Neuropathological findings in possible normal pressure hydrocephalus : A post-mortem study of 29 cases with lifelines

Publisher Copyright: © 2022, University of Muenster. All rights reserved.Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Premortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer’s disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of “hydrocephalic dementia” as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.Peer reviewe

Cerebrospinal Fluid Diagnostics of Alzheimer’s Disease in Patients with Idiopathic Normal Pressure Hydrocephalus

Background: Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers.// Objective: Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value.// Methods: Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals (n = 33) and patients with diagnosed AD and no iNPH (n = 39).// *-31pt// Results: Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*Aβ₁ ₋ ₄₂, 0.779*t-Tau, and 0.610*P-Tau₁₈₁) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau₁₈₁ to Aβ₁ ₋ ₄₂ was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824). Conclusion: Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau₁₈₁ /Aβ₁ ₋ ₄₂ ratio showed some utility in the diagnosis of AD in iNPH patients

Concordance of Alzheimer's Disease-Related Biomarkers Between Intraventricular and Lumbar Cerebrospinal Fluid in Idiopathic Normal Pressure Hydrocephalus

BACKGROUND: Alzheimer's disease cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau 181 (P-tau181) are widely used. However, concentration gradient of these biomarkers between intraventricular (V-CSF) and lumbar CSF (L-CSF) has been demonstrated in idiopathic normal pressure hydrocephalus (iNPH), potentially affecting clinical utility. OBJECTIVE: Here we aim to provide conversion factors for clinical and research use between V-CSF and L-CSF. METHODS: Altogether 138 iNPH patients participated. L-CSF samples were obtained prior to shunt surgery. Intraoperative V-CSF samples were obtained from 97 patients. Post-operative follow-up L- and V-CSF (shunt reservoir) samples of 41 patients were obtained 1-73 months after surgery and then after 3, 6, and 18 months. CSF concentrations of Aβ42, T-tau, and P-tau181 were analyzed using commercial ELISA assays. RESULTS: Preoperative L-CSF Aβ42, T-tau, and P-tau181 correlated to intraoperative V-CSF (ρ= 0.34-0.55, p < 0.001). Strong correlations were seen between postoperative L- and V-CSF for all biomarkers in every follow-up sampling point (ρs Aβ 42: 0.77-0.88, T-tau: 0.91-0.94, P-tau181: 0.94-0.96, p < 0.0001). Regression equations were determined for intraoperative V- and preoperative L-CSF (Aβ 42: V-CSF = 185+0.34*L-CSF, T-tau: Ln(V-CSF) = 3.11+0.49*Ln(L-CSF), P-tau181: V-CSF = 8.2+0.51*L-CSF), and for postoperative V- and L-CSF (Aβ 42: V-CSF = 86.7+0.75*L-CSF, T-tau: V-CSF = 86.9+0.62*L-CSF, P-tau181: V-CSF = 2.6+0.74*L-CSF). CONCLUSION: Aβ 42, T-tau, and P-tau181 correlate linearly in-between V- and L-CSF, even stronger after CSF shunt surgery. Equations presented here, provide a novel tool to use V-CSF for diagnostic and prognostic entities relying on the L-CSF concentrations and can be applicable to clinical use when L-CSF samples are not available or less invasively obtained shunt reservoir samples should be interpreted

