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  • 1. Andersson, K.
    et al.
    Manchester, I. R.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cesarini, Kristina Giuliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Malm, J.
    Eklund, A.
    Measurement of CSF dynamics with oscillating pressure infusion2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Introduction Infusion tests are used to diagnose and select patients with idiopathic normal pressure hydrocephalus (INPH) for shunt surgery. The test characterizes cerebrospinal fluid dynamics and estimates parameters of the cerebrospinal fluid system, the pressure-volume index (PVI) and the outflow conductance (Cout). The Oscillating Pressure Infusion (OPI) method was developed to improve the test and reduce the investigation time. The aim of this study was to evaluate the new OPI method by comparing it with an established reference method. Methods Forty-seven patients (age 71.2 +/- 8.9years) with communicating hydrocephalus underwent a preoperative lumbar infusion investigation with two consecutive infusion protocols, reference (42min) and new (20min), that is, 94 infusion tests in total. The OPI method estimated Cout and PVI simultaneously. A real-time analysis of reliability was applied to investigate the possibility of infusion time reduction. Results The difference in Cout between the methods was 1.2 +/- 1.8l/s/kPa (Rout=-0.8 +/- 3.5mmHg/ml/min), P<0.05, n=47. With the reliability analysis, the preset 20min of active infusion could have been even further reduced for 19 patients to between 10 and 19min. PVI was estimated to 16.1 +/- 6.9ml, n=47. Conclusions The novel Oscillating Pressure Infusion method produced real-time estimates of Cout including estimates of reliability that was in good agreement with the reference method and allows for a reduced and individualized investigation time.

  • 2.
    Elobeid, Adila
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Laurell, Katarina
    Cesarini, Kristina Giuliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Correlations Between Mini-Mental State Examination Score, Cerebrospinal Fluid Biomarkers, and Pathology Observed in Brain Biopsies of Patients With Normal-Pressure Hydrocephalus2015In: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 74, no 5, p. 470-479Article in journal (Refereed)
    Abstract [en]

    Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A beta) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant A beta and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between A beta-immunostained area fraction in tissue and A beta 42 (42-amino-acid form of A beta) in cerebrospinal fluid (CSF). Levels of A beta 42 were significantly lower in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant A beta and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of A beta (A beta 42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.

  • 3.
    Libard, Sylwia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Laurell, Katarina
    Umeå Univ, Dept Pharmacol & Clin Neurosci, Östersund.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient with Idiopathic Normal Pressure Hydrocephalus2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 4, p. 1451-1461Article in journal (Refereed)
    Abstract [en]

    We had an opportunity to assess the change observed in the brain regarding Alzheimer’s disease (AD)-related alterations, cell count, and inflammation that took place during a period of 21 months in a subject with a definite diagnosis of AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers, i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4 HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR, ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein (GFAP); and AD-related markers, hyperphosphorylated τ (HPτ) and amyloid-β (Aβ, Aβ40, Aβ42) were assessed. Morphometrically assessed immunoreactivity of all neuronal and all microglial markers and Aβ42 decreased parallel with an increase in the HPτ in the frontal cortex. The expression of GFAP was stable with time. The first sample was obtained during the therapeutic shunting procedure for iNPH, and the second sample was obtained postmortem. Negligible reactive changes were observed surrounding the shunt channel. In conclusion, in the late stage of AD with time, a neuronal loss, increase in the HPτ, and decrease in Aβ42 and microglia was observed, whereas the expression of GFAP was rather stable. The observations described here suggest that when a brain biopsy has been obtained from an adult subject with iNPH, the assessment of postmortem brain is of major significance.

  • 4. Malm, J.
    et al.
    Sundstrom, N.
    Cesarini, Kristina G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Edsbagge, M.
    Kristensen, B.
    Leijon, G.
    Eklund, A.
    Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, no 3, p. 199-205Article in journal (Refereed)
    Abstract [en]

    Objectives: The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study.

    Methods: Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered.

    Results: Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Postinvestigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed.

    Conclusion: Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.

  • 5.
    Sundström, Nina
    et al.
    Umea Univ, Dept Radiat Sci, Biomed Engn, Umea, Sweden..
    Malm, Jan
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Laurell, Katarina
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Lundin, Fredrik
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Kahlon, Babar
    Univ Hosp, Dept Neurosurg, Lund, Sweden..
    Cesarini, Kristina G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Leijon, Göran
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Wikkelso, Carsten
    Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden..
    Incidence and outcome of surgery for adult hydrocephalus patients in Sweden2017In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 31, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Object: To present population-based and age related incidence of surgery and clinical outcome for adult patients operated for hydrocephalus, registered in the Swedish Hydrocephalus Quality Registry (SHQR). Methods: All patients registered in SHQR during 2004-2011 were included. Data on age, gender, type of hydrocephalus and type of surgery were extracted as well as three months outcome for patients with idiopathic normal pressure hydrocephalus (iNPH). Results: The material consisted of 2360 patients, 1229 men and 1131 women, age 63.8 +/- 14.4 years (mean standard deviation (SD)). The mean total incidence of surgery was 5.1 +/- 0.9 surgeries/100,000/year; 4.7 +/- 0.9 shunt surgeries and 0.4 +/- 0.1 endoscopic third ventriculostomies. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus, the incidence of surgery was 2.2 +/- 0.8, 1.9 +/- 0.3 and 0.8 +/- 0.1/100,000/year, respectively. During 2004-2011, the incidence of surgery increased in total (p = .044), especially in age groups 70-79 years and > 80 years (p = .012 and p = .031). After surgery, 253 of 652 iNPH patients (38.8%) improved at least one step on the modified Rankin scale (mRS). Number needed to treat was 3.0 for improving one patient from unfavourable (mRS 3-5) to favourable (mRS 0-2). The mean score of a modified iNPH scale increased from 54 +/- 23 preoperatively to 63 +/- 25 postoperatively (p < .0001, n = 704), and 58% improved. No significant regional differences in incidence, surgical techniques or outcome were found. Conclusions: Incidence of hydrocephalus surgery increased significantly during 2004-2011, specifically in elderly patients. Surgical treatment of INPH markedly improved functional independence, but the improvement rate was low compared to recent single- and multicentre studies. Thus, the potential for surgical improvement is likely lower than generally reported when treating patients as part of everyday clinical care.

  • 6.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    The CSF tap test in normal pressure hydrocephalus: evaluation time, reliability and the influence of pain2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 2, p. 271-276Article in journal (Refereed)
    Abstract [en]

    Background:  The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post-TT.

    Methods:  Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale.

    Results:  Twenty-seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post-TT. The variability between two measurements was low (Intra class correlation coefficient = 0.97), and the inter-rater agreement was good with a κ = 0.74. Pain correlated negatively with improvement in gait speed (r = -0.40, P < 0.05).

    Conclusions:  We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post-lumbar puncture pain negatively affects the gait and should be minimized.

  • 7.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Department of Pharmacology and Clinical Neuroscience, Östersund, Umeå University.
    Ahlgren, André
    Department of Medical Radiation Physics, Lund University.
    Cesarini, Kristina Giuliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal2014In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 34, no 11, p. 1771-1778Article in journal (Refereed)
    Abstract [en]

    Pseudo-continuous arterial, spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.

  • 8.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Umeå University, Umeå, Sweden.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Increase in callosal angle and decrease in ventricular volume after shunt surgery in patients with idiopathic normal pressure hydrocephalus.2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, p. 1-6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Postoperative decrease in ventricle size is usually not detectable either by visual assessment or by measuring the Evans index in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of the present study was to investigate whether the angle between the lateral ventricles (the callosal angle [CA]) increases and ventricular volume decreases after shunt surgery in patients with iNPH. METHODS Magnetic resonance imaging of the brain was performed before and 3 months after shunt surgery in 18 patients with iNPH. The CA and Evans index were measured on T1-weighted 3D MR images, and ventricular volume contralateral to the shunt valve was measured with quantitative MRI. RESULTS The CA was larger postoperatively (mean 78°, 95% CI 69°-87°) than preoperatively (mean 67°, 95% CI 60°-73°; p < 0.001). The volume of the lateral ventricle contralateral to the shunt valve decreased from 73 ml (95% CI 66-80 ml) preoperatively to 63 ml (95% CI 54-72 ml) postoperatively (p < 0.001). The Evans index was 0.365 (95% CI 0.35-0.38) preoperatively and 0.358 (95% CI 0.34-0.38) postoperatively (p < 0.05). Postoperative change of CA showed a negative correlation with change of ventricular volume (r = -0.76, p < 0.01). CONCLUSIONS In this sample of patients with iNPH, the CA increased and ventricular volume decreased after shunt surgery. The relative difference was most pronounced for the CA, indicating that this accessible, noninvasive radiological marker should be evaluated further as an indirect method to determine shunt function in patients with iNPH.

  • 9.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Preoperative Prognostic Value of MRI Findings in 108 Patients with Idiopathic Normal Pressure Hydrocephalus2014In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 35, no 12, p. 2311-2318Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    MR imaging is used in the diagnostic evaluation of patients with idiopathic normal pressure hydrocephalus. The aim of this study was to describe the prevalence of several imaging features and their prognostic use in the selection of shunt candidates with idiopathic normal pressure hydrocephalus.

    MATERIALS AND METHODS:

    Preoperative MR imaging scans of the brain were retrospectively evaluated in 108 patients with idiopathic normal pressure hydrocephalus who had undergone a standardized, clinical evaluation before and 12 months after shunt surgery. The MR imaging features investigated were the Evans index, callosal angle, narrow sulci at the high convexity, dilation of the Sylvian fissure, diameters of the third ventricle and temporal horns, disproportionately enlarged subarachnoid space hydrocephalus, flow void through the aqueduct, focal bulging of the roof of the lateral ventricles, deep white matter hyperintensities, periventricular hyperintensities, and focal widening of sulci and aqueductal stenosis.

    RESULTS:

    In logistic regression models, with shunt outcome as a dependent variable, the ORs for the independent variables, callosal angle, disproportionately enlarged subarachnoid space hydrocephalus, and temporal horns, were significant (P < .05), both in univariate analyses and when adjusted for age, sex, and previous stroke.

    CONCLUSIONS:

    A small callosal angle, wide temporal horns, and occurrence of disproportionately enlarged subarachnoid space hydrocephalus are common in patients with idiopathic normal pressure hydrocephalus and were significant predictors of a positive shunt outcome. These noninvasive and easily assessed radiologic markers could aid in the selection of candidates for shunt surgery.

  • 10.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Cesarini, Kristina Giuliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus2014In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, no 1, p. 178-184Article in journal (Refereed)
    Abstract [en]

    Object

    Different neuroimaging biomarkers have been studied to find a tool for prediction of response to CSF shunting in idiopathic normal-pressure hydrocephalus (iNPH). The callosal angle (CA) has been described as useful in discriminating iNPH from ventricular dilation secondary to atrophy. However, the usefulness of the CA as a prognostic tool for the selection of shunt candidates among patients with iNPH is unclear. The aim of this study was to compare the CA in shunt responders with that in nonresponders and clarify whether the CA can serve as a predictor of the outcome.

    Methods

    Preoperative MRI brain scans were evaluated in 109 patients who had undergone shunt surgery for iNPH during 2006-2010. Multiplanar reconstruction was performed interactively to obtain a coronal image through the posterior commissure, perpendicular to the anterior-posterior commissure plane. The CA was measured as the angle between the lateral ventricles on the coronal image. The patients were examined clinically before surgery and at 12 months postoperatively.

    Results

    Shunt responders had a significantly smaller mean preoperative CA compared with nonresponders: 59° (95% CI 56°-63°) versus 68° (95% CI 61°-75°) (p < 0.05). A CA cutoff value of 63° showed the best prognostic accuracy.

    Conclusions

    The preoperative CA is smaller in patients whose condition improves after shunt surgery and may be a useful tool in the selection of shunt candidates among patients with iNPH.

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