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Sökning: WFRF:(Wikkelsö Carsten 1947)

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1.
  • Edsbagge, Mikael, et al. (författare)
  • Spinal CSF absorption in healthy individuals.
  • 2004
  • Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study examines the extent of spinal cerebrospinal fluid (CSF) absorption in healthy individuals in relation to physical activity, CSF production, intracranial pressure (ICP), and spinal CSF movement. Thirty-four healthy individuals aged 21-35 yr were examined by lumbar puncture and radionuclide cisternography with repeated imaging. ICP was registered before and after CSF drainage, and CSF production was calculated. Spinal CSF absorption was calculated as reduction in spinal radionuclide activity. The radionuclide activity in the spinal subarachnoidal space was gradually decreased by 20 +/- 13% (mean +/- SD) during 1 h. The reduction was higher in active than in resting individuals (27 +/- 12% vs. 13 +/- 9%). The mean ICP in 19 of the individuals was 13.6 +/- 3.1 cm H(2)O. B-waves were found in 79% of the individuals, with a mean frequency of 0.6 +/- 0.3 min(-1). The mean CSF production rate was 0.34 +/- 0.13 ml/min. There were no correlations between radionuclide reduction, spinal movement of the radionuclide, and CSF production rate. The spinal radionuclide reduction found in this study indicates a spinal CSF absorption of 0.11-0.23 ml/min, more pronounced in active than in resting individuals.
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2.
  • Rabiei, Katrin, 1979, et al. (författare)
  • Diverse arachnoid cyst morphology indicates different pathophysiological origins
  • 2014
  • Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background There are few, limited, and to some extent contradictory, reports on the cellular and subcellular morphology of arachnoid cysts. In the literature cyst membranes are described as similar to, or as vastly different from, normal arachnoid membranes. Methods This paper reports electron microscopic analyses of symptomatic cysts from 24 patients (12 males and 12 females; age 10–79), that underwent fenestration surgery. Fourteen cysts were located in the middle cranial fossa (temporal), one in the interpeduncular cistern, five in the posterior fossa, and four were overlying the frontal cortex. Results Microscopic findings confirmed the diverse nature of this clinical condition. Twelve cyst walls resembled normal arachnoid, four had a conspicuous core of dense fibrous tissue with a simple epithelial lining, and the remaining aberrant cysts exhibited non-arachnoid luminal epithelia with plentiful microvilli and/or cilia, and also nervous tissue components in the wall. The possible identity and origin of various cyst types are discussed. We hypothesize that cysts are formed mostly at an early stage of embryonic development, as a teratological event. Conclusions Cysts with various epithelial linings and extracellular components most likely have different barrier properties and fluid turnover characteristics. Further studies are needed to elucidate relations between cyst morphology, fluid composition, pathogenesis, and clinical behaviour including growth rate and relapse tendency.
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3.
  • Agerskov, Simon, et al. (författare)
  • Absence of Disproportionately Enlarged Subarachnoid Space Hydrocephalus, a Sharp Callosal Angle, or Other Morphologic MRI Markers Should Not Be Used to Exclude Patients with Idiopathic Normal Pressure Hydrocephalus from Shunt Surgery
  • 2019
  • Ingår i: American Journal of Neuroradiology. - 0195-6108. ; 40:1, s. 74-79
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Several studies have evaluated the use of MR imaging markers for the prediction of outcome after shunt surgery in idiopathic normal pressure hydrocephalus with conflicting results. Our aim was to investigate the predictive value of a number of earlier proposed morphologic MR imaging markers in a large group of patients with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: One hundred sixty-eight patients (mean age, 70 +/- 9.3 years) with idiopathic normal pressure hydrocephalus, subjected to standardized quantification of clinical symptoms before and after shunt surgery, were included in the study. Outcome was calculated using a composite score. Preoperative T1, FLAIR, and flow-sensitive images were analyzed regarding the presence of 13 different morphologic MR imaging markers. RESULTS: The median Evans index was 0.41 (interquartile range, 0.37-0.44). All patients had an aqueductal flow void sign present and white matter hyperintensities. The median callosal angle was 68.8 degrees (interquartile range, 57.7 degrees-80.8 degrees). Dilated Sylvian fissures were found in 69%; focally dilated sulci, in 25%; and widening of the interhemispheric fissure, in 55%. Obliteration of the sulci at the convexity was found in 36%, and 36% of patients were characterized as having disproportionately enlarged subarachnoid space hydrocephalus. Sixty-eight percent of patients improved after surgery. None of the investigated MR imaging markers were significant predictors of improvement after shunt surgery. CONCLUSIONS: Disproportionately enlarged subarachnoid space hydrocephalus, a small callosal angle, and the other MR imaging markers evaluated in this study should not be used to exclude patients from shunt surgery. These markers, though they may be indicative of idiopathic normal pressure hydrocephalus, do not seem to be a part of the mechanisms connected to the reversibility of the syndrome.
