiopathic Parkinson's disease (IPD). Despite its widespread use, the exact diagnostic accuracy of this technique in parkinsonian syndromes remains controversial., Methods: In this study, we investigated the diagnostic accuracy of an initial (123)I-ioflupane (FP-CIT) and/or (123)I-iodobenzamide (IBZM) SPECT to differentiate between IPD and other parkinsonian disorders. 248 patients underwent a SPECT scan because of an as yet unclassified parkinsonian syndrome in our clinic between 2001 and 2006. Gold standard was the clinical diagnosis derived from the latest available clinical record, or, when this was not possible, a new complete physical and neurological examination by a blinded movement disorder specialist neurologist. Mean follow-up between SPECT and the latest clinical information was 18 months (range 3 months to 5 years)., Results: 223 of the 248 patients were clinically definitely diagnosed after follow-up: IPD 127, atypical parkinsonian syndromes (APS) 27, essential tremor (ET) 22, vascular parkinsonism (VP) 16, drug-induced parkinsonism (DIP) 5, doubt between PD and APS 2, other diseases without dopaminergic involvement 24. The mean odds ratio (95% CI) for FP-CIT SPECT's ability to distinguish between IPD and ET was 82 (11-674); between IPD and VP 61 (8-490); between IPD and DIP 36 (2-697) and between IPD and APS was 1 (0-4). The odds ratio for the IBZM SPECT tracer to differentiate between IPD and APS was 7 (2-17)., Conclusions: FP-CIT SPECT is accurate to differentiate patients with IPD from those with ET, and IPD from VP and DIP. The accuracy of both FP-CIT and IBZM SPECT scans to differentiate between IPD and APS is low., ((c) 2008 S. Karger AG, Basel.)

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD. We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin., Methods/design: We will enroll 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain., Discussion: As this prospective trial enroll only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD., Methods: Relevant studies were searched in Medline, EMBASE and Cochrane databases with back-searching of their reference lists. We limited our analysis to studies with a clinically relevant methodology: i.e. when they assessed the ability of the SPECT to provide 1. diagnosis of PD in an early phase vs. normalcy; 2 diagnostic differentiation between PD and essential tremor (ET); 3. distinguishing between PD and vascular parkinsonism (VP); 4. delineation of PD from atypical parkinsonian syndromes (APS). Gold standard was, dependent on the study type, clinical examination at initial visit or follow-up, and/or response to dopaminergic agents., Results: The search gave 185 hits, of which we deemed 32 suitable for our analysis. From these we recalculated the diagnostic odds ratio of SPECT for the clinical questions above. The pooled odds ratio (with 95%CI) for presynaptic SPECT scan's ability to distinguish between early PD and normalcy was 60 (13 - 277). For the ability to differentiate between PD and ET this ratio was 210 (79-562). The ratio for presynaptic SPECT's ability to delineate PD from VP was 105 (32 - 348). The mean odds ratio for the presynaptic SPECT scans to differentiate between PD and the two APS was 2 (1 - 4), and for the postsynaptic SPECT imaging this was 19 (9-36)., Conclusion: SPECT with presynaptic radiotracers is relatively accurate to differentiate patients with PD in an early phase from normalcy, patients with PD from those with ET, and PD from VP. The accuracy of SPECT with both presynaptic and postsynaptic tracers to differentiate between PD and APS is relatively low.

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.

Background and Aims: Germination and establishment of seeds are complex traits affected by a wide range of internal and external influences. The effects of parental temperature preconditioning and temperature during germination on germination and establishment of Arabidopsis thaliana were examined., Methods: Seeds from parental plants grown at 14 and at 22 degrees C were screened for germination (protrusion of radicle) and establishment (greening of cotyledons) at three different temperatures (10, 18 and 26 degrees C). Seventy-three accessions from across the entire distribution range of A. thaliana were included., Key Results: Multifactorial analyses of variances revealed significant differences in the effects of genotypes, preconditioning, temperature treatment, and their interactions on duration of germination and establishment. Reaction norms showed an enormous range of plasticity among the preconditioning and different germination temperatures. Correlations of percentage total germination and establishment after 38 d with the geographical origin of accessions were only significant for 14 degrees C preconditioning but not for 22 degrees C preconditioning. Correlations with temperature and precipitation on the origin of the accessions were mainly found at the lower germination temperatures (10 and 18 degrees C) and were absent at higher germination temperatures (26 degrees C)., Conclusions: Overall, the data show huge variation of germination and establishment among natural accessions of A. thaliana and might serve as a valuable source for further germination and plasticity studies.

