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  • 1.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, p. 1-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment. METHODS Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery. Patients underwent pre- and postoperative (3-month) clinical assessment with a modified iNPH scale. The preoperative CSF biomarkers and the levels of soluble and insoluble Aβ species in cortical biopsy samples were analyzed for their association with a favorable outcome following the VP shunt procedure, defined as a ≥ 5-point increase in the iNPH scale. RESULTS The brain tissue levels of Aβ42 were negatively correlated with CSF Aβ42 (Spearman's r = -0.53, p < 0.05). The Aβ40, Aβ42, and Aβ oligomer/protofibril levels in cortical biopsy samples were higher in patients with insoluble cortical Aβ aggregates (p < 0.05). The preoperative CSF Aβ42 levels were similar in patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at 3 months postsurgery. In contrast, the presence of cortical Aβ aggregates and high brain tissue Aβ42 levels were associated with a poor outcome following VP shunt treatment (p < 0.05). CONCLUSIONS Brain tissue measurements of soluble Aβ species are feasible. Since high Aβ42 levels in cortical biopsy samples obtained in patients with iNPH indicated a poor surgical outcome, tissue levels of Aβ species may be associated with the clinical response to shunt treatment.

  • 2.
    Kockum, Karin
    et al.
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Lilja-Lund, Otto
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Rosell, Michelle
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Söderström, Lars
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, Katarina
    Department of Pharmacology and Clinical Neuroscience, Neurology, Östersund, Umeå University, Umeå, Sweden.
    The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 3, p. 569-576Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Despite the important role of imaging in diagnosing idiopathic normal pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.

    METHODS: In this prospective, population based study of iNPH, 168 individuals (93 females, 75 males), mean age 75 years (range 66-92 years), underwent a computed tomography (CT) of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters i.e. Evans' index, callosal angle, size of temporal horns, narrow high convexity sulci, dilated Sylvian fissures, focally dilated sulci, periventricular hypodensities and bulging of the lateral ventricular roof.

    RESULTS: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total score of the iNPH Radscale and clinical symptoms. The interrater agreement for the included radiological parameters was high (ICC = 0.74-0.97).

    CONCLUSION: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms, should raise suspicion of iNPH motivating further evaluation for shunt-surgery.

  • 3.
    Shanks, J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bloch, K. Markenroth
    Lund Univ, Bioimaging Ctr, Lund, Sweden.
    Laurell, K.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Fahlström, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery2019In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 40, no 3, p. 453-459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 mu L; interquartile range, 69.8-142.8 mu L) compared with 62.5 mu L (interquartile range, 58.3-73.8 mu L; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 mu L (interquartile range, 81-241 mu L) to 88 mu L (interquartile range, 51.8-173.3 mu L; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

  • 4.
    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.

  • 5.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Laurell, K
    Department of Pharmacology and Clinical Neuroscience (K.L.), Unit of Neurology, Östersund, Umeå University, Umeå, Sweden.
    Ahlgren, A
    Department of Medical Radiation Physics (A.A.), Lund University, Lund, Sweden..
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arterial Spin-Labeling Perfusion MR Imaging Demonstrates Regional CBF Decrease in Idiopathic Normal Pressure Hydrocephalus2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 11, p. 2081-2088Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF.

    MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses.

    RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001).

    CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.

  • 6.
    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.

  • 7.
    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 hydrocephalus2019In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 130, no 1, p. 130-135Article 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.

  • 8.
    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.

  • 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. Department of Pharmacology and Clinical Neuroscience, Östersund, Umeå 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.
    Preoperative Prognostic Value of MRI Findings in 109 Patients with Idiopathic Normal Pressure HydrocephalusManuscript (preprint) (Other academic)
  • 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.

  • 11.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Levodopa-carbidopa enteral suspension in advanced Parkinson's disease: clinical evidence and experience2017In: Therapeutic advances in neurological disorders, ISSN 1756-2856, Vol. 10, no 3, p. 171-187Article, review/survey (Refereed)
    Abstract [en]

    The duration of action of oral levodopa becomes shorter as Parkinson's disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in 'off' time and 'on' time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.

  • 12.
    Virhammar, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Warntjes, M
    Laurell, K
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Quantitative MRI for Rapid and User-Independent Monitoring of Intracranial CSF Volume in Hydrocephalus2016In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 37, no 5, p. 797-801Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    Quantitative MR imaging allows segmentation of different tissue types and automatic calculation of intracranial volume, CSF volume, and brain parenchymal fraction. Brain parenchymal fraction is calculated as (intracranial volume - CSF volume) / intracranial volume. The purpose of this study was to evaluate whether the automatic calculation of intracranial CSF volume or brain parenchymal fraction could be used as an objective method to monitor volume changes in the ventricles.

    MATERIALS AND METHODS:

    A lumbar puncture with drainage of 40 mL of CSF was performed in 23 patients under evaluation for idiopathic normal pressure hydrocephalus. Quantitative MR imaging was performed twice within 1 hour before the lumbar puncture and was repeated 30 minutes, 4 hours, and 24 hours afterward. For each time point, the volume of the lateral ventricles was manually segmented and total intracranial CSF volume and brain parenchymal fraction were automatically calculated by using Synthetic MR postprocessing.

    RESULTS:

    At 30 minutes after the lumbar puncture, the volume of the lateral ventricles decreased by 5.6 ± 1.9 mL (P < .0001) and the total intracranial CSF volume decreased by 11.3 ± 5.6 mL (P < .001), while brain parenchymal fraction increased by 0.78% ± 0.41% (P < .001). Differences were significant for manual segmentation and brain parenchymal fraction even at 4 hours and 24 hours after the lumbar tap. There was a significant association using a linear mixed model between change in manually segmented ventricular volume and change in brain parenchymal fraction and total CSF volume, (P < .0001).

    CONCLUSIONS:

    Brain parenchymal fraction is provided rapidly and fully automatically with Synthetic MRI and can be used to monitor ventricular volume changes. The method may be useful for objective clinical monitoring of hydrocephalus.

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