Corner Script : Tag-kirjaintyypin luominen

Tämän toiminnallisen opinnäytetyön projektiosuutena oli graffitikirjaintyypin suunnittelu. Lopullinen suunnittelu sisältää suur- ja pienaakkosista kirjaimet a−ö eli niin sanotut suomalaiset aakkoset. Lisäksi mukana ovat tarvittavat merkit sekä useita eri ligatuureja, eli kahden kirjaimen yhdistelmiä. Graffitin henkeen kuuluu, että kaikki yhden sanan samat kirjaimet eivät ole täysin samanlaisia toistensa kanssa, joten mukana on myös muutamia lisäkirjaimia täyttämään tämän tarpeen ja luomaan vaihtelua. Projektin tavoitteena oli luoda tag-kirjaintyyppi, joka on uskottavaa graffitia, mutta samalla myös selkeästi luettavaa ja ymmärrettävää myös graffitiin vihkiytymättömälle. Tutkimusosuus tarkastelee graffitin syntyä, sen alulle laittajia sekä syitä jotka ovat johtaneet graffitin kehitykseen pienistä puumerkeistä maailmanlaajuiseksi ilmiöksi. Työ erittelee lyhyesti myös graffititaiteen eri osa-alueet ja tyylit. Lisäksi tarkastelen kuvien kautta graffitihenkisten kirjaintyyppien käyttöä nykypäivänä. Toiminnallisessa osuudessa käyn läpi muotoiluprosessin sekä työvaiheet, jotka kävin läpi päästäkseni lopputulokseen. Työ esitellään ensimmäisistä hahmotelmista kirjainten muotoiluun ja digitalisointiin. Lopputuloksena syntyi Corner Script -kirjaintyyppi, jota voidaan käyttää erilaisissa kaupallisissa tarkoituksissa lehtien grafiikasta mainontaan ja keikkajulisteisiin, tai vaikkapa vaatteiden painatuksiin. Corner Script haastaa markkinoilla olevat tag-kirjaintyypit selkeydellään sekä luettavuudellaan pysymällä silti uskollisena graffitiperimälleen.The objective of the Thesis was to design a graffiti inspired typeface, a typeface that would be authentic graffiti, yet readable and understandable for those who are not familiar with graffiti, its letters and styles. The different phases of the process that lead to the final typeface were described and analyzed in detail. The birth of graffiti was examined, its originators and the reasons that led to its development to a world wide phenomenon. The different styles and aspects of graffiti art were kept separate. The usage of graffiti inspired typefaces today were also studied through pictures. The final design includes both upper and lower case letters from a to ö, namely the so called Finnish alphabet. In addition to the basic alphabet, all the basic glyphs, a few selected ligatures and a selection of extra letters to showcase the variability in letters, typical to graffiti writing are included. The result of the project is a tag display typeface that can be used in various commercial purposes such as posters, advertising, magazines and street fashion labels. The Corner Script typeface challenges the existing graffiti style typefaces by being clean and readable, yet remaining faithful to its origins in graffiti writing and tagging

”TUNTUU, ET TOI ON SAMALLA PUOLELLA” : asiantuntijoiden johtaminen jaetun johtamisen näkökulmasta Hippo terapiaklinikka Oy:ssä