Background: Cervicogenic headache (CEH) is a unilateral headache localised in the neck or occipital region, projecting to the frontal and temporal regions. Since the pathogenesis of this syndrome appears to have an anatomical basis in the cervical region, several surgical procedures aimed at reducing the nociceptive input on the cervical level, have been tested. We developed a sequence of various cervical radiofrequency neurotomies (facet joint denervations eventually followed by upper dorsal root ganglion neurotomies) that proved successful in a prospective pilot trial with 15 CEH patients. To further evaluate this sequential treatment program we conducted a randomised controlled trial, Methods: 30 patients with cervicogenic headache according to the Sjaastad diagnostic criteria, were randomised. 15 patients received a sequence of radiofrequency treatments (cervical facet joint denervation, followed by cervical dorsal root ganglion lesions when necessary), and the other 15 patients underwent local injections with steroid and anaesthetic at the greater occipital nerve, followed by transcutaneous electrical nerve stimulation (TENS) when necessary. Visual analogue scores for pain, global perceived effects scores, quality of life scores were assessed at 8, 16, 24 and 48 weeks. Patients also kept a headache diary., Results: There were no statistically significant differences between the two treatment groups at any time point in the trial., Conclusion: We did not find evidence that radiofrequency treatment of cervical facet joints and upper dorsal root ganglions is a better treatment than the infiltration of the greater occipital nerve, followed by TENS for patients fulfilling the clinical criteria of cervicogenic headache.

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder of childhood, which is frequently treated with methylphenidate. The short-term response to treatment with methylphenidate is a substantial decrease in dopamine transporter density, with improvement in neuropsychological tests. In this study, single-photon emission computed tomography was used to investigate possible long-term alterations in the cerebral dopamine system after cessation of treatment with methylphenidate in five children with ADHD. Three months after initiation of treatment with methylphenidate, a reduction of the dopamine transporter in the striatal system was observed. Methylphenidate was administered for a period of 9 to 20 months. Follow-up with single-photon emission computed tomography after withdrawal of methylphenidate medication disclosed an increase of dopamine transporter activity comparable with pretreatment values. The observed upregulation of dopamine transporter activity might support the assumption that methylphenidate does not lead to permanent damage of the nigrostriatal dopaminergic pathways.

The present study examined the contribution of physical pathology, pain-related fear and catastrophizing cognitions to pain intensity and disability in 100 patients with non-specific low back pain. Self-report instruments were completed as part of the intake procedure of patients, while physical pathology was quantified from medical charts using the MEDICS procedure. Results of the multiple regression analyses, adjusted for relevant demographic variables, pain intensity and pain duration, indicated that physical pathology was associated with pain intensity, but not with self-reported physical disability. Disability showed the strongest association with pain intensity. However, pain-related fear and catastrophizing contributed 4-10% additional explained variance to the regression models for pain intensity and disability. Thus, this study confirms the relationship between biological and psychological variables in determining the severity of low back pain complaints, and underscores the necessity for a multidisciplinary approach to diagnostics and intervention.

Background: Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I., Methods: We did a randomized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period. Patients started at random with gabapentin or placebo, which was administered in identical capsules three times daily. We included 58 patients with CRPS type 1., Results: Patients reported significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less; finally resulting in no significant effect combining results of both periods. The CRPS patients had sensory deficits at baseline. We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users., Conclusions: Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin.

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.

