Risk of fracture in patients with Charcot-Marie-Tooth disease.

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.

Prevalence of pain in Parkinson's disease: a systematic review using the modified QUADAS tool.

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.

Neurologists' diagnostic accuracy of depression and cognitive problems in patients with parkinsonism.

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.

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients.

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.

Evaluation of editors' abilities to predict the citation potential of research manuscripts submitted to The BMJ: a cohort study.

OBJECTIVE: To evaluate the ability of The BMJ editors to predict the number of times submitted research manuscripts will be cited. DESIGN: Cohort study. SETTING: Manuscripts submitted to The BMJ, reviewed, and subsequently scheduled for discussion at a prepublication meeting between 27 August 2015 and 29 December 2016. PARTICIPANTS: 10 BMJ research team editors. MAIN OUTCOME MEASURES: Reviewed manuscripts were rated independently by attending editors for citation potential in the year of first publication plus the next year: no citations, below average (<10 citations), average (10-17 citations), or high (>17 citations). Predicted citations were subsequently compared with actual citations extracted from Web of Science (WOS). RESULTS: Of 534 manuscripts reviewed, 505 were published as full length articles (219 in The BMJ) by end of 2019 and indexed in WOS, 22 were unpublished, and one abstract was withdrawn. Among the 505 manuscripts, the median (IQR [range]) number of citations in the year of publication plus the following year was 9 (4-17 [0-150]); 277 (55%) manuscripts were cited <10 times, 105 (21%) were cited 10-17 times, and 123 (24%) cited >17 times. Manuscripts accepted by The BMJ were cited more highly (median 12 (IQR 7-24) citations) than those rejected (median 7 (3-12) citations). For all 10 editors, predicted ratings tended to increase in line with actual citations, but with considerable variation within categories; nine failed to identify the correct citation category for >50% (range 31%-52%) of manuscripts, and κ ranged between 0.01 to 0.19 for agreement between predicted and actual categories. Editors more often rated papers that achieved high actual citation counts as having low citation potential than the reverse. Collectively, the mean percentage of editors predicting the correct citation category was 43%, and for 160 (32%) manuscripts at least 50% of editors predicted the right category. CONCLUSIONS: Editors weren't good at estimating the citation potential of manuscripts individually or as a group; there is no wisdom of the crowd when it comes to BMJ editors.

The cross-sectional area of the vagus nerve is not reduced in Parkinson's disease patients.

Background: Recent studies have revealed the importance of the gut brain axis in the development of Parkinson's disease (PD). It has also been suggested that the cross-sectional area (CSA) of the vagus nerve can be used in the diagnosis of PD. Here, we hypothesize that the CSA of the vagus nerve is decreased in PD patients compared to control participants. Methods: In this study we measured the CSA of the vagus nerve on both sides in 31 patients with PD and 51 healthy controls at the level of the common carotid artery using high-resolution ultrasound. Results: The mean CSA of the left vagus nerve in the PD and the control group was respectively 2.10 and 1.90 and of the right respectively 2.54 and 2.24 mm2. There is no difference in CSA of the vagus nerve in PD patients compared to controls (p = .079). The mean CSA of the right vagus nerve was significantly larger than the left (p < .001). Age, sex and autonomic symptoms were no significant predictors of the CSA of the vagus nerve. Conclusion: These findings show that the CSA of the vagus nerve using ultrasonography is not a reliable diagnostic tool in the diagnosis of PD.

Clinical problems in the hospitalized Parkinson's disease patient: systematic review.

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.

Neuroanatomical correlates of apathy in Parkinson's disease: A magnetic resonance imaging study using voxel-based morphometry.

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.

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients.

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.

A systematic review of prevalence studies of depression in Parkinson's disease.

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.

The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans.

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.

Diagnostic value of 123I-ioflupane and 123I-iodobenzamide SPECT scans in 248 patients with parkinsonian syndromes.

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.

Meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes.

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.

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms.

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.

Randomised controlled trial of cervical radiofrequency lesions as a treatment for cervicogenic headache [ISRCTN07444684].

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.

An unusual case of posterior reversible encephalopathy syndrome in a patient being weaned from intrathecal morphine.

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.

Transcranial sonography findings related to depression in parkinsonian disorders: cross-sectional study in 126 patients.

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.

Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study.

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.

The joint contribution of physical pathology, pain-related fear and catastrophizing to chronic back pain disability.

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.

Dopamine transporter in attention-deficit hyperactivity disorder normalizes after cessation of methylphenidate.

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.