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Dive into the research topics where Erik M. Akkerman is active.

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Featured researches published by Erik M. Akkerman.


Neuropsychobiology | 2008

White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis

Bart D. Peters; Lieuwe de Haan; Nienke Dekker; Jorik Blaas; Hiske E. Becker; Peter Dingemans; Erik M. Akkerman; Charles B. L. M. Majoie; Therese van Amelsvoort; Gerard J. den Heeten; Don Linszen

There is increasing evidence of white matter pathology in schizophrenia. The aim of this study was to examine whether white matter abnormalities found with diffusion tensor imaging (DTI) in previous schizophrenia studies are present in the early phase of the illness. DTI was performed at 3 T on 10 male patients with a first (n = 8) or second (n = 2) psychotic episode of schizophrenia or schizoaffective disorder, 10 male patients at ultra-high risk of psychosis with (pre)psychotic symptoms and 10 healthy controls. Fibertracts found to be abnormal in other DTI studies (uncinate and arcuate fasciculus, anterior and dorsal cingulum, subdivisions of the corpus callosum) were calculated and visualized; tract-specific measurements (fractional anisotropy and trace) were performed. No differences were found between the healthy subjects and the 2 patient groups. These preliminary findings suggest that there is no white matter pathology of these association tracts detectable with DTI in the early stages of schizophrenic illness in males. Our findings are in contrast with DTI abnormalities found in some other first-episode studies. This discrepancy in findings may be related to differences in subject characteristics and DTI methodology. Possible effects of age, gender, level of education and illicit substance use on DTI findings in schizophrenia are discussed.


Psychiatry Research-neuroimaging | 2010

White matter connectivity and psychosis in ultra-high-risk subjects: A diffusion tensor fiber tracking study

Bart D. Peters; Peter Dingemans; Nienke Dekker; Jorik Blaas; Erik M. Akkerman; Therese van Amelsvoort; Charles B. L. M. Majoie; Gerard J. den Heeten; Don Linszen; Lieuwe de Haan

This study assessed with diffusion tensor imaging (DTI) whether ultra-high-risk subjects who later develop a psychotic disorder (UHR-P) show abnormalities in association white matter fiber tracts as compared to UHR subjects who do not convert to psychosis (UHR-NP) and healthy controls. Participants comprised 17 male UHR subjects and 10 male healthy controls, who received baseline DTI scans before clinical follow-up. The uncinate and arcuate fasciculi, anterior and dorsal cingulate, and subdivisions of the corpus callosum were calculated and visualized, and tract-specific measurements were performed. At 24-month follow-up seven UHR subjects had developed a first psychotic episode. Fractional anisotropy in baseline DTI scans, including left-right asymmetry measures, did not differ between the groups. Thus, DTI measures of these association white matter tracts were not biological markers of psychosis in our UHR sample. Abnormalities of these fiber tracts may develop around or after onset of psychosis. However, further DTI studies in UHR subjects are needed in larger samples.


Journal of Computer Assisted Tomography | 2002

Vertebra disc ratio as a parameter for bone marrow involvement and its application in Gaucher disease

Erik-Jan Vlieger; Mario Maas; Erik M. Akkerman; Carla E. M. Hollak; Gerard J. den Heeten

Objective To establish the vertebra disc ratio (VDR), the ratio of the average T1-weighted gray value of disc L3 and intervertebral disc L3/L4, as a parameter for bone marrow involvement. To explore its value as alternative for bone marrow fat fraction measured with Dixon Quantitative Chemical Shift Imaging (Ff) in Gaucher disease (GD). Methods Age dependency and normal value for the VDR were determined in 46 controls. The VDR in untreated GD (n = 22) and long-treated GD (7.5 years; n = 19) were compared with it. The changes in VDR in treated (n = 33) and untreated (n = 8) GD were calculated. The correlation between VDR and Ff was determined. Results Age dependency was small. The normal VDR was 1.90 ± 0.30, both untreated GD (1.29 ± 0.31) and long-treated GD (1.70 ± 0.33) differed significantly from normal. Changes in treated GD were significant in the first four treatment years, in untreated GD they were not. The correlation with Ff was 0.86. Conclusions The VDR is a useful parameter for evaluation of bone marrow of patients with GD. The VDR correlates very well with Ff, so applicability is expected in diseases in which Ff has proven to be useful.


PLOS ONE | 2013

Liver fibrosis in type I Gaucher disease: magnetic resonance imaging, transient elastography and parameters of iron storage.

