Peter van Domburg - Academia.edu (original) (raw)
Papers by Peter van Domburg
![Research paper thumbnail of Added diagnostic accuracy after [18F]flutemetamol PET scanning in young patients with dementia in an academic memory clinic setting](https://attachments.academia-assets.com/112119487/thumbnails/1.jpg)
](medRxiv (Cold Spring Harbor Laboratory), Dec 3, 2021
Below we provide a draft description of results of one of the research questions as set in the Fl... more Below we provide a draft description of results of one of the research questions as set in the Flutemetamol study (trial registry link https://www.clinicaltrialsregister.eu/ctrsearch/trial/2012-002303-18/NL). During the project the validity of the method was discussed, in light of the swiftly developing state of the art in the field. After consultation of an external expert* the decision was made not to finalize the manuscript and refrain from submitting the work to a journal.
American Journal of Neuroradiology, Apr 1, 2004
Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency... more Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency in lipid metabolism. Our purpose was to characterize the nature of the cerebral involvement in SLS. METHODS: MR imaging was performed in 18 patients (aged 5 months to 45 years) and repeated in 14. Single-voxel proton MR spectra were acquired from cerebral white matter and gray matter in 16 patients, with follow-up studies in 11. LCModel fits were used to determine brain metabolite levels. RESULTS: MR imaging showed retardation of myelination and a mild persistent myelin deficit. A zone of increased signal intensity was seen in the periventricular white matter on T2-weighted images. Proton MR spectroscopy of white matter revealed a prominent peak at 1.3 ppm, normal levels of N-acetylaspartate, and elevated levels of creatine (؉14%), choline (؉18%), and myo-inositol (؉54%). MR imaging and proton MR spectroscopy of gray matter were normal. In the two patients examined during the first years of life, abnormalities on MR imaging and proton MR spectroscopy gradually emerged and then stabilized, as in all other patients. CONCLUSION: Abnormalities on MR imaging and proton MR spectroscopy emerge during the first years of life and are similar in all patients with SLS, but the severity varies. The changes are confined to cerebral white matter and suggest an accumulation of lipids, periventricular gliosis, delayed myelination, and a mild permanent myelin deficit. Sjögren-Larsson syndrome (SLS, OMIM 270200) is an inborn error of fatty alcohol oxidation with an autosomal recessive mode of inheritance. The wellknown clinical triad includes ichthyosis, spastic diplegia or tetraplegia, and mental retardation (1). The congenital ichthyosis usually brings the patient to medical attention, whereas spasticity and mental retardation become apparent later in the first or second year of life. Preterm birth, pruritus, and ocular abnormalities (including a juvenile macular dystrophy) occur in most cases (2-6).
American Journal of Ophthalmology, Dec 1, 2000
To report the ocular manifestations associated with the Sjögren-Larsson syndrome in a series of p... more To report the ocular manifestations associated with the Sjögren-Larsson syndrome in a series of patients with proven fatty aldehyde dehydrogenase deficiency. To emphasize the clinical importance of the ophthalmological features of the Sjögren-Larsson syndrome. To discuss the metabolic disturbances that might give rise to the ophthalmological picture. Fifteen patients with Sjögren-Larsson syndrome underwent a standardized ophthalmological examination. In patients of appropriate age, and who were able to cooperate, additional investigations were performed. All patients exhibited bilateral, glistening yellow-white crystalline deposits that were located in the innermost retinal layers and appeared during the first 2 years of life. Repeated fundus photography in individual patients showed that the dots became more numerous as the patients got older. Photophobia, subnormal visual acuity, myopia, and astigmatism were found in most of the patients. Fluorescein angiography was performed in three patients and showed a mottled hyperfluorescence of the retinal pigment epithelium, without leakage. Color vision, electroretinography, and electro-oculography could be performed in only a small number of patients and showed no abnormalities. Visual evoked potentials were found to be abnormal in six of eight patients. In Sjögren-Larsson syndrome, patients exhibit highly characteristic bilateral, glistening yellow-white retinal dots from the age of 1 to 2 years onward. The number of dots increases with age. The extent of the macular abnormality does not correlate with the severity of the ichthyosis or with the severity of the neurological abnormalities. A high percentage of patients shows additional ocular signs and symptoms, notably marked photophobia.
Journal of the Neurological Sciences, Sep 1, 2012
In Parkinson&... more In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.
Brain, Jul 1, 2001
Sjögren-Larsson syndrome (SLS) is an autosomal recessively inherited neurocutaneous disorder caus... more Sjögren-Larsson syndrome (SLS) is an autosomal recessively inherited neurocutaneous disorder caused by a deficiency of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH). We report the clinical characteristics and the results of molecular studies in 19 SLS patients. Patients 1-17 show the classical triad of severe clinical abnormalities including ichthyosis, mental retardation and spasticity. Most patients were born preterm, and all patients exhibit ocular abnormalities and pruritus. Electro-encephalography shows a slow background activity, without other abnormalities. MRI of the brain shows an arrest of myelination, periventricular signal abnormalities of white matter and mild ventricular enlargement. Cerebral 1 H-MR spectroscopy reveals a characteristic, abnormal lipid peak. The degree of white matter abnormality in the MRIs and the height of the lipid peak in 1 H-MR spectra do not correlate with the
JIMD reports, Mar 25, 2020
Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused... more Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype-phenotype correlation nor an alternative explanation for the
Neurology, Apr 1, 1999
Objective: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty a... more Objective: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty aldehyde dehydrogenase (FALDH) deficiency. Background: The Sjögren–Larsson syndrome (SLS) was originally defined as a clinical triad consisting of ichthyosis, spastic di- or tetraplegia, and mental retardation, with autosomal recessive inheritance. By now, both the deficiency of the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome. Methods: The clinical findings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to 1H MRS in six patients. Results: The severity of neurologic symptoms showed considerable variation. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidence of retarded myelination and a variable degree of dysmyelination. 1H MRS showed an accumulation of free lipids in the periventricular white matter, even before the stage of visible dysmyelination. Conclusions: The neurologic consequences of FALDH deficiency show considerable variation. The characteristic pattern of ichthyosis and retinal degeneration are seen consistently, yet they are not pathognomonic. MRI and 1H MRS findings suggest an accumulation of long-chain fatty alcohol intermediates, resulting in retarded myelination and dysmyelination.
Item does not contain fulltex
Springer eBooks, 1991
Although it has been known for many years that various disturbances of movement and posture are a... more Although it has been known for many years that various disturbances of movement and posture are associated with lesions in one or another of the basal ganglia (e.g., Wilson 1914; Denny-Brown 1960, 1962; Denny-Brown and Yanagisawa 1976; DeLong and Georgopoulos 1981), it is still not possible to account for individual symptoms, such as tremor, rigidity, or athetosis, in terms of normal or abnormal functioning of a particular component of the basal ganglia. Tremor cannot be produced in animals by lesions limited to structures of the basal ganglia. Neither electrolytic lesions of the SN nor 6-hydroxydopamine (6-OHDA) lesions of the ascending DAergic pathways from the SN and adjacent VTA produced tremor (Poirier 1960; DeLong and Georgopoulos 1981). It is only when lesions of the ascending cerebellar efferents are combined with nigrostriatal lesions that tremor appears. The usual site at which lesions are placed is in the VTA of the midbrain. Here, the lesions interrupt several pathways involving the SN and red nucleus: nigrostriatal, cerebellorubral, cerebellothalamic, and rubroolivary tracts. The conclusion is that parkinsonian rest tremor is not due to a purely striatal DA deficiency, but that damage to other structures, particularly the cerebellorubrothalamic projections, must also be involved. The ventrolateral thalamic nucleus has long been known to be involved in tremor generation (see I.S. Cooper et al. 1968). Hypokinesia and rigidity, cardinal features in Parkinson’s disease, are hypothesized to result from a complex series of changes resulting in an increase in basal ganglia output, particularly to the ventrolateral thalamic nucleus (DeLong and Georgopoulos 1981; Albin et al. 1989).
Journal of Alzheimer's Disease, Nov 19, 2016
People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:
Annals of Neurology, Aug 1, 2009
medRxiv (Cold Spring Harbor Laboratory), Dec 3, 2021
Below we provide a draft description of results of one of the research questions as set in the Fl... more Below we provide a draft description of results of one of the research questions as set in the Flutemetamol study (trial registry link https://www.clinicaltrialsregister.eu/ctrsearch/trial/2012-002303-18/NL). During the project the validity of the method was discussed, in light of the swiftly developing state of the art in the field. After consultation of an external expert* the decision was made not to finalize the manuscript and refrain from submitting the work to a journal.
American Journal of Neuroradiology, Apr 1, 2004
Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency... more Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency in lipid metabolism. Our purpose was to characterize the nature of the cerebral involvement in SLS. METHODS: MR imaging was performed in 18 patients (aged 5 months to 45 years) and repeated in 14. Single-voxel proton MR spectra were acquired from cerebral white matter and gray matter in 16 patients, with follow-up studies in 11. LCModel fits were used to determine brain metabolite levels. RESULTS: MR imaging showed retardation of myelination and a mild persistent myelin deficit. A zone of increased signal intensity was seen in the periventricular white matter on T2-weighted images. Proton MR spectroscopy of white matter revealed a prominent peak at 1.3 ppm, normal levels of N-acetylaspartate, and elevated levels of creatine (؉14%), choline (؉18%), and myo-inositol (؉54%). MR imaging and proton MR spectroscopy of gray matter were normal. In the two patients examined during the first years of life, abnormalities on MR imaging and proton MR spectroscopy gradually emerged and then stabilized, as in all other patients. CONCLUSION: Abnormalities on MR imaging and proton MR spectroscopy emerge during the first years of life and are similar in all patients with SLS, but the severity varies. The changes are confined to cerebral white matter and suggest an accumulation of lipids, periventricular gliosis, delayed myelination, and a mild permanent myelin deficit. Sjögren-Larsson syndrome (SLS, OMIM 270200) is an inborn error of fatty alcohol oxidation with an autosomal recessive mode of inheritance. The wellknown clinical triad includes ichthyosis, spastic diplegia or tetraplegia, and mental retardation (1). The congenital ichthyosis usually brings the patient to medical attention, whereas spasticity and mental retardation become apparent later in the first or second year of life. Preterm birth, pruritus, and ocular abnormalities (including a juvenile macular dystrophy) occur in most cases (2-6).
American Journal of Ophthalmology, Dec 1, 2000
To report the ocular manifestations associated with the Sjögren-Larsson syndrome in a series of p... more To report the ocular manifestations associated with the Sjögren-Larsson syndrome in a series of patients with proven fatty aldehyde dehydrogenase deficiency. To emphasize the clinical importance of the ophthalmological features of the Sjögren-Larsson syndrome. To discuss the metabolic disturbances that might give rise to the ophthalmological picture. Fifteen patients with Sjögren-Larsson syndrome underwent a standardized ophthalmological examination. In patients of appropriate age, and who were able to cooperate, additional investigations were performed. All patients exhibited bilateral, glistening yellow-white crystalline deposits that were located in the innermost retinal layers and appeared during the first 2 years of life. Repeated fundus photography in individual patients showed that the dots became more numerous as the patients got older. Photophobia, subnormal visual acuity, myopia, and astigmatism were found in most of the patients. Fluorescein angiography was performed in three patients and showed a mottled hyperfluorescence of the retinal pigment epithelium, without leakage. Color vision, electroretinography, and electro-oculography could be performed in only a small number of patients and showed no abnormalities. Visual evoked potentials were found to be abnormal in six of eight patients. In Sjögren-Larsson syndrome, patients exhibit highly characteristic bilateral, glistening yellow-white retinal dots from the age of 1 to 2 years onward. The number of dots increases with age. The extent of the macular abnormality does not correlate with the severity of the ichthyosis or with the severity of the neurological abnormalities. A high percentage of patients shows additional ocular signs and symptoms, notably marked photophobia.
Journal of the Neurological Sciences, Sep 1, 2012
In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.
Brain, Jul 1, 2001
Sjögren-Larsson syndrome (SLS) is an autosomal recessively inherited neurocutaneous disorder caus... more Sjögren-Larsson syndrome (SLS) is an autosomal recessively inherited neurocutaneous disorder caused by a deficiency of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH). We report the clinical characteristics and the results of molecular studies in 19 SLS patients. Patients 1-17 show the classical triad of severe clinical abnormalities including ichthyosis, mental retardation and spasticity. Most patients were born preterm, and all patients exhibit ocular abnormalities and pruritus. Electro-encephalography shows a slow background activity, without other abnormalities. MRI of the brain shows an arrest of myelination, periventricular signal abnormalities of white matter and mild ventricular enlargement. Cerebral 1 H-MR spectroscopy reveals a characteristic, abnormal lipid peak. The degree of white matter abnormality in the MRIs and the height of the lipid peak in 1 H-MR spectra do not correlate with the
JIMD reports, Mar 25, 2020
Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused... more Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype-phenotype correlation nor an alternative explanation for the
Neurology, Apr 1, 1999
Objective: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty a... more Objective: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty aldehyde dehydrogenase (FALDH) deficiency. Background: The Sjögren–Larsson syndrome (SLS) was originally defined as a clinical triad consisting of ichthyosis, spastic di- or tetraplegia, and mental retardation, with autosomal recessive inheritance. By now, both the deficiency of the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome. Methods: The clinical findings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to 1H MRS in six patients. Results: The severity of neurologic symptoms showed considerable variation. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidence of retarded myelination and a variable degree of dysmyelination. 1H MRS showed an accumulation of free lipids in the periventricular white matter, even before the stage of visible dysmyelination. Conclusions: The neurologic consequences of FALDH deficiency show considerable variation. The characteristic pattern of ichthyosis and retinal degeneration are seen consistently, yet they are not pathognomonic. MRI and 1H MRS findings suggest an accumulation of long-chain fatty alcohol intermediates, resulting in retarded myelination and dysmyelination.
Item does not contain fulltex
Springer eBooks, 1991
Although it has been known for many years that various disturbances of movement and posture are a... more Although it has been known for many years that various disturbances of movement and posture are associated with lesions in one or another of the basal ganglia (e.g., Wilson 1914; Denny-Brown 1960, 1962; Denny-Brown and Yanagisawa 1976; DeLong and Georgopoulos 1981), it is still not possible to account for individual symptoms, such as tremor, rigidity, or athetosis, in terms of normal or abnormal functioning of a particular component of the basal ganglia. Tremor cannot be produced in animals by lesions limited to structures of the basal ganglia. Neither electrolytic lesions of the SN nor 6-hydroxydopamine (6-OHDA) lesions of the ascending DAergic pathways from the SN and adjacent VTA produced tremor (Poirier 1960; DeLong and Georgopoulos 1981). It is only when lesions of the ascending cerebellar efferents are combined with nigrostriatal lesions that tremor appears. The usual site at which lesions are placed is in the VTA of the midbrain. Here, the lesions interrupt several pathways involving the SN and red nucleus: nigrostriatal, cerebellorubral, cerebellothalamic, and rubroolivary tracts. The conclusion is that parkinsonian rest tremor is not due to a purely striatal DA deficiency, but that damage to other structures, particularly the cerebellorubrothalamic projections, must also be involved. The ventrolateral thalamic nucleus has long been known to be involved in tremor generation (see I.S. Cooper et al. 1968). Hypokinesia and rigidity, cardinal features in Parkinson’s disease, are hypothesized to result from a complex series of changes resulting in an increase in basal ganglia output, particularly to the ventrolateral thalamic nucleus (DeLong and Georgopoulos 1981; Albin et al. 1989).
Journal of Alzheimer's Disease, Nov 19, 2016
People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:
Annals of Neurology, Aug 1, 2009