The aim of the present study was to describe the occurrence of signs and symptoms in CRPS I patients meeting the IASP (Orlando) criteria, assess the occurrence of signs and symptoms in relation to... Show moreThe aim of the present study was to describe the occurrence of signs and symptoms in CRPS I patients meeting the IASP (Orlando) criteria, assess the occurrence of signs and symptoms in relation to disease duration and compare these to historical data based on a different diagnostic criteria set. Six hundred and ninety-two ambulatory patients meeting the IASP criteria for CRPS I referred to the outpatient clinics of five participating centers were included in this cross-sectional study. Characteristics were recorded in a standardized fashion and categorized according to the factor structure proposed by Bruehl/Harden. Subgroups were classified according to the duration of complaints and compared to historical data as described by Veldman et al. The Chi-square test corrected for multiple comparisons was used for statistical analysis. The prevalence of sensory signs was higher in patients with longer disease duration, especially for the allodynia's and hyperalgesia (all p <0.001). Signs in vasomotor (color difference; p =0.0007) and sudomotor (edema; p <0.0001) subgroups were less frequently present in patients with longer disease duration (i.e. >6 months). Prevalences of signs in the motor subgroup were all higher (p <0.0001) in patients with longer disease duration, except for limited range of motion. Occurrence of signs was significantly lower (<0.001) than those reported by Veldman et al., except for hyperesthesia and dystonia. Occurrence rates may vary at different time points after onset of CRPS, which may be of influence for diagnosing patients with novel derived diagnostic criteria. We argue for a mechanism based description of CRPS I based on one set of uniform generally accepted diagnostic criteria in future studies. Show less
About 25% of the patients with complex regional pain syndrome (CRPS) suffer movement disorders, including loss of voluntary control, bradykinesia, dystonia, myoclonus, and tremor. These movement... Show moreAbout 25% of the patients with complex regional pain syndrome (CRPS) suffer movement disorders, including loss of voluntary control, bradykinesia, dystonia, myoclonus, and tremor. These movement disorders are generally difficult to manage and add considerably to the disease burden. Over the last years, interesting findings have emerged that show how tissue or nerve injury may induce spinal plasticity (central sensitization), which alters sensory transmission and sensorimotor processing in the spinal cord and is associated with disinhibition. These changes, in turn, set the stage for the development of movement disorders seen in CRPS. There are no randomized control studies on the treatment of movement disorders in CRPS but findings from fundamental and clinical research suggest that strategies that enhance the central inhibitory state may benefit these patients. Show less
Groen, J.L.; Ritz, K.; Contarino, M.F.; Warrenburg, B.P. van de; Aramideh, M.; Foncke, E.M.; ... ; Tijssen, M.A. 2010
Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with... Show moreMutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio-cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult-onset >= 26 years) dystonia (n = 388) and early-onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early-onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult-onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult-onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech. (C) 2010 Movement Disorder Society Show less
Parkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The... Show moreParkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The aims of this study were to evaluate the frequency and clinical profile of RLS in a large cohort of PD patients. In 269 nondemented Caucasian PD patients, the four diagnostic criteria for RLS were administered by a RLS trained researcher. In patients with definite RLS, the severity of these symptoms was assessed. Furthermore, in all patients, relevant motor and nonmotor symptoms in PD were evaluated. Definite RLS was present in 11% of the patients. RLS patients were more often female (69% vs. 32%, P < 0.001), but no other significant differences existed between PD patients with and without RLS. Within the PD patients with RLS, severity of RLS correlated positively with PD severity, motor fluctuations, depressive symptoms, daytime sleepiness, cognitive problems, autonomic symptoms, and psychotic symptoms. This study in a large PD cohort shows that prevalence of RLS is similar to that in the general population, which might be caused by underestimation of RLS due to dopaminergic treatment. No relations were found between the presence of RLS and PD symptoms, but the severity of RLS was related to the severity of PD-related, mainly nondopaminergic, symptoms. It is hypothesized that, nondopaminergic systems, such as the noradrenergic system may play a role in the possible link between PD and RLS. (C) 2010 Movement Disorder Society Show less
Background: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder... Show moreBackground: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder. Both show clinical overlap with complex regional pain syndrome (CRPS), a condition that is characterized by pain in association with combinations of vasomotor, sudomotor, sensory, and motor disturbances. Therefore, we here investigated the involvement of the SCN9A gene in familial CRPS. Methods: We performed a mutation analysis of the SCN9A gene in four index cases of families with CRPS. All 26 coding exons and adjacent sequences of the SCN9A gene were analyzed for mutations using direct sequencing analysis. Results: No causal gene mutations were identified in the SCN9A gene in any of the patients. Conclusions: Despite the fact that the SCN9A gene is an excellent candidate, we did not find evidence that it plays a major role in familial CRPS. Show less
