Axel Petzold

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (187)827.28 Total impact

  • American Journal of Ophthalmology. 10/2014; 158(4):845.
  • American journal of ophthalmology. 10/2014; 158(4):845.
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    ABSTRACT: To investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS).
    Journal of neurology, neurosurgery, and psychiatry. 07/2014;
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    ABSTRACT: Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.
    Nature Reviews Neurology 07/2014; · 15.52 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration.
    Molecular Diagnosis & Therapy 07/2014; · 2.59 Impact Factor
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    ABSTRACT: There is evidence for physiological variation of retinal thicknesses as determined by optical coherence tomography (OCT). We tested if such changes could be explained by hydration and would exceed what may be expected from normal ageing. Subjects (n=26) of a previous study were re-assessed and were randomised to 3 groups of a hydration escalation trial (no hydration, 1× hydration, 2× hydration). Automated retinal layer segmentations were performed for the macular retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). The averaged volumes were calculated for the central foveola, 3mm and 6mm circles of the ETDRS grid. Following oral hydration there were no significant differences of retinal layer thicknesses between the three randomised groups in any of the ETDRS regions at any time-point. Ageing related changes were significant over an 18month period for the GCL. The negative outcome of this trial implies that, until the causes for the observed variation are resolved, investigators may need to accept, and include into trial power calculations, a small degree of variation (<1%) of quantitative SD-OCT imaging either due to human physiology or instrument/software related factors.
    Journal of the neurological sciences. 06/2014;
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    ABSTRACT: To investigate the coexistence of anterograde and retrograde trans-synaptic axonal degeneration, and to explore the relationship between selective visual pathway damage and global brain involvement in longstanding multiple sclerosis (MS).
    Journal of neurology, neurosurgery, and psychiatry. 06/2014;
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    ABSTRACT: Neurofilaments (Nf) are major structural proteins that occur exclusively in neurons. In spinal cord injury (SCI), the severity of disease is quantified by clinical measures that have limited sensitivity and reliability, and no blood-based biomarker has been established to further stratify the degree of injury. We aimed to examine a serum-based NfL immunoassay as predictor of the clinical outcome in SCI.
    Journal of neurology, neurosurgery, and psychiatry. 06/2014;
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    ABSTRACT: Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research.
    Multiple sclerosis (Houndmills, Basingstoke, England). 06/2014;
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    ABSTRACT: Multiple sclerosis (MS) is a primary inflammatory demyelinating disease associated with a probably secondary progressive neuronegenerative component. Impaired mitochondrial functioning has been hypothesised to drive neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of our multicentre study was to determine whether MS patients had values of circulating lactate different from those of controls. Patients (n=613) were recruited, assessed for disability and clinically classified (relapling-remitting, secondary progressive, primary progressive) at the Catholic University of Rome, Italy (n=281), at the MS Centre Amsterdam, The Netherlands (n=158) and at the S. Camillo Forlanini Hospital, Rome, Italy (n=174). Serum lactate levels were quantified spectrophotometrically with the analyst being blinded to all clinical information. In patients with MS serum lactate was three times higher (3.04±1.26mmol/l) than that of healthy controls (1.09±0.25mmol/l, p<0.0001) and increased across clinical groups, with higher levels in cases with a progressive than with a relapsing-remitting disease course. In addition, there was a linear correlation between serum lactate levels and the EDSS (R2=0.419; p<0.001). These data support the hypothesis that mitochondrial dysfunction is an important feature in MS and of particular relevance to the neurodegenerative phase of the disease. Measurement of serum lactate in MS might be a relative inexpensive test for longitudinal monitoring of "virtual hypoxia" in MS. and also a secondary outcome for treatment trials aimed to improve mitochondrial function in patients with MS.
    Biochimica et Biophysica Acta 04/2014; · 4.66 Impact Factor
  • Lisanne J Balk, Axel Petzold
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    ABSTRACT: SUMMARY Multiple sclerosis (MS) is a disorder characterized by inflammation and neuroaxonal degeneration. The latter is held responsible for the irreversible disability in patients with MS. The eye is a unique window into the brain. With the advent of optical coherence tomography, accurate quantification of retinal layer thickness has become feasible. Neuroaxonal degeneration affecting the retinal layers is structurally and functionally related to pathology in the visual pathways, which is most severe following MS optic neuritis. This is relevant to recognize because MS optic neuritis may mask the subtle thinning of retinal layers associated with global CNS atrophy, which is also related to more global loss of neurological function. Taken together, optical coherence tomography stands at the brink of becoming a validated imaging biomarker for monitoring neurodegeneration in MS and to provide end points for clinical trials.