Sosiaali- ja terveysalan muuttuvassa toimintaympäristössä tutkimuksellinen kehittäminen on nähty tarpeelliseksi. Sote-alan johtajilta ja esihenkilöiltä vaaditaan monipuolisia johtamiskykyjä, jotka vastaavat terveydenhuoltoympäristön monimutkaisuutta. Tämän tutkimuksen tarkoitus oli selvittää, miten kuntoutus- ja terveydenhoitohenkilöstön asiantuntijatyöskentelyä voidaan Hippo terapiaklinikka Oy:n toiminnassa tukea ja kehittää. Tutkimuksen tavoitteena oli tarjota näkökulmia työympäristön, toimintatapojen ja johtamisen kehittämiseksi. Tutkimuksella tuotetaan tietoa asiantuntijoiden ja esihenkilöiden käytettäväksi yrityksen kehitystyössä. Tämän opinnäytetyön tutkimusmetodiksi valikoitui teemahaastattelu, jonka avulla voidaan tutkimusongelmaa lähestyä monista eri suunnista. Tutkimuksessa haettiin vastausta kahteen kysymykseen, jotka kietoutuvat niin esihenkilöiden kuin asiantuntijoiden kokemuksiin. Näin ollen aineisto luonnollisesti rajautuu tutkimuksen näkökulman informanttien mukaan: esihenkilöt ja asiantuntijat. Haastattelut toteutettiin etäyhteyksin, joka mahdollisti osallistumisen maantieteellisestä sijainnista huolimatta. Opinnäytetyössä haastatteluaineistoa käsiteltiin teemoittelua hyödyntävän sisällön analyysin avulla. Aineisto luokiteltiin teema-alueittain esihenkilöiden ja asiantuntijoiden aineistoihin, joista se yhdistettiin esille nouseviin teemoihin. Lopulta teemat yhdistettiin kokonaisuuksiksi, josta voidaan tehdä tulkintaa ja hahmottaa ilmiötä valitusta teoreettista näkökulmasta. Aineistosta tulkittiin työskentelyä tukevia ja kehitettäviä osa-alueita. Teema-alueittain asiantuntijuutta ja työn tekemistä tukevia näkökulmia esiintyi kaikilla osa-alueilla. Tulosten perusteellä jaetun johtamisen hyödyntämiselle oli hyvät lähtökohdat, mutta toimintamallin hyödyntäminen vaatii kirkastamista, suunnitelmallisuutta ja terävöittämistä. Kehitysehdotukset tutkimuksen perusteella olivat strategisen työn kehittäminen ja asiantuntijoiden osallistaminen, esihenkilöiden koulutus, perehdyttäminen, ammatilliset tiimit ja ryhmätyöskentely sekä tiedon jakaminen ja hallinta. Esimerkiksi strategiatyössä voisi olla perusteltua vahvistaa ydinosaamisen ja asiantuntijuuden hyödyntämistä. Tutkimuksesta nousi jatkotutkimusaiheina kehitystyönä tehtävä strategisen työn kehittäminen, jonka lisäksi kansallisella tasolla jaetun johtamisen hyödyntämistä voidaan tutkia monissa sosiaali- ja terveysalan toimintaympäristöissä