Anneloes E. Bohte; Laura van Dussen; Erik M. Akkerman; Aart J. Nederveen; Ralph Sinkus; Peter L. M. Jansen; Jaap Stoker; Carla E. M. Hollak

Long term liver-related complications of type-1 Gaucher disease (GD), a lysosomal storage disorder, include fibrosis and an increased incidence of hepatocellular carcinoma. Splenectomy has been implicated as a risk factor for the development of liver pathology in GD. High ferritin concentrations are a feature of GD and iron storage in Gaucher cells has been described, but iron storage in the liver in relation to liver fibrosis has not been studied. Alternatively, iron storage in GD may be the result of iron supplementation therapy or regular blood transfusions in patients with severe cytopenia. In this pilot study, comprising 14 type-1 GD patients (7 splenectomized, 7 non-splenectomized) and 7 healthy controls, we demonstrate that liver stiffness values, measured by Transient Elastography and MR-Elastography, are significantly higher in splenectomized GD patients when compared with non-splenectomized GD patients (p = 0.03 and p = 0.01, respectively). Liver iron concentration was elevated (>60±30 µmol/g) in 4 GD patients of whom 3 were splenectomized. No relationship was found between liver stiffness and liver iron concentration. HFE gene mutations were more frequent in splenectomized (6/7) than in non-splenectomized (2/7) participants (p = 0.10). Liver disease appeared more advanced in splenectomized than in non-splenectomized patients. We hypothesize a relationship with excessive hepatic iron accumulation in splenectomized patients. We recommend that all splenectomized patients, especially those with evidence of substantial liver fibrosis undergo regular screening for HCC, according to current guidelines.


Blood Cells Molecules and Diseases | 2013

Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease

L. van Dussen; Ari Zimran; Erik M. Akkerman; Johannes M. F. G. Aerts; Milan Petakov; Deborah Elstein; Hanna Rosenbaum; David Aviezer; Einat Brill-Almon; Raul Chertkoff; Mario Maas; Carla E. M. Hollak

Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). As bone disease is one of the most debilitating features of GD, quantification of bone marrow involvement is important for monitoring the response to treatment. Therefore, bone marrow fat fraction (Ff) measured by quantitative chemical shift imaging (QCSI) was included as exploratory parameter to evaluate bone marrow response in treatment naïve GD patients participating in a double-blind, randomized phase III study. Eight GD patients with intact spleens were treated with 30 or 60U/kg biweekly. Ff results were compared to outcomes in 15 untreated Dutch GD patients with a follow-up interval of 1year. Five taliglucerase alfa treated patients had a Ff below the threshold that relates to complication risk (<0.23) at baseline (median (n=8) 0.19, range 0.11-0.35). Ff significantly increased compared to baseline (p=0.012) and compared to untreated patients (p=0.005), already after 1year of follow-up with further improvement up to 36months. In four patients with the lowest Ff, the higher dose resulted in increases above 0.23 within 1year. All patients had sustained improvements in all other parameters. There was no influence of antibodies on response parameters. Treatment with taliglucerase alfa results in significant increases in lumbar spine fat fractions, which indicates clearance of Gaucher cells from the bone marrow.


Journal of Bone and Mineral Research | 2015

Short-Term Effect of Estrogen on Human Bone Marrow Fat

E.J. Limonard; Annegreet Veldhuis-Vlug; Laura van Dussen; Jurgen H. Runge; Michael W. T. Tanck; Erik Endert; Annemieke C. Heijboer; Eric Fliers; Carla E. M. Hollak; Erik M. Akkerman; Peter H. Bisschop

Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, –0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17‐β estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17‐β estradiol administration (p < 0.001) and increased again after cessation. During 17‐β estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C‐terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17‐β estradiol rapidly reduces the marrow fat fraction, suggesting that 17‐β estradiol regulates bone marrow fat independent of bone mass.


Molecular Genetics and Metabolism | 2012

Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients

C. E. M. Hollak; E S de Sonnaville; David Cassiman; Gabor E. Linthorst; J. E. M. Groener; Eva Morava; R.A. Wevers; Marcel Mannens; Johannes M. F. G. Aerts; Wouter Meersseman; Erik M. Akkerman; Klaziena Niezen-Koning; M. F. Mulder; Gepke Visser; Frits A. Wijburg; Dirk J. Lefeber; Ben J. H. M. Poorthuis

Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement. In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease.


Haematologica | 2012

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes

Laura van Dussen; Timothy M. Cox; Erik Hendriks; Elizabeth M. Morris; Erik M. Akkerman; Mario Maas; Johanna E. M. Groener; Johannes M. F. G. Aerts; Patrick Deegan; Carla E. M. Hollak

This paper describes the effects of a switch to velaglucerase alfa in a group of adult patients with type 1 Gaucher disease, all of whom had previously had their dose reduced as a consequence of the worldwide imiglucerase shortage. Thirty-two patients from two large European Gaucher centers switched to treatment with velaglucerase alfa after 1-8.5 months of dose reduction. The course of important Gaucher disease parameters was studied at four time points: one year before the shortage, just before the shortage, before a switch to velaglucerase and after up to one year of treatment with velaglucerase. These parameters included hemoglobin concentration, platelet count, plasma chitotriosidase activity in all patients, and spleen and liver volumes (as well as bone marrow fat fraction images) in 10 patients. Decreases in platelet counts as a result of reduced treatment with imiglucerase were quickly restored on treatment with velaglucerase alfa. Chitotriosidase activity declined overall after switching. Five out of 10 patients had an increase in liver volume of at least 10% after six months of velaglucerase treatment, which was reversible in 3. Most patients received infusions at home and no important side effects were observed. Velaglucerase alfa appears to be a safe and effective alternative for imiglucerase.


Clinical Neurology and Neurosurgery | 2003

Epidermoid of the lateral ventricle: evaluation with diffusion-weighted and diffusion tensor imaging

Radboud W. Koot; Anuradha P. Jagtap; Erik M. Akkerman; Gerard J. den Heeten; Charles B. L. M. Majoie

We report of a large epidermoid tumor of the lateral ventricle in a 67-year-old man. Conventional imaging (CT, T1/T2, MRI) could not differentiate the tumor from the surrounding cerebral spinal fluid (CSF). On diffusion-weighted and diffusion anisotropy images the tumor was clearly seen as a hyperintense mass surrounded by hypointense CSF, highly suspected for epidermoid. Diffusion-tensor imaging (DTI) accentuated its lobulated structure and clearly demonstrated its relationship to neighboring white matter tracts. We suggest that in case of the suspicion of a space-occupying lesion in CSF containing areas, not distinguishable from CSF by conventional MR imaging, diffusion-weighted and diffusion-tensor MR imaging should be added.


American Journal of Neuroradiology | 2010

MR Spectroscopy Findings in Early Stages of Motor Neuron Disease

M.M. van der Graaff; Cristina Lavini; Erik M. Akkerman; Ch.B. Majoie; Aart J. Nederveen; Aeilko H. Zwinderman; F. Brugman; L. H. van den Berg; J.M.B.V. de Jong; M. de Visser

BACKGROUND AND PURPOSE: Upper motor neuron degeneration varies in different phenotypes of MND. We used single-voxel MR spectroscopy of the primary motor cortex to detect corticomotoneuron degeneration and glial hyperactivity in different phenotypes of MND with a relatively short disease duration, contributing to further delineation of the phenotypes. MATERIALS AND METHODS: We prospectively included patients with ALS-B, ALS-L, and PMA and compared their data with those of patients with PLS and healthy controls. Each cohort consisted of 12 individuals. Disease duration was <1 year in ALS and PMA, but longer in PLS by definition. Follow-up examination was at 6 months. We measured ALSFRS-R, finger- and foot-tapping speed, and levels of the following: 1) NAAx, 2) mIns, and 3) Glx in the primary motor cortex. RESULTS: At baseline, we found significantly decreased NAAx levels and increased mIns levels in PLS. Levels of NAAx and mIns in patients with ALS-L and ALS-B were not significantly different from those in controls, but NAAx levels were significantly lower compared with those in PMA. At follow-up, only in PMA was a decrease of NAAx demonstrated. Glx levels varied widely in all groups. Levels of NAAx and mIns correlated well with clinical variables. CONCLUSIONS: Metabolite changes suggest neuronal dysfunction and active glial involvement in PLS. The corticomotoneuron is affected in early ALS-B and ALS-L, but at a later stage also in PMA. MR spectroscopy data are useful to obtain insight into the disease process at the level of the upper motor neuron in various phenotypes of MND.

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Mario Maas

University of Amsterdam

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Jaap Stoker

University of Amsterdam

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