Objective: To establish the health-related quality of life of patients with cervicogenic headache and to compare it with a random Dutch sample of control subjects and with patients with migraine without aura or with episodic tension-type headache., Methods: Thirty-seven patients with cervicogenic headache, 42 patients with episodic tension-type headache, and 39 patients with migraine without aura completed a Medical Outcomes Study 36-Item Short Form questionnaire., Results: Domain scores for "physical functioning" of patients with cervicogenic headache were worse than those of patients with migraine or tension-type headache. Physical functioning scores were lower for patients with tension-type headache than for those with migraine. Migraineurs reported a diminished score for "social functioning" compared to patients with tension-type headache. All Medical Outcomes Study 36-Item Short Form domain scores were significantly lower for patients with cervicogenic headache relative to the control group., Conclusions: Patients with cervicogenic headache have a quality of life burden that is substantial. Although impairment in the quality of life of patients with cervicogenic headache is comparable to patients with migraine without aura and those with episodic tension-type headache, there are some specific differences.

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.

Objective: To investigate the degree of pain reduction in patients with complex regional pain syndrome type 1 (CRPS 1) that can be defined as "successful.", Design: All patients rated their pain on a visual analog scale (VAS; 0-10) before treatment and on three occasions after treatment, at 6 months, 1 year, and 2 years. Patients also rated a Global Perceived Effect (GPE) for their pain relief at the same time periods. The GPE items were classified as "successful" or "unsuccessful." The mean absolute and relative pain reduction (using the VAS) was calculated for both "successful" and "unsuccessful" GPE classifications for each time period. Sensitivity and specificity analyses were performed., Patients: Sixty-one patients with CRPS 1., Results: The patients defined a relative pain reduction of 58% (SD, 23.4) or more as "successful," whereas in "successful" and "unsuccessful" patient groups the pain was reduced significantly on the VAS. Furthermore, sensitivity and specificity analyses showed that a cut-off point of 50% relative pain reduction and a 3-cm absolute pain reduction on the VAS have the highest likelihood that patients will report their treatment "successful" on the GPE., Conclusions: Relative pain reduction of 50% or more and an absolute pain reduction of at least 3 cm on the VAS are accurate in predicting a successful pain reduction after a given treatment.

Because of its unpredictable clinical course, treatment strategies for low-grade (grade II) astrocytoma vary from "wait and see" to gross tumour resection followed by immediate radiotherapy. Clinical studies on grade II astrocytoma show that 5-year-survival ranges from 27% to 85% of patients with very few consistent prognostic variables besides the patient's age and the presence of neurological deficit. There is no universally recognised choice of therapy for patients with astrocytoma grade II, partly because of the shortcomings of histological classification systems. Routine microscopy tends to underestimate malignancy grading of astrocytomas and in most cases cannot distinguish between indolent and progressive subtypes. Recent studies suggest that proliferation and genetic markers can be used to identify subgroups of astrocytoma grade II with a rapid progressive clinical course. Therefore these markers should be included in ongoing and future clinical studies of patients with astrocytoma grade II.

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.

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.

Complex regional pain syndrome type I (CRPS-I), formerly reflex sympathetic dystrophy (RSD), is a chronic pain syndrome of unknown aetiology. Its diagnosis is a clinical one, for which several criteria systems have been defined. Despite their widespread use, the reliability of these criteria has never been studied. In this interobserver study 25 chronic CRPS patients were interviewed and examined by six physicians. Through structured questionnaires signs, symptoms, and diagnosis were recorded, after which observer agreement for these was calculated with kappa statistics. Physicians' agreement in assessment of signs and symptoms in CRPS patients varied greatly. More importantly, final diagnosis of CRPS showed poor observer agreement (kappa: 0.20). The kappa values were higher, had physicians applied IASP criteria, but still insufficient. The application of Bruehl's criteria results in a fair kappa of 0.38, but then frequency of CRPS diagnosis in our study population decreased from 73% to 43% in comparison with physicians' own diagnosis. We conclude that, using current criteria systems, the diagnosis of CRPS is not reliable.