    Neurodegenerative disease management. 04/2014; 4(2):165-76.
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    ABSTRACT: Trans-synaptic axonal degeneration is a mechanism by which neurodegeneration can spread from a sick to a healthy neuron in the central nervous system. This study investigated to what extent trans-synaptic axonal degeneration takes place within the visual pathway in multiple sclerosis (MS). A single-centre study, including patients with long-standing MS and healthy controls. Structural imaging of the brain (MRI) and retina (spectral-domain optical coherence tomography) were used to quantify the extent of atrophy of individual retinal layers and the primary and secondary visual cortex. Generalised estimation equations and multivariable regression analyses were used for comparisons. Following rigorous quality control (OSCAR-IB), data from 549 eyes of 293 subjects (230 MS, 63 healthy controls) were included. Compared with control data, there was a significant amount of atrophy of the inner retinal layers in MS following optic neuritis (ON) and also in absence of ON. For both scenarios, atrophy stopped at the level of the inner nuclear layer. In contrast, there was significant localised atrophy of the primary visual cortex and secondary visual cortex in MS following ON, but not in MS in absence of ON. These data suggest that retrograde (trans-synaptic) axonal degeneration stops at the inner nuclear layer, a neuronal network capable of plasticity. In contrast, there seems to be no neuroplasticity of the primary visual cortex, rendering the structure vulnerable to anterograde (trans-synaptic) degeneration.
    Journal of neurology, neurosurgery, and psychiatry 01/2014; · 4.87 Impact Factor
  • Axel Petzold, Gordon T Plant
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    ABSTRACT: The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica spectrum disorder (NMO), multiple sclerosis associated optic neuritis (MSON) and unclassified forms (UCON). Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies.
    Autoimmunity reviews 01/2014; · 6.37 Impact Factor
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    ABSTRACT: The heterogeneity of the disease course in multiple sclerosis (MS) remains a challenge for patient management and clinical trials. The objective of this paper is to investigate the relationship between disease course heterogeneity and retinal layer thicknesses in MS. A total of 230 MS patients and 63 healthy control subjects were included. Spectral-domain OCT scanning of the peripapillary and macular regions was performed, followed by automated eight-layer segmentation. Generalised estimation equations were used for comparisons. Receiver operating characteristic (ROC) curves were calculated for distinguishing a benign from a typical disease course. Primary progressive patients showed relative preservation of inner retinal layers, compared to the relapsing onset MS types. Only in MS eyes without optic neuritis did patients with typical MS show more severe thinning of the inner retinal layers (RNFL to INL) compared to patients with a benign disease course, even after an average disease course of 20 years. The thicknesses, particularly of the innermost retinal layers (RNFL, GCC), were significantly related to the heterogeneous disease course in MS. The relative preservation of these layers in primary progressive and benign MS suggests rather limited susceptibility of the retina to neurodegeneration, which may be relevant for future neurodegenerative treatment trials employing OCT as a secondary outcome measure in primary progressive MS.
    Multiple Sclerosis 01/2014; · 4.47 Impact Factor
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    ABSTRACT: Purpose:Microcystic macular oedema (MMO) defines microcysts in the inner nuclear layer (INL) of the retina. MMO was described in multiple sclerosis (MS), but can be found in numerous disorders. Presence of MMO has important prognostic and therapeutic implications, however, the differential diagnosis is unknown. This study aimed to describe the clinical spectrum of MMO. Methods:a single-centre, retrospective cohort study. A bootstrap analysis was performed to reduce the 5,865 patients (22,376 scans), who had undergone OCT imaging between January 2010 and February 2013, to a representative dataset. Presence of MMO was rated by independent observers. Results:The dataset consisted of 1,368 patients (mean age 62, range 4-101 years), 2,589 eyes and 6,449 scans. MMO was present in 133/1,303 (10%) of patients and 0/65 (0%) of healthy controls. The inter-rater agreement for detecting MMO was substantial (0.6) and could be further improved after refining the criteria (0.8). The clinical spectrum included age-related macular degeneration, epiretinal membranes, post-operative lesions, diabetic retinopathy, vascular occlusion, MS (with/without optic neuritis), optic neuropathy, central serous chorioretinopathy, medication and miscellaneous causes. The longitudinal pattern of MMO was transient in 84% of cases. MMO could be associated with an increase or decrease in INL thickness and was predominantly located nasally (48%) and/or temporally (50%). Conclusions: Conclusions: This study substantially widened the clinical spectrum of MMO. Diagnostic criteria were refined and validated. The associated phenotype may imply Müller cell dysfunction within the watershed zone. The longitudinal data and evidence from previous studies suggest follow-up of these patients and their visual function.
    Investigative ophthalmology & visual science 01/2014; · 3.43 Impact Factor
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    ABSTRACT: A frequently observed local measurement artifact with spectral domain OCT is caused by the void signal of the retinal vasculature. This study investigated the effect of suppression of blood vessel artifacts with and without retinal hyperaemia. Spectral domain OCT scans, centred on the optic nerve head, were performed in 46 healthy subjects (92 eyes). Baseline scans were made during rest, while for the follow-up scan, 23 subjects (50 %) performed strenuous physical exercise. Systemic and retinal hyperaemia were quantified. Quantification of retinal nerve fibre layer (RNFL) thickness was performed with and without suppression of retinal blood vessel artifacts. The potential systematic effect on RNFL thickness measurements was analysed using Bland-Altman plots. At baseline (no retinal hyperaemia), there was a systematic difference in RNFL thickness (3.4 μm, limits of agreement -0.9 to 7.7) with higher values if blood vessel artifacts were not suppressed. There was significant retinal hyperaemia in the exercise group (p < 0.0001). Baseline thickness increased from 93.18 to 93.83 μm (p < 0.05) in the exercise group using the algorithm with blood vessel artifact suppression, but no significant changes were observed using the algorithm without blood vessel artifact suppression. Retinal hyperaemia leads to blood vessel artifacts which are relevant to the precision of OCT layer segmentation algorithms. The two algorithms investigated in this study can not be used interchangeably. The algorithm with blood vessel artifact suppression was more sensitive in detecting small changes in RNFL thickness. This may be relevant for the use of OCT in a range of neurodegenerative diseases were only a small degree of retinal layer atrophy have been found so far.
    Journal of Neurology 01/2014; · 3.58 Impact Factor
  • Investigative ophthalmology & visual science. 01/2014; 55(8):4728.
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    ABSTRACT: Multiple sclerosis (MS) is a primary inflammatory demyelinating disease associated with a probably secondary progressive neurodegenerative component. Impaired mitochondrial functioning has been hypothesized to drive neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of our multicentre study was to determine whether MS patients had values of circulating lactate different from those of controls. Patients (n = 613) were recruited, assessed for disability and clinically classified (relapsing–remitting, secondary progressive, primary progressive) at the Catholic University of Rome, Italy (n = 281), at the MS Centre Amsterdam, The Netherlands (n = 158) and at the S. Camillo Forlanini Hospital, Rome, Italy (n = 174). Serum lactate levels were quantified spectrophotometrically with the analyst being blinded to all clinical information. In patients with MS serum lactate was three times higher (3.04 ± 1.26 mmol/l) than that of healthy controls (1.09 ± 0.25 mmol/l, p < 0.0001) and increased across clinical groups, with higher levels in cases with a progressive than with a relapsing–remitting disease course. In addition, there was a linear correlation between serum lactate levels and the expanded disability scale (EDSS) (R2 = 0.419; p < 0.001). These data support the hypothesis that mitochondrial dysfunction is an important feature in MS and of particular relevance to the neurodegenerative phase of the disease. Measurement of serum lactate in MS might be a relative inexpensive test for longitudinal monitoring of “virtual hypoxia” in MS and also a secondary outcome for treatment trials aimed to improve mitochondrial function in patients with MS.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 01/2014; · 4.91 Impact Factor
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    ABSTRACT: IMPORTANCE Recent reports on chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) suggest that patients who have a relapse respond very well and that disease progression can be avoided if timely corticosteroid therapy is started. We report on a well-documented patient who presented with clinical, radiological, and pathological characteristics of CLIPPERS and who had an unfavorable outcome. OBSERVATIONS We present the clinical, imaging, laboratory, brain biopsy, and autopsy findings of a 57-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. During follow-up, however, treatment failed, and he had a biopsy-confirmed diagnosis of lymphomatoid granulomatosis that evolved into fatal B-cell lymphoma of the central nervous system. CONCLUSIONS AND RELEVANCE The clinical and imaging features of CLIPPERS include an abundance of differential diagnoses, and the follow-up periods of the described cases classified as CLIPPERS have been limited. Therefore, the question remains whether CLIPPERS is an actual new disease entity or represents a syndrome that includes different overlapping diseases and their prestages. Our case report shows that a typical presentation of CLIPPERS does not uniformly imply a favorable outcome, even when timely treatment regimens have been given.
    JAMA neurology. 11/2013; 70(11):1459-60.
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    ABSTRACT: The application of spectral domain optical coherence tomography as a surrogate for neurodegeneration in a range of neurological disorders demands better understanding of the physiological variation of retinal layer thicknesses, which may mask any value of this emerging outcome measure. A prospective study compared retinal layer thicknesses between control subjects (n = 15) and runners (n = 27) participating in a 10-km charity run. Three scans were performed using an eye-tracking function (EBF) and automated scan registration for optimal precision at (1) baseline, (2) directly after the run, and (3) following a rehydration period. Retinal layer segmentation was performed with suppression of axial retinal vessel signal artifacts. Following the run, there was an increase in the relative retinal nerve fibre layer (p = 0.018), the combined inner plexiform/ganglion cell layer (p = 0.038), and the outer nuclear layer (p = 0.018) in runners compared to controls. The initial increase of thickness in the outer nuclear layer of runners (p < 0.0001) was likely related to (noncompliant) rehydration during exercise. Following a period of rest and rehydration, the difference in thickness change for all retinal layers, except the retinal nerve fibre layer (RNFL) (p < 0.05), disappeared between the two groups. There is a quantifiable change in the axial thickness of retinal layersthat which can be explained by an increase in the cellular volume. This effect may potentially be caused by H2O volume shifts.
    Journal of Neurology 10/2013; · 3.58 Impact Factor

Publication Stats

3k Citations
827.28 Total Impact Points

Institutions

  • 2010–2014
    • VU University Medical Center
      • • Department of Neurology
      • • Department of Molecular Cell Biology and Immunology
      Amsterdamo, North Holland, Netherlands
    • Universitätsspital Basel
      • Neurobiology Unit
      Basel, BS, Switzerland
    • University of Catania
      • Department of Chemical Sciences
      Catania, Sicily, Italy
  • 2009–2014
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 2013
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2001–2013
    • Moorfields Eye Hospital NHS Foundation Trust
      • Department of Medical Retina
      Londinium, England, United Kingdom
  • 2012
    • Klinički centar Srbije
      Beograd, Central Serbia, Serbia
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands
    • Methodist Rehabilitation Center
      Jackson, Mississippi, United States
    • Lund University
      • Department of Clinical Sciences
      Lund, Skane, Sweden
  • 2011
    • Technische Universität München
      München, Bavaria, Germany
    • VU University Amsterdam
      • Department of Clinical Chemistry
      Amsterdam, North Holland, Netherlands
    • Kwangwoon University
      • Department of Chemistry
      Seoul, Seoul, South Korea
  • 2009–2011
    • The National Institute of Neurology and Neurosurgery
      Tlalpam, The Federal District, Mexico
  • 2006–2011
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
    • Institute for Optimum Nutrition
      TW9, England, United Kingdom
  • 2002–2011
    • University College London
      • • Department of Neuroinflammation
      • • Institute of Neurology
      Londinium, England, United Kingdom
  • 2008–2010
    • Medical University of Lublin
      • Department of Neurology
      Lublin, Lublin Voivodeship, Poland
    • University of Southampton
      • Clinical Neurosciences
      Southampton, ENG, United Kingdom
  • 2006–2010
    • Universität Ulm
      • Clinic of Neurology
      Ulm, Baden-Wuerttemberg, Germany