Epidemiology of chronic inflammatory demyelinating polyradiculoneuropathy in The Netherlands

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare but disabling disorder that often requires long‐term immunomodulatory treatment. Background incidence rates and prevalence and risk factors for developing CIDP are still poorly defined. In the current study, we used a longitudinal population‐based cohort study in The Netherlands to assess these rates and demographic factors and comorbidity associated with CIDP. We determined the incidence rate and prevalence of CIDP between 2008 and 2017 and the occurrence of potential risk factors in a retrospective Dutch cohort study using the Integrated Primary Care Information (IPCI) database. Cases were defined as CIDP if the diagnosis of CIDP was described in the electronic medical file. In a source population of 928 030 persons with a contributing follow‐up of 3 525 686 person‐years, we identified 65 patients diagnosed with CIDP. The overall incidence rate was 0.68 per 100 000 person‐years (95% CI 0.45‐0.99). The overall prevalence was 7.00 per 100 000 individuals (95% CI 5.41‐8.93). The overall incidence rate was higher in men compared to woman (IRR 3.00, 95% CI 1.27‐7.11), and higher in elderly of 50 years or older compared with people <50 years of age (IRR 17 95% CI 4‐73). Twenty percent of CIDP cases had DM and 9% a co‐existing other auto‐immune disease. These background rates are important to monitor changes in the frequency of CIDP following infectious disease outbreaks, identify potential risk factors, and to estimate the social and economic burden of CIDP

Evaluation of management and guideline adherence in children with mild traumatic brain injury

Aim: To evaluate the management and guideline adherence in children with mild traumatic brain injury (MTBI) in emergency departments (ED) in the Netherlands. Methods: A multicentre cohort study was conducted, including children younger than 18 years with MTBI who presented within 24 hours after trauma in the ED of hospitals in the southwest region of the Netherlands, in 2014. Primary outcome measures for management were percentages of performed computed tomography (CT) scans and hospital admissions. Guideline adherence was defined as percentages of correctly following the guideline. Secondary outcome measures were differences in management and guideline adherence between hospitals. Results: About 563 patients were analysed. Hospital admission was the most frequently performed management type (49.2% hospital admission vs. 30.9% CT). In only 49.7% of patients, the guideline was followed correctly. A substantial overuse of hospital admission (35%) and underuse of CT (40.1%) were found. Percentages of hospital admission and CT varied between 39.4–55.6% and 23.3–44.1%, respectively, across hospitals. Percentages of correctly following the guideline varied between 39.2–64.9% across hospitals. Conclusion: These findings suggest that physicians in the participating hospitals prefer hospital admission of children with MTBI instead of CT despite the current recommendations of the national MTBI guideline in the Netherlands

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. In

George Romney, Education in Michigan, 1964

George Romney (July 8, 1907 – July 26, 1995) was an American businessman and Republican Party politician. He was chairman and president of AmericanMotorsCorporation from 1954 to 1962, the 43rd Governor of Michigan from 1963 to 1969, and the United States Secretary of Housing and Urban Development from 1969 to 1973. He was the father of 2003–07 Governor of Massachusetts and 2012 Republican presidential nominee Mitt Romney and the husband of 1970 U.S. Senate candidate Lenore Romney. In this address, given inside Pease Auditorium on the campus of Eastern Michigan University, Romney discusses the current state of public and private education in Michigan, claiming that education is the number one industry in the nation, and that Michigan has a monopoly on the production of good teachers and schools.https://commons.emich.edu/lectures_presentations/1004/thumbnail.jp

Misdiagnosis and diagnostic pitfalls of chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: The aim of this study was to determine the frequency of over- and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls. Methods: We conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups. Results: A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level. Conclusion: Over- and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy

Misdiagnosis and diagnostic pitfalls of chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: The aim of this study was to determine the frequency of over- and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls. Methods: We conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups. Results: A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level. Conclusion: Over- and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy

The Role of Lamins in the Nucleoplasmic Reticulum, a Pleiomorphic Organelle That Enhances Nucleo-Cytoplasmic Interplay

Invaginations of the nuclear membrane occur in different shapes, sizes, and compositions. Part of these pleiomorphic invaginations make up the nucleoplasmic reticulum (NR), while others are merely nuclear folds. We define the NR as tubular invaginations consisting of either both the inner and outer nuclear membrane, or only the inner nuclear membrane. Specifically, invaginations of both the inner and outer nuclear membrane are also called type II NR, while those of only the inner nuclear membrane are defined as type I NR. The formation and structure of the NR is determined by proteins associated to the nuclear membrane, which induce a high membrane curvature leading to tubular invaginations. Here we review and discuss the current knowledge of nuclear invaginations and the NR in particular. An increase in tubular invaginations of the nuclear envelope is associated with several pathologies, such as laminopathies, cancer, (reversible) heart failure, and Alzheimer’s disease. Furthermore, viruses can induce both type I and II NR. In laminopathies, the amount of A-type lamins throughout the nucleus is generally decreased or the organization of lamins or lamin-associated proteins is disturbed. Also, lamin overexpression or modulation of lamin farnesylation status impacts NR formation, confirming the importance of lamin processing in NR formation. Virus infections reorganize the nuclear lamina via (de)phosphorylation of lamins, leading to an uneven thickness of the nuclear lamina and in turn lobulation of the nuclear membrane and the formation of invaginations of the inner nuclear membrane. Since most studies on the NR have been performed with cell cultures, we present additional proof for the existence of these structures in vivo, focusing on a variety of differentiated cardiovascular and hematopoietic cells. Furthermore, we substantiate the knowledge of the lamin composition of the NR by super-resolution images of the lamin A/C and B1 organization. Finally, we further highlight the essential role of lamins in NR formation by demonstrating that (over)expression of lamins can induce aberrant NR structures

The Role of Lamins in the Nucleoplasmic Reticulum, a Pleiomorphic Organelle That Enhances Nucleo-Cytoplasmic Interplay

Invaginations of the nuclear membrane occur in different shapes, sizes, and compositions. Part of these pleiomorphic invaginations make up the nucleoplasmic reticulum (NR), while others are merely nuclear folds. We define the NR as tubular invaginations consisting of either both the inner and outer nuclear membrane, or only the inner nuclear membrane. Specifically, invaginations of both the inner and outer nuclear membrane are also called type II NR, while those of only the inner nuclear membrane are defined as type I NR. The formation and structure of the NR is determined by proteins associated to the nuclear membrane, which induce a high membrane curvature leading to tubular invaginations. Here we review and discuss the current knowledge of nuclear invaginations and the NR in particular. An increase in tubular invaginations of the nuclear envelope is associated with several pathologies, such as laminopathies, cancer, (reversible) heart failure, and Alzheimer's disease. Furthermore, viruses can induce both type I and II NR. In laminopathies, the amount of A-type lamins throughout the nucleus is generally decreased or the organization of lamins or lamin-associated proteins is disturbed. Also, lamin overexpression or modulation of lamin farnesylation status impacts NR formation, confirming the importance of lamin processing in NR formation. Virus infections reorganize the nuclear lamina via (de)phosphorylation of lamins, leading to an uneven thickness of the nuclear lamina and in turn lobulation of the nuclear membrane and the formation of invaginations of the inner nuclear membrane. Since most studies on the NR have been performed with cell cultures, we present additional proof for the existence of these structures in vivo, focusing on a variety of differentiated cardiovascular and hematopoietic cells. Furthermore, we substantiate the knowledge of the lamin composition of the NR by super-resolution images of the lamin A/C and B1 organization. Finally, we further highlight the essential role of lamins in NR formation by demonstrating that (over)expression of lamins can induce aberrant NR structures

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice. Methods: We investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by ≥1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes. Results: In univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6–30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13–0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67). Conclusions: Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP