The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Irina Alafuzoff - One of the best experts on this subject based on the ideXlab platform.

  • Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus
    2016
    Co-Authors: Okko T. Pyykkö, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen, Hilkka Soininen
    Abstract:

    Background: The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) is unknown. Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91 % shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPPa were lower (p,0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brai

  • cerebrospinal fluid biomarker and Brain Biopsy findings in idiopathic normal pressure hydrocephalus
    PLOS ONE, 2014
    Co-Authors: Okko T Pyykko, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Toni T Seppala, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen
    Abstract:

    Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the Brain Biopsy. Quantified Ab load in the Brain Biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the Brain Biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.

  • csf biomarkers for alzheimer disease correlate with cortical Brain Biopsy findings
    Neurology, 2012
    Co-Authors: Toni T Seppala, Okko T Pyykko, Jaana Rummukainen, Ossi Nerg, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Henrik Zetterberg, Seppo Helisalmi, Mikko Hiltunen
    Abstract:

    Objective: To assess the relationship between Alzheimer disease (AD)–related pathologic changes in frontal cortical Brain Biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical Biopsy with the final clinical diagnosis of AD. Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical Brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results: The patients with Aβ plaques in the cortical Biopsy had lower ( p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical Biopsy had lower ( p = 0.014) Aβ42 but higher ( p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical Biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE e4 carrier status and age but not by CSF Aβ42 or tau levels. Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical Brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.

  • cortical Brain Biopsy in long term prognostication of 468 patients with possible normal pressure hydrocephalus
    Neurodegenerative Diseases, 2012
    Co-Authors: Ville Leinonen, Okko T Pyykko, Jaana Rummukainen, Anne M Koivisto, Irina Alafuzoff, Mikael Von Und Zu Fraunberg, Juha E Jaaskelainen, Hilkka Soininen, Jaakko Rinne, Sakari Savolainen
    Abstract:

    Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical Brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those Brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of Brain Biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical Brain Biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical Biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain Biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.

  • post mortem findings in 10 patients with presumed normal pressure hydrocephalus and review of the literature
    Neuropathology and Applied Neurobiology, 2012
    Co-Authors: Ville Leinonen, Jaana Rummukainen, Anne M Koivisto, Irina Alafuzoff, Sakari Savolainen, Juha E Jaaskelainen, Hilkka Soininen, Anna Sutela, Ritva Vanninen
    Abstract:

    V. Leinonen, A. M. Koivisto, S. Savolainen, J. Rummukainen, A. Sutela, R. Vanninen, J. E. Jaaskelainen, H. Soininen and I. Alafuzoff (2012) Neuropathology and Applied Neurobiology38, 72–86 Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature Aims: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain Biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of Biopsy findings is scarce. Here we review and report Brain Biopsy and post-mortem neuropathological findings in patients with presumed NPH. Methods: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical Biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. Results: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-β (Aβ) aggregates in their frontal cortical Biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. Conclusions: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain Biopsy can be used to detect Aβ aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.

Sakari Savolainen - One of the best experts on this subject based on the ideXlab platform.

  • Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus
    2016
    Co-Authors: Okko T. Pyykkö, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen, Hilkka Soininen
    Abstract:

    Background: The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) is unknown. Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91 % shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPPa were lower (p,0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brai

  • cerebrospinal fluid biomarker and Brain Biopsy findings in idiopathic normal pressure hydrocephalus
    PLOS ONE, 2014
    Co-Authors: Okko T Pyykko, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Toni T Seppala, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen
    Abstract:

    Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the Brain Biopsy. Quantified Ab load in the Brain Biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the Brain Biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.

  • cortical Brain Biopsy in long term prognostication of 468 patients with possible normal pressure hydrocephalus
    Neurodegenerative Diseases, 2012
    Co-Authors: Ville Leinonen, Okko T Pyykko, Jaana Rummukainen, Anne M Koivisto, Irina Alafuzoff, Mikael Von Und Zu Fraunberg, Juha E Jaaskelainen, Hilkka Soininen, Jaakko Rinne, Sakari Savolainen
    Abstract:

    Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical Brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those Brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of Brain Biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical Brain Biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical Biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain Biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.

  • post mortem findings in 10 patients with presumed normal pressure hydrocephalus and review of the literature
    Neuropathology and Applied Neurobiology, 2012
    Co-Authors: Ville Leinonen, Jaana Rummukainen, Anne M Koivisto, Irina Alafuzoff, Sakari Savolainen, Juha E Jaaskelainen, Hilkka Soininen, Anna Sutela, Ritva Vanninen
    Abstract:

    V. Leinonen, A. M. Koivisto, S. Savolainen, J. Rummukainen, A. Sutela, R. Vanninen, J. E. Jaaskelainen, H. Soininen and I. Alafuzoff (2012) Neuropathology and Applied Neurobiology38, 72–86 Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature Aims: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain Biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of Biopsy findings is scarce. Here we review and report Brain Biopsy and post-mortem neuropathological findings in patients with presumed NPH. Methods: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical Biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. Results: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-β (Aβ) aggregates in their frontal cortical Biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. Conclusions: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain Biopsy can be used to detect Aβ aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.

  • amyloid and tau proteins in cortical Brain Biopsy and alzheimer s disease
    Annals of Neurology, 2010
    Co-Authors: Ville Leinonen, Okko T Pyykko, Jaana Rummukainen, Anne M Koivisto, Sakari Savolainen, Juuso Tamminen, Tomi Tillgren, Sannakaisa Vainikka, Juhani Molsa
    Abstract:

    Objective: Amyloid-beta(A beta) aggregates are presumed to be found in the Brain at an early stage of Alzheimer's disease (AD) but have seldom been assessed by Brain Biopsy during life in often elderly patients. Methods: Between 1991 and 2006 we evaluated 468 patients with suspected normal pressure hydrocephalus with intraventricular pressure monitoring and a right frontal cortical Biopsy sample immunostained for A beta and hyperphosphorylated tau (HP tau). Adequate samples and the clinical follow-up data until death or the end of 2008, available in 433 cases, were reviewed for the clinical signs of dementia, including AD. Logistic regression analysis was used to analyze whether A beta and/or HP tau in the Biopsy samples obtained during life predicted development of cognitive impairment, in particular, AD. Results: Of the 433 frontal cortical samples, 42 (10%) displayed both A beta and HP tau, 144 (33%) A beta only, and 247 (57%) neither A beta nor HP tau. In a median follow-up time of 4.4 years, 94 patients (22%) developed clinical AD. The presence of both A beta and HP tau was strongly associated (odds ratio [OR], 68.2; 95% confidence interval [Cl], 22.1-210) and A beta alone significantly associated (OR, 10.8; 95% Cl, 4.9-23.8) with the clinical diagnosis of AD. Interpretation: This is the largest follow-up study of patients assessed for the presence of A beta and HP tau in frontal cortical Brain Biopsy samples. 1) The presence of A beta and HP tau spoke strongly for the presence or later development of clinical AD; 2) A beta alone was suggestive of AD; and 3) the absence of A beta and HP tau spoke against a later clinical diagnosis of AD.

Peter Mcl Black - One of the best experts on this subject based on the ideXlab platform.

  • comparative effectiveness of frame based frameless and intraoperative magnetic resonance imaging guided Brain Biopsy techniques
    World Neurosurgery, 2015
    Co-Authors: Yi Lu, Cecil Yeung, Alireza Radmanesh, Robert Wiemann, Peter Mcl Black, Alexandra J Golby
    Abstract:

    Objective To compare the diagnostic yield and safety profiles of intraoperative magnetic resonance imaging (MRI)–guided needle Brain Biopsy with 2 traditional Brain Biopsy methods: frame-based and frameless stereotactic Brain Biopsy. Methods A retrospective analysis was performed of 288 consecutive needle Brain biopsies in 277 patients undergoing stereotactic Brain Biopsy with any of the 3 Biopsy methods at Brigham and Women’s Hospital from 2000–2008. Variables including age, sex, history of radiation and previous surgery, pathology results, complications, and postoperative length of hospital stay were analyzed. Results Over the course of 8 years, 288 Brain biopsies were performed. Of these, 253 (87.8%) biopsies yielded positive diagnostic tissue. Young age ( Conclusions Frame-based, frameless stereotactic, and intraoperative MRI–guided Brain needle Biopsy techniques have comparable diagnostic yield for patients with no prior treatments (either radiation or surgery). Intraoperative MRI–guided Brain Biopsy is associated with fewer serious adverse events and shorter hospital stay.

  • frameless stereotactic neurosurgery using intraoperative magnetic resonance imaging stereotactic Brain Biopsy
    Neurosurgery, 2000
    Co-Authors: Thomas M Moriarty, Alfredo Quinoneshinojosa, Paul S Larson, Eben Alexander, Langham P Gleason, Richard B Schwartz, Ferenc A Jolesz, Peter Mcl Black
    Abstract:

    OBJECTIVE: To assess the application accuracy of intraoperative magnetic resonance imaging for frameless stereotactic surgery, and to evaluate the performance of intraoperative magnetic resonance imaging for the Brain Biopsy, a standard stereotactic procedure. METHODS: A series of spatial coordinate and phantom experiments were performed to analyze the application accuracy of the system. A prospective analysis of 68 consecutive patients undergoing stereotactic Brain Biopsy was then performed. RESULTS: The spatial coordinate experiments revealed a mean overall error in acquisition of 0.2 mm. The phantom experiments demonstrated a 1:1 correlation between the magnetic resonance image of a stereotactically guided probe and its relationship to a target and the actual relationship of the probe and target. Sixty-eight Brain biopsies were successfully performed in all intracranial compartments except the sella. The radiographic abnormality was localized successfully in all patients (100%). Sixty-six (97.1%) of the biopsies yielded diagnostic tissue. Two biopsies (2.9%) were complicated by intraparenchymal hemorrhage. One expanding temporal lobe hemorrhage was evacuated by immediate craniotomy in the magnet with no postoperative sequelae. A deep hemorrhage from a lymphoma was managed conservatively with interval resolution of symptoms. There were no infections. There was no perioperative mortality. CONCLUSION: Intraoperative magnetic resonance imaging allows excellent target localization, provides true real-time imaging to account for anatomic changes during surgery, and permits intraoperative confirmation that the Biopsy needle has reached the targeted lesion. Immediate postoperative imaging in the operating room allows assessment of adverse events and the potential for immediate management of hemorrhagic complications. (Neurosurgery 47:1138‐1146, 2000)

Anne M Koivisto - One of the best experts on this subject based on the ideXlab platform.

  • s 18f thk 5117 pet and 11c pib pet imaging in idiopathic normal pressure hydrocephalus in relation to confirmed amyloid β plaques and tau in Brain biopsies
    Journal of Alzheimer's Disease, 2018
    Co-Authors: Anne M Koivisto, Ville Leinonen, Tuomas Rauramaa, Jarkko Johansson, Astrid Bottelbergs, Ina Tesseur, Peter Van Der Ark, Darrel Pemberton, Juha E Jaaskelainen
    Abstract:

    Background Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in Brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with Brain Biopsy verified tau pathology in vivo. Objective Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in Brain Biopsy. Methods Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical Brain Biopsy and CSF Aβ1 - 42, total tau, and P-tau181 measures, underwent Brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging. Results Seven patients had amyloid-β (Aβ, 4G8) plaques, two both Aβ and phosphorylated tau (Pτ, AT8) and one only Pτ in Biopsy. As expected, increased Brain Biopsy Aβ was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either Brain Biopsy Pτ or CSF P-tau181 or total tau. Conclusions S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in Brain Biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aβ and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.

  • Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus
    2016
    Co-Authors: Okko T. Pyykkö, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen, Hilkka Soininen
    Abstract:

    Background: The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) is unknown. Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91 % shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPPa were lower (p,0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the brai

  • cerebrospinal fluid biomarker and Brain Biopsy findings in idiopathic normal pressure hydrocephalus
    PLOS ONE, 2014
    Co-Authors: Okko T Pyykko, Miikka Lumela, Jaana Rummukainen, Ossi Nerg, Toni T Seppala, Sannakaisa Herukka, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Sakari Savolainen
    Abstract:

    Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to Brain Biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical Brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06). CSF sAPP isoform levels showed no association to Ab or HPt in the Brain Biopsy. Quantified Ab load in the Brain Biopsy showed a negative correlation with CSF levels of Ab42 in ventricular (r = 20.295, p = 0.003) and lumbar (r = 20.356, p = 0.01) samples, while the levels of Ab38 and Ab40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the Brain Biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions: The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD.

  • csf biomarkers for alzheimer disease correlate with cortical Brain Biopsy findings
    Neurology, 2012
    Co-Authors: Toni T Seppala, Okko T Pyykko, Jaana Rummukainen, Ossi Nerg, Anne M Koivisto, Irina Alafuzoff, Lakshman Puli, Henrik Zetterberg, Seppo Helisalmi, Mikko Hiltunen
    Abstract:

    Objective: To assess the relationship between Alzheimer disease (AD)–related pathologic changes in frontal cortical Brain Biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical Biopsy with the final clinical diagnosis of AD. Methods: In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical Brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results: The patients with Aβ plaques in the cortical Biopsy had lower ( p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical Biopsy had lower ( p = 0.014) Aβ42 but higher ( p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical Biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE e4 carrier status and age but not by CSF Aβ42 or tau levels. Conclusions: Amyloid plaques and hyperphosphorylated tau in cortical Brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.

  • cortical Brain Biopsy in long term prognostication of 468 patients with possible normal pressure hydrocephalus
    Neurodegenerative Diseases, 2012
    Co-Authors: Ville Leinonen, Okko T Pyykko, Jaana Rummukainen, Anne M Koivisto, Irina Alafuzoff, Mikael Von Und Zu Fraunberg, Juha E Jaaskelainen, Hilkka Soininen, Jaakko Rinne, Sakari Savolainen
    Abstract:

    Normal pressure hydrocephalus (NPH) can be alleviated by cerebrospinal fluid shunting but the differential diagnosis and patient selection are challenging. Intraventricular intracranial pressure monitoring as part of the diagnostic workup as well as shunting enable to obtain cortical Brain biopsies to detect amyloid-β (Aβ) and hyperphosphorylated tau (HPτ), the hallmark lesions of Alzheimer's disease (AD). In possible NPH, Aβ alone indicates an increased risk of AD and when present with HPτ probable AD, but the effect of those Brain lesions on survival is not known. The aim of this study was to evaluate the predictive value of Brain Biopsy for the long-term outcome of possible NPH. Between 1991 and 2006, the Neurosurgery Department of the Kuopio University Hospital evaluated 468 patients for possible NPH by intraventricular intracranial pressure monitoring and frontal cortical Brain Biopsy immunostained against Aβ and HPτ. All patients were followed up until the end of 2008 (n = 201) or death (n = 267) with a median follow-up of 4.6 years (range 0-17). Logistic regression analysis with Cox models was applied. Out of the 468 cases, Aβ was detected in 197 (42%) cortical biopsies, and together with HPτ in 44 (9%). Aβ alone indicated increased risk of AD and with HPτ probable AD, but it did not affect survival. Vascular aetiology was the most frequent cause of death. Cortical Biopsy findings indicate that NPH is at present a heterogeneous syndrome and has notable overlapping with AD. Brain Biopsy did not predict survival but may open a novel research window to study the pathobiology of neurodegeneration.

Flegel Thomas - One of the best experts on this subject based on the ideXlab platform.

  • Accuracy of a magnetic resonance imaging-based 3D printed stereotactic Brain Biopsy device in dogs
    2020
    Co-Authors: Gutmann Sarah, Winkler Dirk, Müller Marcel, Möbius Robert, Fischer Jean-pierre, Böttcher P., Kiefer Ingmar, Grunert Ronny, Flegel Thomas
    Abstract:

    BACKGROUND: Brain Biopsy of intracranial lesions is often necessary to determine specific therapy. The cost of the currently used stereotactic rigid frame and optical tracking systems for Brain Biopsy in dogs is often prohibitive or accuracy is not sufficient for all types of lesion. OBJECTIVES: To evaluate the application accuracy of an inexpensive magnetic resonance imaging-based personalized, 3D printed Brain Biopsy device. ANIMALS: Twenty-two dog heads from cadavers were separated into 2 groups according to body weight (20 kg).METHODS: Experimental study. Two target points in each cadaver head were used (target point 1: caudate nucleus, target point 2: piriform lobe). Comparison between groups was performed using the independent Student's t test or the nonparametric Mann-Whitney U Test. RESULTS: The total median target point deviation was 0.83 mm (range 0.09-2.76 mm). The separate median target point deviations for target points 1 and 2 in all dogs were 0.57 mm (range: 0.09-1.25 mm) and 0.85 mm (range: 0.14-2.76 mm), respectively. CONCLUSION AND CLINICAL IMPORTANCE: This magnetic resonance imaging-based 3D printed stereotactic Brain Biopsy device achieved an application accuracy that was better than the accuracy of most Brain Biopsy systems that are currently used in veterinary medicine. The device can be applied to every size and shape of skull and allows precise positioning of Brain Biopsy needles in dogs

  • Accuracy of a magnetic resonance imaging‐based 3D printed stereotactic Brain Biopsy device in dogs
    2020
    Co-Authors: Gutmann Sarah, Winkler Dirk, Müller Marcel, Möbius Robert, Fischer Jean-pierre, Kiefer Ingmar, Grunert Ronny, Böttcher Peter, Flegel Thomas
    Abstract:

    Background: Brain Biopsy of intracranial lesions is often necessary to determine specific therapy. The cost of the currently used stereotactic rigid frame and optical tracking systems for Brain Biopsy in dogs is often prohibitive or accuracy is not sufficient for all types of lesion. Objectives: To evaluate the application accuracy of an inexpensive magnetic resonance imaging‐based personalized, 3D printed Brain Biopsy device. Animals: Twenty‐two dog heads from cadavers were separated into 2 groups according to body weight (20 kg). Methods: Experimental study. Two target points in each cadaver head were used (target point 1: caudate nucleus, target point 2: piriform lobe). Comparison between groups was performed using the independent Student's t test or the nonparametric Mann‐Whitney U Test. Results: The total median target point deviation was 0.83 mm (range 0.09‐2.76 mm). The separate median target point deviations for target points 1 and 2 in all dogs were 0.57 mm (range: 0.09‐1.25 mm) and 0.85 mm (range: 0.14‐2.76 mm), respectively. Conclusion and Clinical Importance: This magnetic resonance imaging‐based 3D printed stereotactic Brain Biopsy device achieved an application accuracy that was better than the accuracy of most Brain Biopsy systems that are currently used in veterinary medicine. The device can be applied to every size and shape of skull and allows precise positioning of Brain Biopsy needles in dogs

  • Accuracy of a new MRI-based patient-individual stereotactic Brain Biopsy device in the dog: Presentation held at Forum American College of Veterinary Internal Medicine 2018, June 13-16, 2018, Seattle, Washington
    2018
    Co-Authors: Flegel Thomas, Winkler Dirk, Müller Marcel, Möbius Robert, Kiefer Ingmar, Grunert Ronny, Böttcher Peter, Fischer J.-p., Gutmann Sarah
    Abstract:

    The aim of the study was to determine the precision of the novel MRI-based patient-individual stereotactic Brain Biopsy device in dogs. Twenty-two canine cadavers with 2 target points each were used to determine accuracy. First, specific bone anchors and MRI-markers were secured to canine cadaver heads. Afterwards CT and MRI examinations of the heads were performed. Two target points and corresponding trajectories were defined on each MRI: left caudate nucleus and right piriform lobe. Based on MR-images, patient-individual frames including rigid needle placement ports to reach defined target points were constructed and printed with a 3D-printer. The needle was to enter the Brain in a gyrus and not to penetrate the ventricles. The frames were secured to the bone anchors. Minimal-invasive access to the Brain was created using a tool guide. The Biopsy needle was placed through the needle placement port up to the predetermined depth. Afterwards CT examinations of the heads with Biopsy needles placed in each target point were performed. Needle placement error was determined after fusion of MRI and CT examinations. Error was defined as deviation in mm between needle tip and anticipated target points. The total median needle placement error for all 42 target points was 0.84 mm (range: 0.09–2.76; outlier: 4.11). The median needle placement error for the caudate nucleus only was 0.67 mm (range: 0.09–1.25) and for the piriform lobe 0.85 mm (range: 0.14–2.76). Therefore, the MRI-based patient-individual stereotactic Brain Biopsy device reaches higher accuracy than most other described Brain Biopsy systems

  • Accuracy study of a 3D printed patient specific Brain Biopsy system for veterinary medicine: Network session 3: Therapy of diseases of the musculoskeletal system Biomedical Engineering
    2017
    Co-Authors: Müller Marcel, Winkler Dirk, Möbius Robert, Flegel Thomas, Hanemann Sarah, Scholz Sebastian, Grunert Ronny
    Abstract:

    The sampling of Brain tissue in veterinary medicine usually underlies a freehand performance without exact localization. The aim of the project was the accuracy evaluation of a 3D-printed subject specific system for Brain Biopsy in dogs. At the beginning of the procedure, three small bone screws were fixed (bilateral and occipital/frontal) to the dog skull. Subsequently, three MR-markers filled with contrast agent were adapted and MRI scans performed (layer-thickness 1.0 mm). Within the MR images the coordinates of the target and entry point are determined by the surgeon. For evaluation an additional pre-CT (layer-thickness 0.7 mm) was realized. After image recording the MR-markers were removed. Due to a self-made algorithm a patient individual template was constructed. The final Biopsy device made of ABS M30 was produced by a 3D printer (FDM).To perform the Biopsy the device was connected with the already embedded bone screws. Through a guidance track the skull was minimally invasive accessed at the intended location. Controlled by a depth stop the Biopsy needle could be exactly moved in a desired direction up to the target point. A further post-CT (thickness 0.7 mm) with inserted needle was performed to determine the final position of the Biopsy needle tip. For receiving information about the difference between preoperative planned and achieved tip position the pre-CT was matched with the post-CT. Therefor 10 dog cadavers (n=20 target points) were applied. The results showed an accuracy of 0.58 mm ± 0.34 mm (ranging from 0.09 mm to 1.17 mm) between the preoperative planned and the achieved needle position. A patient specific 3D-printed Biopsy system based on MR images was developed which enables a high precise Brain Biopsy. Moreover, the system matches up to current costly diagnosis techniques of image-guided neurosurgery and robot systems. Prospectively, it shall be transferred to human medicine