The clinical variability between patients with Parkinson's disease (PD) may point at the existence of subtypes of the disease. Identification of subtypes is important, since a focus on homogeneous... Show moreThe clinical variability between patients with Parkinson's disease (PD) may point at the existence of subtypes of the disease. Identification of subtypes is important, since a focus on homogeneous groups may enhance the chance of success of research on mechanisms of disease and may also lead to tailored treatment strategies. Cluster analysis (CA) is an objective method to classify patients into subtypes. We systematically reviewed the methodology and results of CA studies in PD to gain a better understanding of the robustness of identified subtypes. We found seven studies that fulfilled the inclusion criteria. Studies were limited by incomplete reporting and methodological limitations. Differences between studies rendered comparisons of the results difficult. However, it appeared that studies which applied a comparable design identified similar subtypes. The cluster profiles "old age-at-onset and rapid disease progression" and "young age-at-onset and slow disease progression" emerged from the majority of studies. Other cluster profiles were less consistent across studies. Future studies with a rigorous study design that is standardized with respect to the included variables, data processing, and CA technique may advance the knowledge on subtypes in PD. (C) 2010 Movement Disorder Society Show less
Rooij, A.M. de; Perez, R.S.G.M.; Huygen, F.J.; Eijs, F. van; Kleef, M. van; Bauer, M.C.R.; ... ; Marinus, J. 2010
Complex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly... Show moreComplex Regional Pain Syndrome (CRPS) usually develops after a noxious event, but spontaneous onsets have been described in 3-11% of the cases. The existence of spontaneous-onset CRPS is highly debated and the aim of the present study was therefore to compare the phenotypic characteristics of CRPS patients with a spontaneous onset, with those of patients with a trauma-induced onset. Data of 537 CRPS patients followed up at four departments of anesthesiology were analyzed and comprised 498 (93%) patients with and 39 (7%) patients without a known eliciting event. There where no significant differences between the two groups in gender, or in onset in upper or lower limb or left or right side of the body. Compared to CRPS patients with a trauma-induced onset, spontaneous-onset cases were on average 9 years younger at disease onset and had a 1.4 years longer median disease duration. No significant differences in frequency were found for any of the 34 compared signs and symptoms when the effect of multiple testing was controlled. In conclusion, CRPS may develop both with and without a precipitating noxious event, with both groups exhibiting a largely similar clinical presentation. Spontaneous-onset CRPS patients generally develop the syndrome at a younger age, possibly indicating a susceptibility to develop the condition. The longer disease duration in spontaneous-onset cases may reflect a more gradual disease onset, poorer prognosis, or a delay in diagnosis, possibly as a result of reluctance to make this diagnosis in the absence of a clear initiating event. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved. Show less
Munts, A.G.; Plas, A.A. van der; Ferrari, M.D.; Teepe-Twiss, I.M.; Marinus, J.; Hilten, J.J. van 2010
Activated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain, such as occurs in response to peripheral inflammation or tissue injury.... Show moreActivated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain, such as occurs in response to peripheral inflammation or tissue injury. Immune activation may therefore serve as a therapeutic target for immune modulating drugs like corticosteroids. This double-blind randomized placebo-controlled parallel-group trial aimed to investigate the efficacy and safety of a single intrathecal administration of 60 mg methylprednisolone (ITM) in chronic patients with complex regional pain syndrome (CRPS). The primary outcome measure was change in pain (pain intensity numeric rating scale; range 0-10) after 6 weeks. With 21 subjects per group the study had a 90% power to detect a clinically relevant difference (>= 2 points). After 21 patients (10 on ITM) were included, the trial was stopped prematurely after the interim analysis had shown that ITM had no effect on pain (difference in mean pain intensity numeric rating scale at 6 weeks 0.3, 95% confidence interval -0.7 to 1.3) or any other outcome measure. We did not find any difference in treatment-emergent adverse events between the ITM and placebo group. We conclude that a single bolus administration of ITM is not efficacious in chronic CRPS patients, which may indicate that spinal immune activation does not play an important role in this phase of the syndrome. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved. Show less
Gosso, M.F.; Rooij, A.M. de; Alsina-Sanchis, E.; Kamphorst, J.T.; Marinus, J.; Hilten, J.J. van; Maagdenberg, A.M.J.M. van den 2010
Complex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain... Show moreComplex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain poorly understood. Several genes (so-called DYT genes) identified in other causes of dystonia play a role in mechanisms that have been implicated in CRPS. Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS. Show less
Plas, A.A. van der; Rijn, M.A. van; Hilten, J.J. van 2010