Allu-alkuhaastattelu : Tietokonepohjainen tiedonkeruumenetelmä

Tiivistelmä Opinnäytetyön tarkoituksena oli luoda tietokonepohjainen haastattelumenetelmä toimintaterapeuttien työvälineeksi tehostamaan ensimmäistä toimintaterapeutin ja asiakkaan kohtaamista. Allu-alkuhaastatteluohjelma on toiminnallisen opinnäytetyön tuote. Allu-alkuhaastatteluohjelma kokoaa asiakkaan vastaukset yhteen ja tekee niistä yhteenvedon, joka on käytettävissä terapian suunnitteluun ja kirjaamisen tueksi. Ohjelman käytettävyyttä toimintaterapiassa arvioitiin käyttökokeilun pe-rusteella. Opinnäytetyö perustuu asiakaskeskeiseen lähestymistapaan, jota tukee toimintaterapian yleinen käsitteistö. Lisäksi kuvataan itsearvioinnin käytettävyyttä toimintaterapian tutkimusmenetelmänä. Ohjelma on suunniteltu näyttöön perustuvan kuntoutuksen laatuvaatimusten mukaan. Allu-alkuhaastatteluohjelman sisältämä haastattelurunko on luotu käyttäen toimintaterapiassa yleisesti käytössä olevaa viitekehystä, inhimillisen toiminnan mallia. Inhimillisen toiminnan mallin mukaan on tehty muita tutkittuja itsearviointiin ja asiakaskeskeiseen lähestymistapaan perustuvia arviointi- ja tutkimusmenetelmiä. Allu-alkuhaastatteluohjelmaa voidaan siten verrata jo olemassa oleviin arviointimenetelmiin. Opinnäytetyön haastatteluohjelman teknisen toteutuksen on tehnyt Kuopion yliopiston tietojenkäsittelytieteen opiskelija Pauli Siirama. Kokeiluversiota ei ole rajattu koskemaan tiettyä asiakasryhmää. Opinnäytetyö sisältää ohjelman käyttökokeilun arvioinnin, josta saadun palautteen perusteella ohjelmasta on tehty päätelmiä jatkokehitystä varten. Käyttökokeiluun osallistui kolme toimintate-rapeuttia ja kaksi ohjelmistosuunnittelijaa. Käyttökokeilijoiden palautteiden perusteella ohjelma sopii tietyiltä osin toimintaterapeutin työvälineeksi, mutta laajamittaisen käyttöönoton mahdollistamiseksi ohjelma vaatii muutoksia. Mahdollinen kehityskohde oli esimerkiksi ohjelman rakenteen tarkentaminen yleisesti terveydenhoitoalalla olevien kirjausmenetelmien mukaiseksi, joita ohjaavat ICD-10 ja ICF luokitukset. Lisäksi ohjelman sisältämien ohjeiden tarkentaminen on saadun palautteen perusteella yksi kehitettävä osa-alue. Allu-alkuhaastatteluohjelma täyttää sille asetetut tavoitteet ja on opinnäytetyön tarkoituksen mukaisesti työelämäsuuntautunut.Abstract: ‘Allu’ initial interviewing program is a product of functionality-orientated thesis. the purpose of thesis was to create a computer based interviewing method. The program is designed as a tool for occupational therapists to enhance the first meeting between the occupational therapist and the client. ‘Allu’ initial interviewing program collects the client´s answers and drafts a summary, which enables therapy intervention planning and supports documentation of information relevant throughout the course of the therapy. The functionality of the program in occupational therapy was intended to be assessed by its application in practice. The thesis is based on a client-centered approach, which is supported by the common concepts of occupational therapy. Moreover, it illustrates reasons for using self-assessment as a research tool in occupational therapy. The interviewing program has been created through the use of the central concepts used in occupational therapy, Model of Human Conduct. This model has been used as the basis for various studies within the field, which focus on self-assessment and a client centered approach as the method of evaluation and research. The existence of other evaluation methods enables comparison between the program and other established methods in the field. The technical specifications of the thesis initial interviewing program have been created by Pauli Siirama, a Computer Science student at Kuopio University. The trial version of the program has not been limited to a specific client group. The thesis contains findings on the test usage of the program. Hence the feedback received will act as the basis for analysis and suggestions for further development. Both occupational therapists and software programmers took part in the test usage of the program. Based on the feedback from the participants of the test use, the program is useable in certain areas as tool for occupational therapists. However, broader scale usage of the program requires modifications. A potential focus for further development is to mainstream the program structure to comply with the existing methods of documentation in the field of healthcare, which are guided by ICD -10 and ICF classifications. Another area of further development identified, based on the feedback received, is improved focus of the instructions contained within the program. ‘Allu’ initial interviewing program fulfills the aims set and is deemed as working life-orientated in accordance to the objectives of the thesis

Elevated CSF LRG and Decreased Alzheimer's Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer's disease (AD) pathology among the iNPH patients. CSF LRG, A beta(1-42), P-tau(181), and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p <0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., A beta(1-42), T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (Peer reviewe

Neuropathological findings in possible normal pressure hydrocephalus : A post-mortem study of 29 cases with lifelines

Publisher Copyright: © 2022, University of Muenster. All rights reserved.Aims: There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. Methods: We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Premortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. Results: The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer’s disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). Conclusions: We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of “hydrocephalic dementia” as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.Peer reviewe

Cerebrospinal Fluid Diagnostics of Alzheimer's Disease in Patients with Idiopathic Normal Pressure Hydrocephalus

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers.Objective: Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value.Methods: Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals (n = 33) and patients with diagnosed AD and no iNPH (n = 39).Results: Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*A beta(1-42), 0.779*t-Tau, and 0.610*P-Tau181) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau(181) to A beta(1-42) was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824).Conclusion: Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau(181)/A beta(1-42) ratio showed some utility in the diagnosis of AD in iNPH patients.Peer reviewe

Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer’s disease (AD) pathology among the iNPH patients. CSF LRG, Aβ1-42, P-tau181, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls