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  • 1. Alfstad, K Å
    et al.
    Lossius, M I
    Røste, G K
    Mowinckel, P
    Scheie, D
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Dept. of Laboratory medicine/Pathology, Umeå University, Umeå Sweden.
    Larsson, P G
    Nakken, K O
    Acute postoperative seizures after epilepsy surgery: a long-term outcome predictor?2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The prognostic value of acute postoperative seizures (APS) after epilepsy surgery is much debated. This study evaluated APS, defined as seizures in the first week post-surgery, as a predictor of long-term seizure outcome, and investigated the utility of other potential outcome predictors.

    MATERIALS AND METHODS: Medical records of 48 patients with temporal and extra-temporal epilepsy surgery were studied. Forty patients had lesional surgery. All had at least 2 year postoperative follow-up.

    RESULTS: At 2 year follow-up, 25 patients (53%) were seizure free. Univariate analysis showed that APS (P = 0.048), using ≥ six AEDs prior to surgery (P = 0.03), pathological postoperative EEG (P = 0.043) and female gender (P = 0.012) were associated with seizure recurrence.

    CONCLUSIONS: Univariate analysis indicate that APS, a high number of AEDs used prior to surgery, and pathological postoperative EEG are possible predictors of seizure recurrence after epilepsy surgery. Only gender retained significance in the multivariate analysis.

  • 2. Anckarsäter, R.
    et al.
    Vasic, N.
    Jidéus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Kristiansson, M.
    Zetterberg, H.
    Blennow, K.
    Anckarsäter, H.
    Cerebrospinal fluid protein reactions during non-neurological surgery2007In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 115, no 4, p. 254-259Article in journal (Refereed)
    Abstract [en]

    Objective - To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. Subjects and methods - Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. Results - Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (β2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (βTP) remained unchanged. Conclusions - Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.

  • 3. 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.

  • 4. Appelros, P.
    et al.
    Gunnarsson, K. E.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ten-year risk for myocardial infarction in patients with first-ever stroke: a community-based study2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 6, p. 383-389Article in journal (Refereed)
    Abstract [en]

    Background: Stroke and coronary heart disease (CHD) share common risk factors. The risk for stroke patients to have a myocardial infarction (MI) has not been fully explored.

    Methods: Three hundred and seventy-seven first-ever stroke patients were ascertained prospectively. The 10-year incidence of MI was examined by register searches. The results were compared to the general Swedish population. Predictors for MI were identified using univariate and multivariate analysis.

    Results: The cumulative incidence of MI over 10 years was 25.0/100 (95% confidence interval (CI), 19.5-31.5), 26.5 for men, (95% CI, 18.9-45.8) and 23.4 for women (95% CI, 16.0-32.9). Compared to the general population, the relative risk for stroke patients having a MI was 1.6 for men (95% CI, 1.12-2.37) and 1.9 for women (95% CI, 1.27-2.90). In multivariate analysis, CHD before the stroke (MI, angina pectoris, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty) and peripheral artery disease were significant predictors for MI.

    Conclusions: The risk for MI is significantly higher, for both male and female stroke patients, compared to the general population. Stroke patients with previous CHD and peripheral artery disease are at highest risk. Stroke patients should receive adequate secondary prevention, and cardiac complaints must be taken seriously.

  • 5. Appelros, P.
    et al.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Validation of the Swedish inpatient and cause-of-death registers in the context of stroke2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 4, p. 289-293Article in journal (Other academic)
    Abstract [en]

    Background - Quality follow-up within stroke care is important in times when stroke prevalence is increasing and health care funds are limited. Administrative data, such as data from the inpatient register (IPR) and the cause-of-death register (CDR) are often used for this purpose, but the validity of such data has not been ascertained. Methods - During the year 1999-2000, a community-based stroke register was established in a Swedish municipality. Data from that register was compared with two administrative registers, the IPR and the CDR. Results - Using multiple overlapping data sources, 377 patients with first-ever stroke were found in the community-based register. Forty-four of these (12%) were missing in the IPR/CDR. Non-hospitalized patients were less likely to be registered in the IPR/CDR, as were patients who were not initially treated in a stroke unit. Stroke severity was lower among non-registered patients. Thirty patients (8%) in the IPR/CDR were misclassified as stroke patients. Conclusions - Quality follow-up within stroke care could be biased or have low comparability, when administrative data are used. Great caution should be taken when data derived from the inpatient and cause-of-death registers, and more validation work needs to be carried out in the context of stroke.

  • 6. Appelros, Peter
    et al.
    Stegmayr, B.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    A review on sex differences in stroke treatment and outcome2010In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 121, no 6, p. 359-369Article, review/survey (Refereed)
    Abstract [en]

    Background - Beyond epidemiological differences, it has been controversial whether any important sex differences exist in the treatment of stroke. In this review paper, the following areas are covered: thrombolysis, stroke unit care, secondary prevention, surgical treatment, and rehabilitation. Additionally, symptoms at stroke onset, as well as outcome measures, such as death, dependency, stroke recurrence, quality of life, and depression are reviewed. Methods - Search in PubMed, tables-of-contents, review articles, and reference lists after studies that include information about sex differences in stroke care. Results - Ninety papers are included in this review. Women suffer more from cortical and non-traditional symptoms. Men and women benefit equally from thrombolysis and stroke unit care. Women with cardioembolic strokes may benefit more from anticoagulant therapy. Most studies have not found any tendency towards sexism in the choice of treatment. Post-stroke depression and low quality-of-life seem to be more common among women. Mortality rates are higher among men in some studies, while long-term ADL-dependency seems to be more common among women. Conclusions - Sex differences in stroke treatment and outcome are small, with no unequivocal proof of sex discrimination. Women have less favourable functional outcome because of higher age at stroke onset and more severe strokes.

  • 7. Archer, T.
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Johansson, B.
    Exercise alleviates Parkinsonism: clinical and laboratory evidence2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 2, p. 73-84Article, review/survey (Refereed)
    Abstract [en]

    The present review examines the putative benefits for individuals afflicted with Parkinsonism, whether in the clinical setting or in the animal laboratory, accruing from different exercise regimes. The tendency for patients with Parkinson's disease (PD) to express either normal or reduced exercise capacity appears regulated by factors such as fatigue, quality-of-life and disorder severity. The associations between physical exercise and risk for PD, the effects of exercise on idiopathic Parkinsonism and quality-of-life, the effects of exercise on animal laboratory models of Parkinsonism and dopamine (DA) loss following neurotoxic insults, and the effects of exercise on the DA precursor, L-Dopa, efficacy are examined. It would appear to be case that in view of the particular responsiveness of the dopaminergic neurons to exercise, the principle of 'use it or lose' may be of special applicability among PD patients.

  • 8. Asztely, F.
    et al.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    The diagnosis and treatment of limbic encephalitis2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 6, p. 365-375Article, review/survey (Refereed)
    Abstract [en]

    The term limbic encephalitis (LE) was first introduced in 1968. While this disease was initially considered rare and is often fatal with very few treatment options, several reports published in the last decade provide a better description of this condition as well as possible causes and some cases of successful treatment. The clinical manifestation of LE is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. In addition, EEG often shows focal or generalized slow wave or epileptiform activity, and MRI findings reveal hyperintense signals of the medial temporal lobes in T2-weighted or FLAIR images. The current literature suggests that LE is not a single disorder but is comprised of a group of autoimmune disorders predominantly affecting the limbic system. Before the diagnosis of LE can be determined, other causes of subacute encephalopathy must be excluded, especially those resulting from infectious aetiologies. LE has previously been regarded as a paraneoplastic phenomenon associated with the classical onconeuronal antibodies that are primarily directed against intracellular antigens. However, recent literature suggests that LE is also associated with antibodies that are directed against cell surface antigens, and these cases of LE display a much weaker association to the neoplasm. The treatment options for LE largely depend on the aetiology of the disease and involve the removal of the primary neoplasm. Therefore, a search for the underlying tumour is mandatory. In addition, immunotherapy has been successful in a significant number of patients where LE is not associated with cancer.

  • 9.
    Axelson, Hans W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Öberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    No benefit of treatment with cyclophosphamide and autologous blood stem cell transplantation in multifocal motor neuropathy2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 117, no 6, p. 432-434Article in journal (Refereed)
    Abstract [en]

    Introduction - Patients with multifocal motor neuropathy (MMN) usually respond to intravenous immunoglobulin (IVIG), but because of the short-lasting effect the treatment must be given repeatedly. Remission after treatment with high-dose cyclophosphamide has recently been reported in one patient refractory to IVIG. Case report - Here we report on a patient who responded to IVIG, but temporarily deteriorated dramatically after treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. Today the situation is the same as before the treatment with cyclophosphamide and blood stem cell transplantation, i.e. IVIG is given every 4 weeks. Conclusion - Our patient did not benefit from the treatment with high-dose cyclophosphamide and autologous blood stem cell transplantation. The effect of treatment with high-dose cyclophosphamide in MMN seems to be difficult to predict and that should be paid attention to if this type of treatment is considered.

  • 10.
    Bergman, Eva-Mathilda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, B.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    National registry-based case-control study: comorbidity and stroke in young adults2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 6, p. 394-399Article in journal (Refereed)
    Abstract [en]

    ObjectivesStroke is overrepresented in cohorts of young adults with chronic diseases. The prevalence and impact of comorbidity among young stroke patients have not been compared with individuals without stroke. Our aim was to investigate the association between comorbidity and stroke in young adults. Materials and methodsA nationwide cohort of patients (aged 15-44years), registered in the Swedish Stroke Register, (Riksstroke) 2001-2009, was identified. Age- and sex-matched controls were randomly selected from the Population Register of Sweden. Discharge diagnoses were retrieved from the National Patient Register and grouped by chapter in the International Classification of Diseases 10th revision. Associations between ICD-10 chapters and stroke were stratified (age, sex, and stroke type) and analyzed by multivariable logistic regression. ResultsIn 2599 stroke patients analyzed, the prevalence of vascular risk factors (hypertension 25.3%, dyslipidemia 13.0%, diabetes 9.7%, heart failure 3.2%, and atrial fibrillation 2.8%), all ICD-10 chapters (except pregnancy) and prestroke hospitalizations were more frequent among cases than controls. Independent associations were found between stroke and eight ICD-10 chapters: neoplasms (odds ratios (OR) 1.53, 95% CI 1.15-2.05), blood (OR 1.61, 1.11-2.34), endocrine (OR 2.28, 1.77-2.93), psychiatric (OR 1.50, 1.24-1.81), nervous (OR 1.91, 1.46-2.50), eye (OR 1.67, 1.05-2.64), circulatory (OR 3.05, 2.45-3.80), and symptoms (OR 1.31, 1.13-1.52). The risk of stroke increased by 26% per ICD-10 chapter diagnosed. ConclusionsIn addition to vascular risk factors, comorbidity (represented by ICD-10 chapters) was associated with increased risk of stroke in young individuals. The risk of stroke was further increased with the number of diagnosed ICD-10 chapters.

  • 11.
    Berntsson, Shala G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kristoffersson, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Neurology Policlinic, Department of Medical Specialist, Motala General Hospital, Motala, Sweden.
    Boström, I
    Department of Clinical and Experimental Medicine, Neurology, Medical Faculty, University of Linköping, Linköping, Sweden.
    Feresiadou, Amalia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Department of Clinical and Experimental Medicine, Neurology, Medical Faculty, University of Linköping, Linköping, Sweden; Neurology Policlinic, Department of Medical Specialist, Motala General Hospital, Motala, Sweden.
    Rapidly increasing off-label use of rituximab in multiple sclerosis in Sweden: Outlier or predecessor?2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 327-331Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Off-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis.

    MATERIAL AND METHODS: Review of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6 years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital.

    RESULTS: Presently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%.

    CONCLUSIONS: The share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

  • 12.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Toss, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Agreement between ambulance nurses and physicians in assessing stroke patients2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 129, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    Objectives: If an ambulance nurse could bypass the emergency department (ED) and bring suspected stroke patients directly to a CT scanner, time to thrombolysis could be shortened. This study evaluates the level of agreement between ambulance nurses and emergency physicians in assessing the need for a CT scan, and interventions and monitoring beforehand, in patients with suspected stroke and/or a lowered level of consciousness.

    Materials and Methods: From October 2008 to June 2009 we compared the ambulance nurses’ and ED physicians’ judgement of 200 patients with stroke symptoms . Both groups answered identical questions on patients’ need for a CT scan, and interventions and monitoring beforehand.  

    Results: There was a poor agreement between ambulance nurses and ED physicians in judging the need for a CT scan: κ = 0.22 (95% confidence interval (CI): 0.06–0.37). The nurses’ ability to select the same patients as the physician for a CT scan had a sensitivity of 84% (95% CI: 77–89) and a specificity of 37% (95% CI: 23–53). Agreement concerning the need for interventions and monitoring was also low: κ = 0.32 (95% CI: 0.18–0.47). In 18% of cases, the nurses considered interventions before a CT scan unnecessary when the physicians’ deemed them necessary.

    Conclusions: Additional tools to support ambulance nurses decisions appear to be required before suspected stroke patients can be taken directly to a CT scanner.

     

     

  • 13. Bolin, K
    et al.
    Berggren, F
    Berling, P
    Morberg, S
    Gauffin, H
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Patterns of antiepileptic drug prescription in Sweden: A register-based approach2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 5, p. 521-527Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward.

    MATERIAL AND METHODS: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period.

    RESULTS: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013.

    CONCLUSIONS: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

  • 14. Bolin, K
    et al.
    Berggren, F
    Landtblom, Anne-Marie
    Department of Clinical and Experimental Medicine/Neurology, University of Linköping, UHL, County Council, Linköping, Sweden.
    Prevalence and cost of epilepsy in Sweden -: a register-based approach2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 131, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011.

    METHODS: Cost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications.

    RESULTS: The prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from €2929 to €1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011.

    CONCLUSIONS: The per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalence < 1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

  • 15. Bolin, K
    et al.
    Berggren, F
    Landtblom, Anne-Marie
    Department of Clinical and Experimental Medicine/Neurology, University of Linköping, UHL County Council, Linköping, Sweden.
    Regional variation in prevalence and healthcare utilization due to epilepsy in Sweden2014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, no 6, p. 354-359Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To estimate the regional differences in the prevalence of epilepsy and the associated costs due to inpatient and outpatient care and anti-epileptic drug (AED) utilization for the years 2005 and 2011 in Sweden.

    METHODS: Region-specific estimates of the prevalence of epilepsy were obtained using a method based on a linkage of the healthcare and pharmaceutical registries and the cause of death registry. Regional cost components were estimated using registry data by region on inpatient and outpatient care utilization, AED sales, and mortality. Per-patient utilization and monetary costs were calculated.

    RESULTS: Estimated prevalence of epilepsy varied substantially across the regions in 2011, from 0.76% in Jämtland to 1.08% in Gotland. The national prevalence was 0.88%. The average number of hospitalizations per patient and year decreased at the national level between 2005 and 2011. At the national level, the per-patient specialized care (outpatient) utilization also decreased between 2005 and 2011. However, at the regional level, the decrease was not uniform, and in some counties, the per-patient utilization increased during the period studied. The per-patient utilization of AEDs increased in all counties, except Kronoberg, between 2005 and 2011. Moreover, between-region differences in healthcare and AED utilization, and significant differences between regions and national averages were revealed. Similarly, regional per-patient costs were shown to deviate from the national average in 13 of 21 regions.

    CONCLUSIONS: There is significant variation in the prevalence of epilepsy and the provision of health care for patients with epilepsy across the different regions of Sweden.

  • 16. Bolin, Kristian
    et al.
    Niska, Per-Åke
    Pirhonen, Laura
    Wasling, Pontus
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    The cost-utility of pitolisant as narcolepsy treatment.2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The cost-effectiveness of available pharmacological treatments for narcolepsy is largely unknown. Available pharmacological treatments are associated with tolerability, abuse and adherence issues. Pitolisant is the first inverse agonist of the histamine H3 receptor to be prescribed for the treatment of narcolepsy with and without cataplexy. Studies suggest that pitolisant is both as effective as previously introduced drugs and is associated with fewer adverse effects. The objective in this study was to estimate the cost-effectiveness of pitolisant as monotherapy, and pitolisant as an adjunctive treatment to modafinil, compared to standard treatment.

    MATERIALS & METHODS: Calculations were performed using a Markov model with a 50-year time horizon. Healthcare utilisation and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Probabilistic sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters.

    RESULTS: The cost per additional quality-adjusted life year was estimated at SEK 356 337 (10 SEK ≈1 Euro) for pitolisant monotherapy, and at SEK 491 128 for pitolisant as an adjunctive treatment, as compared to standard treatment. The cost-effectiveness measure was demonstrated to be particularly sensitive to the assumptions made concerning indirect effects on total healthcare utilization and the pitolisant treatment cost.

    CONCLUSIONS: The incremental cost-effectiveness ratios were below the unofficial willingness-to-pay threshold at SEK 500 000. The estimated costs per additional QALY obtained here are likely to overestimate the true cost-effectiveness ratio since significant potential indirect effects - pertaining both to labour-market and household-related productivity - of treatment are not taken into account.

  • 17. Brown, C.
    et al.
    Hasson, H.
    Thyselius, Vanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Almborg, A. -H
    Post-stroke depression and functional independence: a conundrum2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Objectives People who suffer a stroke are at risk of developing post-stroke depression (PSD). Not only does this lower their quality of life but it also increases their risk of another stroke or death. This study aimed to investigate the factors associated with PSD in order to better direct rehabilitation efforts aimed at cutting the incidence of PSD.