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4.
  • Agerskov, Simon, et al. (författare)
  • MRI diffusion and perfusion alterations in the mesencephalon and pons as markers of disease and symptom reversibility in idiopathic normal pressure hydrocephalus
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. Methods Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3-6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. Results There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (r(s)= 0.80, p = 0.031 and r(s)= 0.66, p = 0.021, respectively). Conclusion The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH.
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5.
  • Agerskov, Simon, et al. (författare)
  • The phenotype of idiopathic normal pressure hydrocephalus-a single center study of 429 patients
  • 2018
  • Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X. ; 391, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Idiopathic Normal Pressure Hydrocephlaus (iNPH) is, despite a vastly improved knowledge of the disorder since its first description still underdiagnosed and undertreated. Because of this, there is a need for further large studies describing the typical symptomatology and reversibility of symptoms in iNPH, which was the aim of this study. Methods In all, 429 patients (mean age 71years) were included. Detailed pre- and postoperative examinations of symptoms and signs were analyzed. A composite outcome measure was constructed. Results Sixty-eight % improved after surgery. Preoperatively, 72% exhibited symptoms from three or four of the assessed domains (gait, balance, neuropsychology and continence) while 41% had symptoms from all four domains. Ninety % had gait disturbances, of which 75% had broad-based gait, 65% shuffling gait and 30% freezing of gait. These disturbances coexisted in most patients preoperatively, but were more likely to appear as isolated findings after surgery. Impaired balance was seen in 53% and retropulsion in 46%. MMSE <25 was seen in 53% and impaired continence in 86%. Improvements were seen in all symptom domains postoperatively. Conclusions The iNPH phenotype is characterized by a disturbance in at least 3/4 symptom domains in most patients, with improvements in all domains after shunt surgery. Most patients present with a broad-based and shuffling gait as well as paratonia. Present symptoms in all domains and a shuffling gait at the time of diagnosis seem to predict a favorable postoperative outcome, whereas symptom severity does not.
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6.
  • Anckarsäter, Henrik, 1966, et al. (författare)
  • Persistent regional frontotemporal hypoactivity in violent offenders at follow-up.
  • 2007
  • Ingår i: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 0925-4927 .- 1872-7123. ; 156:1, s. 87-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Since cross-sectional brain-imaging studies demonstrating frontotemporal cerebral hypoactivity in violent offenders have generally been carried out around the time of trial and sentencing, the findings might be influenced by the stressful situation of the subjects. It seems that no group of offenders with this finding has yet been followed longitudinally. We have re-examined nine offenders convicted of lethal or near-lethal violence in whom single photon emission tomography (SPECT) previously had demonstrated frontotemporal hypoperfusion. The mean interval between the initial and the follow-up examination was 4 years. The initially observed hypoactivity was found to have remained virtually unchanged at follow-up: no mean change in the group exceeded 5% in 12 assessed regions of interest. Although preliminary due to the small sample size, this study suggests that frontotemporal brain hypoactivity is a trait rather than a state in perpetrators of severe violent crimes.
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7.
  • Andrén, Kerstin, 1980, et al. (författare)
  • Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus
  • 2021
  • Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:4, s. 1153-1159
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed. Methods In 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPH(Delayed) (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPH(Early) (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders. Results Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPH(Delayed) compared to 10.1% in iNPH(Early) (p = 0.001). The adjusted hazard ratio in iNPH(Delayed) was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPH(Delayed) but in 4/16 cases in iNPH(Early) (p = 0.044). Conclusions The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
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8.
  • Andrén, Kerstin, 1980, et al. (författare)
  • Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study
  • 2018
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 265:1, s. 178-186
  • Tidskriftsartikel (refereegranskat)abstract
    • There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH). To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2-6 years after shunt surgery. We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004-2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR. On the smRS, 40% (38-41) of the patients were improved 2-6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2-6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2-6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS. This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.
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9.
  • Andrén, Kerstin, 1980, et al. (författare)
  • Natural course of idiopathic normal pressure hydrocephalus
  • 2014
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050. ; 2014:85, s. 806-810
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objectives The natural course of idiopathic normal pressure hydrocephalus (iNPH) has not been thoroughly studied. The consequences of postponing shunt treatment are largely unknown. We aimed to describe the effects of waiting for more than 6months before surgery and to compare the outcome with that seen in patients who waited for less than 3months. Methods 33 patients (iNPHDelayed) underwent an initial investigation (Pre-op 1), followed by re-examination, just prior to surgery, after waiting for at least 6months (Pre-op 2). Outcome was evaluated after 3months of treatment. 69 patients who were surgically treated within 3months after Pre-op 1 and who were also evaluated after 3months of treatment constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH scale and the modified Rankin Scale (mRS). iNPHDelayed patients were prospectively studied with regard to outcome, whereas the comparison group iNPHEarly was defined and analysed retrospectively. Results iNPHDelayed patients deteriorated significantly during their wait for surgery, with progression of symptom severity ranging from +7 to −47 on the iNPH scale, and from 0 to +3 on the mRS (both p<0.001). The magnitude of change after surgery was similar in the groups, but since the symptoms of iNPHDelayed patients had worsened while waiting, their final outcome was significantly poorer. Conclusions The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible. To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis.
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10.
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11.
  • Andrén, Kerstin, 1980, et al. (författare)
  • Survival in treated idiopathic normal pressure hydrocephalus
  • 2020
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 640-648
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome. Methods All 979 patients operated for iNPH 2004-2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls. Results At a median 5.9 (IQR 4.2-8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61-2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system. Conclusions Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.
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12.
  • Andrén, Kerstin, 1980, et al. (författare)
  • Symptoms and signs did not predict outcome after surgery: a prospective study of 143 patients with idiopathic normal pressure hydrocephalus
  • 2024
  • Ingår i: JOURNAL OF NEUROLOGY. - : SPRINGER HEIDELBERG. - 0340-5354 .- 1432-1459.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH. MethodsA prospective observational study of consecutively included iNPH patients, who underwent neurological, physiotherapeutic and neuropsychological assessments before and after shunt surgery. The primary outcome measure was the total change on the iNPH scale, and patients were defined as improved postoperatively if they had improved by at least five points on that scale. Results143 iNPH patients were included, and 73% of those were improved after surgery. None of the examined symptoms or signs could predict which patients would improve after shunt surgery. A dominant subjective complaint of memory problems at baseline was predictive of non-improvement. The reported comorbidities, duration of symptoms and BMI were the same in improved and non-improved patients. Each of the symptom domains (gait, neuropsychology, balance, and continence) as well as the total iNPH scale score improved significantly (from median 53 to 69, p < 0.001). The proportions of patients with shuffling gait, broad-based gait, paratonic rigidity and retropulsion all decreased significantly. DiscussionThis study confirms that the recorded clinical signs, symptoms, and impairments in the adopted clinical tests are characteristic findings in iNPH, based on that most of them improved after shunt surgery. However, our clinical data did not enable predictions of whether patients would respond to shunt surgery, indicating that the phenotype is unrelated to the reversibility of the iNPH state and should mainly support diagnosis. Absence of specific signs should not be used to exclude patients from treatment.
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13.
  • Blomsterwall, Elisabeth, et al. (författare)
  • Postural disturbance in patients with normal pressure hydrocephalus.
  • 2000
  • Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 102:5, s. 284-91
  • Tidskriftsartikel (refereegranskat)abstract
    • The postural function in 52 patients with normal pressure hydrocephalus (NPH) and in 19 patients with subcortical arteriosclerotic encephalopathy (SAE) was analysed bedside and in 17 of the NPH, 10 of the SAE and 23 healthy individuals (HI) also examined with a force platform. At the bedside examination, no differences in postural functions between NPH and SAE patients were found. The NPH patients improved more in the postural than in motor functions after shunt surgery. The NPH patients had a larger sway area and a higher backward directed velocity of centre of pressure than HI. The direction of the inclination in the sagittal plane was neutral or forward in the NPH and the SAE patients while it was backward in HI. The postural function was better in positions with open eyes in all 3 groups, but significantly less in the NPH patients, indicating a misinterpretation of afferent visual stimuli in the brainstem postural centre.
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14.
  • Blomsterwall, Elisabeth, et al. (författare)
  • Postural function and subjective eye level in patients with idiopathic normal pressure hydrocephalus.
  • 2011
  • Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 258:7, s. 1341-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Disturbance of posture is a frequent indication of idiopathic normal pressure hydrocephalus (iNPH) and is characterised by an increased sway in the frontal and sagittal planes. Further, iNPH patients with increased backward sway are known to have a defective perception of the subjective visual vertical (SVV), with the upper portion of an articulated rod tilted towards themselves. The objective of the present study was to compare subjective eye level (SEL) with actual eye level (EL) and compare this data with SVV and postural function. Twenty iNPH patients and ten normal controls estimated SEL by placing an adjustable horizontal line at EL. Sway pattern and SVV were also examined as previously described. The patients presented larger errors on downward as compared to upward line adjustments; all patients also presented a SVV tilted towards them. The patients swayed more in the sagittal than in the frontal plane at a higher speed than the normal controls, and they were relatively less helped by their vision. This is in accordance with the tendency to fall backwards seen in many iNPH patients. iNPH patients have a tendency to place SEL higher than EL and this, together with examination of SVV and sway pattern, suggests defective internal processing of gravicentric information.
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15.
  • Bremell, Daniel, 1978, et al. (författare)
  • Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
  • 2013
  • Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited. Methods We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease. Results In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL. Conclusions We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
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16.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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17.
  • Constantinescu, Clara, 1995, et al. (författare)
  • Prevalence of Possible Idiopathic Normal Pressure Hydrocephalus in Sweden: A Population-Based MRI Study in 791 70-Year-Old Participants.
  • 2024
  • Ingår i: Neurology. - 1526-632X. ; 102:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the prevalence of iNPH and iNPH-specific radiologic changes and their association with clinical symptoms in a large, 70-year-old population-based cohort (Gothenburg H70).In this cross-sectional study, disturbances in gait and balance, cognition, and urinary continence were assessed using clinical examination and self-report. MRI was evaluated for iNPH-specific imaging markers. iNPH was diagnosed according to International Guidelines (I.G.). Based on radiologic findings, participants were allocated to 1 of 4 groups: (A) Evans index (EI) ≤0.3 (reference), (B) EI >0.3 without other iNPH-typical radiologic findings, (C) radiologically probable iNPH according to I.G., and (D) radiologically holistically probable (h-probable) iNPH fulfilling radiologic criteria according to I.G. plus highly iNPH-specific changes according to an experienced neuroradiologist.The Gothenburg H70 Studies include 791 individuals (377 men, 414 women) born in 1944 who underwent brain MRI. The prevalence of iNPH was 1.5% (2.1% for men, 0.96% for women) according to I.G. Ninety participants (11%) had EI >0.3 without other iNPH-typical radiologic findings, 29 (3.7%) fulfilled the I.G. radiologic probable iNPH criteria alone, and 11 (1.4%) were classified as radiologically h-probable iNPH. Forty participants (5.1%) had I.G. radiologic features of iNPH (70% men vs 30% women, p = 0.005). Gait disturbances were more common in participants with EI >0.3 without other radiologic iNPH features (B) (33%) compared with the reference group (A) (19%) (p = 0.006). All clinical symptoms were more common in participants with I.G. radiologic features of iNPH (C + D) than they were in the reference group (A) (p < 0.03).The iNPH prevalence of 1.5% among 70-year-olds, which is considerably higher than earlier reported in this age group, suggests that iNPH may be more common than previously assumed. This is supported by the 5.1% total prevalence of imaging signs of iNPH. Ventriculomegaly without other iNPH-typical radiologic findings may be an early sign of developing iNPH in some patients.
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18.
  • Constantinescu, Radu, 1966, et al. (författare)
  • Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
  • 2010
  • Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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19.
  • Curtis, Maurice A, et al. (författare)
  • Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension.
  • 2007
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 315:5816, s. 1243-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone cells reach the olfactory bulb (OB) in rodents. However, the RMS in the adult human brain has been elusive. We demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the OB, and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by magnetic resonance imaging, cell-specific markers, and electron microscopy, contains progenitor cells with migratory characteristics and cells that incorporate 5-bromo-2'-deoxyuridine and become mature neurons in the OB.
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20.
  • Edsbagge, Mikael, et al. (författare)
  • Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.
  • 2017
  • Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 58:3, s. 821-828
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively.To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals.CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years).Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed.These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.
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21.
  • Edsbagge, Mikael, et al. (författare)
  • Spinal cerebrospinal fluid volume in healthy elderly individuals.
  • 2011
  • Ingår i: Clinical anatomy (New York, N.Y.). - : Wiley. - 1098-2353 .- 0897-3806. ; 24:6, s. 733-40
  • Tidskriftsartikel (refereegranskat)abstract
    • The amount of spinal cerebrospinal fluid (CSF) could be of importance for the understanding of CSF dynamics, CSF biomarker analyses as well as for the amount and effect of anaesthesia using intrathecally administered drugs. However, knowledge of spinal CSF volumes is scarce. The main purpose of this article is to present data on spinal CSF volumes. In total, 22 healthy individuals aged between 64 and 76 years underwent MR imaging with a 3D balanced turbo field echo pulse sequence, which provided high contrast between spinal cord, CSF and the extradural surroundings. The entire spinal CSF volume, the cervical, thoracic, and lumbosacral CSF volumes and the spinal cord volume were calculated. The total spinal CSF volume was 81 ± 13 ml (range 52-103 ml). The amount of CSF in the cervical region was 19 ± 4 ml, in the thoracic region 38 ± 8 and in the lumbosacral region 25 ± 7 ml. There was no difference between genders nor was there any correlation with height. The volume of the spinal cord was 20 ± 3 ml. The results present new magnetic resonance imaging-based data on the spinal CSF volume in healthy elderly individuals. Clin. Anat. 24:733-740, 2011. © 2011 Wiley-Liss, Inc.
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22.
  • Farahmand, Dan, et al. (författare)
  • A double-blind randomized trial on the clinical effect of different shunt valve settings in idiopathic normal pressure hydrocephalus
  • 2016
  • Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 124:2, s. 359-367
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH). METHODS In this prospective double-blinded, randomized, controlled, double -center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20-4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6 -month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20-4 and 12) were compared for each clinical evaluation. RESULTS Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20-4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was-significant within the first 3 months, and thereafter no significant improvement was seen in either group. CONCLUSIONS Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.
  •  
23.
  • Farahmand, Dan, et al. (författare)
  • Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions
  • 2015
  • Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:2, s. 222-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt. Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus. Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm. Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg. Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.
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24.
  • Fasano, A., et al. (författare)
  • Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus
  • 2020
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:11, s. 1945-1954
  • Tidskriftsartikel (refereegranskat)abstract
    • Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology. (c) 2020 International Parkinson and Movement Disorder Society
  •  
25.
  • Feletti, A., et al. (författare)
  • Ventriculoperitoneal Shunt Complications in the European Idiopathic Normal Pressure Hydrocephalus Multicenter Study
  • 2019
  • Ingår i: Operative neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 2332-4260 .- 2332-4252. ; 17:1, s. 97-102
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Ventriculoperitoneal shunt (VP-shunt) is the standard of treatment for idiopathic normal pressure hydrocephalus (iNPH). However, a thorough investigation of VP-shunt complications in this population is lacking. OBJECTIVE: To present the analysis and the rates of complications progressively occurring during the first year after shunt surgery in the patients with iNPH included in the European multicenter (EU-iNPH) study. METHODS: Patients (n=142) were prospectively included in the EU-iNPH study by 13 institutions. All patients received a programmable VP-shunt. One hundred fifteen patients completed the 12-mo follow-up. Reexaminations were performed 1, 3, and 12 mo after surgery. Data regarding symptomatic over- or underdrainage, infections, malposition, subdural collections, and shunt surgery were collected and analyzed. RESULTS: Thirty patients (26%) experienced symptoms due to shunt underdrainage. Symptomatic overdrainage was reported in 10 (9%). Shunt adjustments were made in 43 (37%). Shunt malposition was recognized as the primary cause of shunt malfunction in 8 (7%), while only 1 infection (0.9%) occurred. Subdural hematoma was diagnosed in 7 (6%) and was treated by increasing the opening pressure of the valve in 5 patients. Hygroma was diagnosed in 10 (9%), requiring surgery in 1 patient. Overall, 17 patients (15%) underwent 19 shunt surgeries. CONCLUSION: The advances in valve technology, a careful opening pressure setting, and rigorous follow-up allow a significant reduction of complications, which can be usually managed nonsurgically within the first 3 to 6 mo. Copyright © 2018 by the Congress of Neurological Surgeons.
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