    Material and methods This study was based on all patients admitted to the stroke unit of a hospital in southern Sweden from 1 October 2003 to 30 November 2005. The total number of patients involved was 181. Measures were collected at 2 +/- 1 weeks after discharge from hospital, 3 +/- 0.5 months after the occurrence of the stroke and 12 +/- 1 months after the occurrence of the stroke. Information collected was results from the Center of Epidemiologic Studies Depression Scale and the Barthel Index together with demographic data including age, sex, time since stroke and relationship status.

    Results Those patients involved in the study were mainly men (5859%) and generally those either married or cohabiting (5357%). The age of respondents ranged from 32 to 92 years with a mean age of 74.0 (95%CI 72.3775.63) at 2 +/- 1 weeks after discharge. The Barthel Index scores ranged from 15 to 100 with means of between 88.7 and 91.7. Between 15% and 19% of the group were clinically depressed during the time frame of the study. The Barthel Index, measuring functional independence in terms of need for assistance with personal activities of daily living (P-ADL), was consistently associated with PSD.

    Conclusions The differences found in levels of depression between those with lower functional independence after a stroke compared to those more independent in P-ADL, raise the possibility that attention should be paid to therapeutic rehabilitation for stroke patients to help them recover as much functional independence as possible in order to improve their quality of life and lower their chances of developing PSD.

  • 18.
    Burman, Joachim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Bilateral and recurrent optic neuritis in multiple sclerosis2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 3, p. 207-210Article in journal (Refereed)
    Abstract [en]

    Objective - To assess the frequency of bilateral and recurrent optic neuritis (ON) in multiple sclerosis (MS) and to compare these results with epidemiological data of ON in neuromyelitis optica (NMO) and recurrent ON without other signs of disease. Methods - We identified 472 patients with diagnosis of MS from the Swedish Multiple Sclerosis Register. These patients were evaluated for the presence of ON and whether the ON was the presenting symptom of MS; unilateral or bilateral; monophasic or recurrent. Results - Twenty-one percent presented with ON as their first manifestation of MS. The proportion of patients developing a second attack of ON before demonstration of other manifestations of MS was 5.5% and the frequency of recurrent bilateral ON as the presenting symptom was 3.8%. Only two patients presented with simultaneously appearing bilateral ON corresponding to 0.42%. Conclusion - Recurrent ON, whether unilateral or bilateral, is a common presentation of MS. As MS is a much more common disease than NMO, care must be taken when evaluating the work-up of patients with recurrent ON. In some cases repeated MRI and lumbar punctures are warranted to improve diagnostic accuracy, even in the presence of the serological marker NMO-IgG.

  • 19.
    Burman, Joachim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Zetterberg, H
    Sahlgrenska Academy, University of Gothenburg.
    Fransson, Moa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Loskog, Angelica SI.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Assessing tissue damage in multiple sclerosis: a biomarker approach2014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, no 2, p. 81-89Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Magnetic resonance imaging (MRI) of the brain and spinal cord is the gold standard for assessing disease activity in multiple sclerosis (MS). MRI is an excellent instrument for determination of accumulated damage to the brain and spinal cord, but tells us little about ongoing tissue damage. In this study, biomarkers of oligodendrocyte, axonal and astrocyte injury were related to MRI and clinical findings and used to assess tissue damage in MS.

    MATERIALS AND METHODS:

    Cerebrospinal fluid from 44 patients with relapsing-remitting MS, 20 with secondary progressive MS and 15 controls were investigated with ELISA to determine levels of myelin basic protein (MBP), neurofilament light (NFL) and glial fibrillary acidic protein (GFAp). Patients underwent MRI of the brain and spinal cord, and gadolinium enhancing lesions, T1 lesions and T2 lesions were counted.

    RESULTS:

    Patients in clinical relapse and patients with nonsymptomatic gadolinium enhancing lesions had high levels of MBP and NFL, indicating ongoing damage to oligodendrocytes and axons. The level of MBP dropped quickly within a week from the onset of a relapse, whereas NFL remained elevated for several weeks and GFAp slowly rose during the course of a relapse. Relapsing-remitting MS patients without gadolinium enhancing lesions had values of MBP, NFL and GFAp similar to controls, while patients with secondary progressive disease had moderately increased values of all biomarkers.

    CONCLUSIONS:

    Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.

  • 20.
    Bådagård, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Braun, Madelene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Nilsson, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Stridh, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Negative predictors of shunt surgery outcome in normal pressure hydrocephalusIn: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404Article in journal (Refereed)
    Abstract [en]

    Objectives

    The prevalence of idiopathic normal pressure hydrocephalus (iNPH) and vascular comorbidity increases with age. It has not been clarified if high age and vascular disease are negative predictors of shunt surgery outcome in patients with iNPH. The aim of this study was to investigate the impact of high age and vascular comorbidity on outcome after shunt surgery in patients with iNPH.

    Methods

    All 332 patients with iNPH who were treated with shunts between 2011 and 2015 at a single centre were consecutively included. Hellström iNPH scale, without the neuropsychological tests, was calculated preoperatively and at follow‐up 12 months after shunt surgery. Outcome was defined as the difference between the post‐operative and preoperative iNPH scale scores. A multivariable model was used to investigate the predictive effects of age and vascular comorbidity on shunt surgery outcome.

    Results

    In a multivariable analysis of covariance (ANCOVA) with post‐operative outcome as the dependent variable, increasing age (years, B = −0.63, P < .001) and history of ischaemic stroke (B = −10.06, P = .0038) were negative predictors of shunt surgery outcome after controlling for waiting time for surgery, symptom severity at preoperative control, presence of diabetes mellitus, hypertension, hyperlipidaemia, history of myocardial infarction, duration of symptoms and shunt complications.

    Conclusions

    High age and established cerebrovascular disease are associated with less favourable outcome after shunt surgery in patients with iNPH.

  • 21.
    Corell, Alba
    et al.
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Carstam, L
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Henriksson, R
    Regional Cancer Centre Stockholm, Gotland, Sweden; Department of Radiation Science and Oncology, University hospital, Umeå, Sweden.
    Jakola, A S
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden; Department of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway.
    Age and surgical outcome of low-grade glioma in Sweden2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 359-368Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low-grade gliomas (LGG) are slow-growing primary brain tumors that typically affect young adults. Advanced age is widely recognized as a poor prognostic factor in LGG. The impact of age on postoperative outcome in this patient group has not been systemically studied.

    METHODS: We performed a nationwide register-based study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with a supratentorial LGG (WHO grade II astrocytoma, oligoastrocytoma, or oligodendroglioma) during 2005-2015. Patient- and tumor-related characteristics, postoperative complications, and survival were compared between three different age groups (18-39 years, 40-59 years, and ≥60 years).

    RESULTS: We identified 548 patients; 204 patients (37.2%) aged 18-39 years, 227 patients (41.4%) aged 40-59 years, and 117 patients (21.4%) ≥60 years of age. Unfavorable preoperative prognostic factors (eg, functional status and neurological deficit) were more common with increased age (P < .001). In addition, overall survival was significantly impaired in those 60 years and above (P < .001). We observed a clear dose-response for age with separation of survival curves at 50 years. Biopsy was more common in patients ≥60 years (P < .001). Subgroup analysis of patients with resection revealed a higher amount of postoperative neurological deficits in older patients (P = .029).

    CONCLUSION: In general, older patients with LGG have several unfavorable prognostic factors compared with younger patients but seem to tolerate surgery in a comparable fashion. However, more neurological deficits were observed following resections in elderly. Our data further support a cutoff at 50 years rather than 40 years for selection of high-risk patients.

  • 22.
    Ekegren, Titti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Grundström, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lindholm, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Upregulation of Bax protein and increased DNA degradation in ALS spinal cord motor neurons1999In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 100, no 5, p. 317-321Article in journal (Refereed)
    Abstract [en]

    Objectives

    To investigate if degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is related to altered levels of the apoptosis regulating proteins Bcl-2 and Bax. In addition, immunoreactivity of the cysteine protease ICH-1L and detection of motor neurons with DNA fragmentation, indicative of apoptosis, was also studied.

    Material and methods

    The immunoreactivity of Bcl-2, Bax and ICH-1L were compared in ALS and control spinal cord motor neurons by immunohistochemical analysis and motor neurons with DNA fragmentation were identified by the TUNEL-method.

    Results

    The results demonstrate an increased expression of Bax in the ALS material as compared to controls but no change in Bcl-2 and ICH-1L expressions. Moreover, a larger proportion of motor neurons stained positive for TUNEL in ALS spinal cords.

    Conclusion

    Present study suggest an upregulation of the cell death promoting protein Bax and increased DNA degradation, indicative of apoptosis, in spinal motor neurons of ALS patients.

  • 23.
    Fagius, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Normal outcome of pregnancy with ongoing treatment with natalizumab2014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 129, no 6, p. e27-e29Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment of multiple sclerosis (MS) with natalizumab during pregnancy is not recommended due to potential risks for the foetus. Despite strong advice accidental pregnancies occur.

    CASE: A 32-year old woman with MS since the age of 26 was treated with natalizumab since January 2008. Treatment was stopped April 2011 due to pregnancy plans, but was restarted following an MS relapse. The patient was thoroughly informed about potential foetal risks, but nevertheless she one year later disclosed that she was pregnant in gestational week 15. Treatment was continued, since the first trimester had passed. The pregnancy course was normal and a healthy daughter was born at full gestational term.

    CONCLUSIONS: This is the second known case where natalizumab treatment continued throughout the whole gestational period.

  • 24.
    Finnsson, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melberg, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 2, p. 135-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5th to 6th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F-fluorodeoxyglucose positron emission tomography (PET).

    METHODS: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

    RESULTS: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

    CONCLUSIONS: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.

  • 25.
    Halawa, Imad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Vlachogiannis, Pavlos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Amandusson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Elf, Kristin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Zetterberg, H.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 137, no 2, p. 199-203Article in journal (Refereed)
    Abstract [en]

    Objectives

    Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI.

    Methods

    We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T-tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome.

    Results

    Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055-1.680. P=.016].

    Conclusion

    Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI.

  • 26. Hoglund, A.
    et al.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Palhagen, S.
    Fredrikson, S.
    Hagell, P.
    Is excessive daytime sleepiness a separate manifestation in Parkinson's disease?2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, no 2, p. 97-104Article in journal (Refereed)
    Abstract [en]

    BackgroundExcessive daytime sleepiness (EDS) is common in Parkinson's disease (PD), but its role and relation to other PD features is less well understood. ObjectiveTo investigate potential predictors of EDS in PD and to explore how EDS relates to other motor and non-motor PD features. Methods118 consecutive persons with PD (54% men; mean age, 64) were assessed regarding EDS using the Epworth Sleepiness Scale (ESS) and a range of motor and non-motor symptoms. Variables significantly associated with ESS scores in bivariate analyses were used in multiple regression analyses with ESS scores as the dependent variable. Principal component analysis (PCA) was conducted to explore the interrelationships between ESS scores and other motor and non-motor PD aspects. ResultsAmong 114 persons with complete ESS data, significant independent associations were found between ESS scores and axial/postural/gait impairment, depressive symptoms, and pain (R-2, 0.199). ESS scores did not load significantly together with any other PD features in the PCA. ConclusionsOnly a limited proportion of the variation in EDS could be accounted for by other symptoms, and EDS did not cluster together with any other PD features in PCAs. This suggests that EDS is a separate manifestation differing from, for example, poor sleep quality and fatigue.

  • 27.
    Isacson, D
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bingefors, K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kristiansen, I S
    Nyholm, D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 379-86Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. METHODS: Of 18 patients completing a 6-week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire-39 (PDQ-39). RESULTS: During the trial and follow-up, major diurnal fluctuations were observed, especially for hyperkinesia, 'off' time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, 'off' time and ability to walk, with improved outcomes with PDQ-39. CONCLUSIONS: Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient's QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.

  • 28.
    Jacobsson, Lars
    et al.
    Lund Univ, Dept Hlth Sci, Rehabil Med Res Grp, Lund, Sweden;Sunderby Hosp, Dept Rehabil Med, Lulea, Sweden;Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden.
    Lexell, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Lexell: Rehabilitation Medicine. Lund Univ, Dept Hlth Sci, Rehabil Med Res Grp, Lund, Sweden;Sunderby Hosp, Dept Rehabil Med, Lulea, Sweden.
    Functioning and disability from 10 to 16 years after traumatic brain injury2020In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 141, no 2, p. 115-122Article in journal (Refereed)
    Abstract [en]

    Objectives

    With increased long-term survival after traumatic brain injury (TBI), there is a need to understand the life situation many years after the injury. In this study, we have assessed persons on average 16 years after their injury and determined changes over 6 years in overall outcome, living condition, marital status and vocational situation, and in their functioning and disability.

    Materials & Methods

    Individuals (n = 49, mean age 45 years, 28-70 years) who were assessed 6-15 years (average 10 years) post-TBI were reassessed 12-21 years after their injury (average 16 years) using internationally established TBI outcome measures.

    Results

    From the first to the second assessment, overall outcome using the Glasgow Outcome Scale (GOS) was stable for a large majority and no significant changes in marital status or vocational situation were found. There was some significant, but very small, decline regarding cognitive function, home integration and social integration. In the multiple regression analysis, there was a small significant decline in the Mayo-Portland Adaptability Inventory (MPAI-4) Adjustment subscale score for women with a moderate-to-severe injury.

    Conclusions

    The very small changes over 6 years imply that persons with a TBI can reach and maintain a stable level of functioning many years post-TBI. Women with a moderate-to-severe TBI seem to be more vulnerable and may experience a small decline in some aspects of their functioning related to anxiety, depression, irritability, pain and headache and fatigue. The relatively small sample requires further studies to confirm these findings.

  • 29.
    Jakobsson Larsson, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ozanne, A G
    Neurology, Clinical Neuroscience, Sahlgrenska Universitetssjukhus, Göteborg, Sweden.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    A prospective study of quality of life in amyotrophic lateral sclerosis patients2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 6, p. 631-638Article in journal (Refereed)
    Abstract [en]

    OBJECTS: The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time.

    MATERIALS AND METHODS: Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up.

    RESULTS: Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life.

    CONCLUSION: The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life.

  • 30. Kleberg, Johan L.
    et al.
    Lindberg, C.
    Winblad, S.
    Facial memory deficits in myotonic dystrophy type 12014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, no 5, p. 312-318Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo evaluate facial memory ability (FMA) in patients with myotonic dystrophy type 1 (DM1). We also explored the relationship between FMA and neuropsychological data, disease-related factors, and CTG repeat expansion size. Materials and methodsPatients with DM1 (n=33) and healthy subjects (n=30) were tested with the faces task of the Rivermead Behavioural Memory Test - Extended version (RBMT-E) and an additional set of neuropsychological tests. Clinical data were collected, and CTG repeat size was quantified in blood lymphocytes. ResultsLow results on the faces task were more common in patients with DM1 compared with healthy subjects (P<0.05), with 36% of the patients showing a poor/impaired performance. DM1 patients with deficits in FMA performed significantly worse on tests measuring visual-construction ability and memory. Furthermore, these patients more often falsely recognised unknown faces as known. Deficits in FMA were not associated with any disease-related factor, including CTG repeat expansion size. ConclusionsThese findings revealed deficits in FMA in the DM1 group, which was associated with reduced construction- and visual memory ability.

  • 31.
    Kleberg, Johan Lundin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Facial memory deficits in myotonic dystrophy type 12014In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 130, no 5, p. 312-318Article in journal (Refereed)
  • 32.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ericsson, A.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia2003In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, no 5, p. 339-45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. RESULTS: The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. CONCLUSION: Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.

  • 33.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ericsson, A.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Akterin, S.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Src family kinase-inhibitor PP2 reduces focal ischemic brain injury2004In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, no 3, p. 175-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the neuroprotective potential of the Src family kinase (SFK) inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo(3,4-d)pyrimidine (PP2) in transient focal cerebral ischemia in the rat. MATERIAL AND METHODS: Sprague-Dawley rats were exposed to transient (90 min) middle cerebral artery occlusion (MCAO) and evaluated after 1 day of survival. PP2 (1.5 mg/kg i.p.) or vehicle was given 30 min after MCAO. The lesions were examined with magnetic resonance imaging (MRI), tri-phenyl tetrazolium chloride (TTC) staining and the functional outcome was determined using neurological scoring according to Bederson et al. RESULTS: PP2-treated rats showed approximately 50% reduction of infarct size on T2-weighted MRI and in TTC staining compared with controls (P < 0.05). Moreover, the neurological score was better in the PP2 group than controls (P < 0.05). CONCLUSION: PP2 is a potential neuroprotective agent in cerebral ischemia-reperfusion. The interference of PP2 with SFKs and/or other pathways remains to be elucidated.

  • 34.
    Lennmyr, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Karlsson, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gerwins, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ata, K. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Terent, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Activation of mitogen-activated protein kinases in experimental cerebral ischemia2002In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 106, no 6, p. 333-40Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Mitogen-activated protein kinases (MAPK) regulate cell survival and differentiation. The aim of the present study is to investigate the activation pattern of different MAPKs [extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase (JNK) and p38] after cerebral ischemia. MATERIAL AND METHODS: Rats were subjected to cerebral ischemia using a model for transient (2 h) and permanent middle cerebral artery occlusion (MCAO). The rats were allowed 6 h to 1 week of survival before immunohistochemical evaluation with phospho-specific antibodies, recognizing activated MAPKs. RESULTS: ERK was activated in ipsilateral blood vessels, neurons and glia, but also in contralateral vessels. JNK activation was absent in neurons but appeared in arterial blood vessels and glia at the lesion side. Active p38 was observed in macrophages in maturing infarcts. CONCLUSIONS: ERK and JNK may participate in the angiogenic response to cerebral ischemia. ERK, but not JNK, was activated in neurons, possibly indicating a pathophysiologic role. Active p38 might be involved in the inflammatory reaction.

  • 35. 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.

  • 36.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    White matter disorders with autosomal dominant heredity2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 1, p. 71-72Article in journal (Refereed)
  • 37.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Åkerlund, P.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Silander, H.C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Wibom, R.
    Khaled, A.
    Nennesmo, I.
    Lundberg, P. O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Olsson, Y.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Monozygotic twins with MELAS-like syndrome lacking ragged red fibers and lactacidaemia1996In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 94, no 4, p. 233-41Article in journal (Refereed)
    Abstract [en]

    Typical cases of MELAS present a combination of clinical and neuroradiological features, lactacidaemia, and ragged red fibers (RRFs) in striated muscle. We have observed a MELAS-like syndrome in monozygotic twins. They developed seizures typically in conjunction with physical exertion, sleep deprivation or febrile episodes. Stroke-like episodes occurred usually during seizures. In twin 2 the course was fatal at age 20 years. Neuroradiological findings were typical of MELAS. Plasma lactate was normal in both. CSF lactate was normal in twin 1 and normal/elevated in twin 2. RRFs were not seen in muscle biopsies of the twins. Complex I activity was reduced in muscle in twin 1. Brain tissue removed at epilepsy surgery in twin 2 showed the presence of mitochondrial angiopathy. The commonest mitochondrial DNA mutation in MELAS, at base pair 3243, was absent. Lactacidaemia and mitochondrial myopathy with RRFs constitute part of the diagnostic criteria of MELAS. However, the absence of these features does not exclude mitochondrial disorder with the serious manifestations of MELAS (seizures and stroke-like episodes) as seen in these twins.

  • 38.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Örlén, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Entesarian, Miriam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Dahlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gustavson, Karl Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Re-evaluation of the dysequilibrium syndrome2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 1, p. 28-33Article in journal (Refereed)
    Abstract [en]

    Objectives - To re-evaluate middle-aged Swedish patients diagnosed with dysequilibrium syndrome (DES) in childhood and to compare their clinical and neuroimaging features to DES with VLDLR gene mutations (DES-VLDR). Materials and methods - Six patients from five families underwent neurological examination and magnetic resonance imaging (MRI) of the brain. Blood samples from the patients were screened for serum carbohydrate-deficient transferrin (s-CDT; disialotransferrin). The very-low-density lipoprotein receptor (VLDLR) gene was sequenced. Results - Five patients had non-progressive cerebellar ataxia (NPCA), dysarthria and short stature. Mental retardation and strabismus, characteristic for DES-VLDLR, were inconsistent among our patients. None of our patients had VLDLR mutations or MRI findings characteristic of DES-VLDLR. MRI findings were variable from a normal cerebellum to marked cerebellar hypoplasia or atrophy and signal intensity changes. One patient was diagnosed with congenital disorder of glycosylation type 1a (CDG-1a). Conclusions - DES was originally coined on mainly clinical grounds before MRI and specific genetic tests were available, both of which should be used to arrive at an appropriate diagnosis.

  • 39.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Constantinescu, R
    Holmberg, B
    Dizdar, N
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, no 5, p. 345-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

  • 40.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ehrnebo, M
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Trolin, C G
    Bäckström, T
    Panagiotidis, G
    Spira, J
    Nyström, C
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 124-132Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).

    MATERIALS AND METHODS:

    A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.

    RESULTS:

    Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.

    CONCLUSIONS:

    Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.

  • 41.
    Popova, Svetlana N
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Tarvainen, I
    Capellari, S
    Parchi, P
    Hannikainen, P
    Pirinen, E
    Haapasalo, H
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Divergent clinical and neuropathological phenotype in a Gerstmann-Sträussler-Scheinker P102L family2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 5, p. 315-323Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Gerstmann-Sträussler-Scheinker syndrome belongs to the genetic prion diseases being associated with mutations in the prion protein gene (PRNP). The most common is the point mutation at codon 102, leading to the substitution of proline to leucine (P102L). Previous reports have indicated a phenotypic heterogeneity among individuals with this mutation. Here, we describe the clinical and pathological phenotype in members of the first Finnish kindred with the P102L mutation in the PNRP gene.

    MATERIALS AND METHODS:

    Genetic and clinical information was available in five members of a family, while a systematic histologic and immunohistochemical assessment of the post-mortem brain was carried out in three.

    RESULTS:

    Clinical presentation, disease duration and the clinical phenotype (ataxia vs dementia) varied between patients. There was a significant correlation between clinical symptoms and the neuroanatomical distribution of prion protein-immunoreactive aggregates, i.e. subtentorial predominance in ataxia vs cortical predominance in dementia. A significant concomitant Alzheimer is disease-related pathology was observed in the brain of one patient with dementia as onset symptom.

    CONCLUSIONS:

    This is the first Scandinavian family carrying the P102L mutation in the PRNP gene. Gerstmann-Sträussler-Scheinker syndrome should be considered in the differential diagnosis when handling with patients with ataxia and/or dementia of unclear aetiology.

  • 42. Poutiainen, E.
    et al.
    Elovaara, I.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Vilkki, J.
    Lähdevirta, J.
    Iivanainen, M.
    Cognitive decline in patients with symptomtic HIV-1 infection: No decline in asymptomatic infection1996In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 93, no 6, p. 421-7Article in journal (Refereed)
    Abstract [en]

    Thirty-six HIV-1-infected predominantly well-functioning subjects were followed up for one year by repeated neuropsychological, clinical neurological, neuroradiological, and immunological examinations. Changes in cognitive performance related to the severity of HIV-1 infection as well as to neuroradiological or immunological changes were studied. A decline in cognitive speed and flexibility was found in symptomatic subjects (ARC, AIDS). The impairment was especially pronounced in patients with progression of brain atrophy. These findings suggest a brain pathology underlying the cognitive decline in ambulatory outpatients with symptomatic HIV-1 infection. A practice effect was found in asymptomatic subjects (ASX, LAS) and in those with unchanged CT/MRI scans. No systematic relationship was found between cognitive change and immunological change.

  • 43. Pålhagen, S E
    et al.
    Dizdar, N
    Hauge, T
    Holmberg, B
    Jansson, R
    Linder, J
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sydow, O
    Wainwright, M
    Widner, H
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 6, p. e29-e33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care.

    METHODS: Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, ≥3 months after surgery, and then every 3 months.

    RESULTS: Twenty-seven treatment-naïve subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean ± SD), baseline = 52.1 ± 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 ± 16.7, N = 27, P = 0.003; month 12 = 42.5 ± 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean ± SD), baseline = 33.6 ± 10.8, N = 27, month 0 = 27.1 ± 11.8, N = 27, P = 0.001; 12 months = 28.8 ± 12.8, n = 23, P = 0.126.

    CONCLUSIONS: LCIG provides functional improvement beginning at first visit that is sustained for 12 months.

  • 44.
    Rostedt Punga, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stålberg, Erik V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, no 3, p. 207-211Article in journal (Refereed)
    Abstract [en]

    Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins.

     

  • 45.
    Sahlstrom, T.
    et al.
    Lund Univ, Dept Clin Sci, Neurol, Fac Med, Lund, Sweden.
    Eklund, M.
    Lund Univ, Dept Hlth Sci Mental Hlth Act & Participat MAP, Lund, Sweden.
    Timpka, J.
    Lund Univ, Dept Clin Sci, Neurol, Fac Med, Lund, Sweden;Skane Univ Hosp, Dept Neurol, Lund, Sweden.
    Henriksen, T.
    Univ Hosp Bispebjerg, Movement Disorder Clin, Copenhagen, Denmark.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Odin, P.
    Lund Univ, Dept Clin Sci, Neurol, Fac Med, Lund, Sweden;Skane Univ Hosp, Dept Neurol, Lund, Sweden;Cent Hosp, Dept Neurol, Bremerhaven, Germany.
    Workforce participation and activities in Parkinson's disease patients receiving device-aided therapy2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 1, p. 78-84Article in journal (Refereed)
    Abstract [en]

    Objectives: Many countries have an aging population, and it is thus likely that Parkinson's disease (PD) will become an increasing health problem. It is important to ensure this group can use their resources in the best way possible, including remaining in the work market. This study aimed to investigate workforce participation and daily activities among patients with PD receiving device-aided therapy to provide new knowledge that may be used to inform decisions about these therapy options.

    Materials and Methods:This was a retrospective, descriptive quantitative pilot study, including 67 patients with PD from 3 centers in Sweden and Denmark. Included patients were younger than 67years at the time of introduction of device-aided therapy. Eligible patients were identified by the Swedish national Parkinson patient registry or by the treating neurologist. Quantitative interviews were made by telephone.

    Results:A majority of the patients could perform the same, or more, amount of activities approximately 5years after the introduction of device-aided therapy. A small number of patients receiving deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG) were able to increase their work capacity within 1year of initiating device-aided therapy and a remarkably high share could still work at the end-point of this study, approximately 15years since the diagnosis of PD.

    Conclusions:Device-aided therapy may sustain or increase daily activities and workforce participation in patients with PD who have not yet reached retirement age. There is need for prospective studies, both quantitative and qualitative, to confirm these results.

  • 46.
    Senek, Marina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hellström, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Albo, Jaan
    Vällingby läkarhus, Vällingby, Sweden.
    Svenningsson, Per
    Karolinska institutet, Stockholm, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    First clinical experience with levodopa/carbidopa microtablets in Parkinson’s disease2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 6, p. 727-731Article in journal (Refereed)
    Abstract [en]

    Background: Levodopa is the most effective symptomatic treatment throughout thecourse of Parkinson’s disease, but as the disease progresses, there may be a need forindividualized, fine-tunedtreatments.

    Aim: To evaluate individualized levodopa/carbidopa dosing using microtablets dispensedwith a dose dispenser, with respect to efficacy and usability as perceived bypatients.

    Methods: Patient records and dose dispenser reports from patients previously or currentlytreated with microtablets and a dose dispenser were reviewed, and a patientquestionnaire concerning effect and usability was sent to patients.

    Results: Eleven patient records, four dose dispenser reports and nine survey responseswere obtained. The treatment effect was considered to be improved by six of ninepatients. One-thirdfound their bradykinesia to be improved, and the non-troublesomedyskinesia was unchanged according to a majority of patients; however, some experiencedthe duration and magnitude of troublesome dyskinesia to be worse. The usabilitywas generally rated as good. The four dose dispenser reports obtained showed97(±5)% total adherence.

    Conclusions: The experienced effect of treatment can, for some patients, be improvedby the use of microtablets, and the dose dispenser was considered user-friendly.Further studies with a larger study population and prospective design are needed toconfirm the results.

  • 47. Sikk, K
    et al.
    Taba, P
    Haldre, S
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Thurfjell, L
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eriksson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Färnstrand, C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure2010In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 121, no 4, p. 237-243Article in journal (Refereed)
    Abstract [en]

    Objective - To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). Methods - Neurophysiological examinations, magnetic resonance imaging (MRI), single-photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. Results - Peripheral nervous system was not affected. No patients had reduced uptake of (123)I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. Conclusions - Presynaptic neurons in the nigrostriatal pathway are intact in Mn-induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse.

  • 48. Sikk, Katrin
    et al.
    Taba, Pille
    Haldre, Sulev
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Zjablov, G.
    Asser, T.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Irreversible motor impairment in young addicts - ephedrone, manganism or both?2007In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 115, no 6, p. 385-389Article in journal (Refereed)
    Abstract [en]

    Background -  Parkinsonian syndrome related to intravenous use of a `designer' psychostimulant, derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in Estonia. Objective -  To describe the symptomatology of four young patients, history of drug administration and chemical analysis of a drug batch. Methods -  Mental and motor function and quality of life were scored and ephedrone was analyzed using electrospray mass spectrometry. Manganese content of the final synthetic mixture was analyzed using Inductively Coupled Plasma-Atomic Emission Spectrometry. Results -  None of the four cases scored below the dementia threshold in MMSE, while other ratings (UPDRS, H&Y, PDQ-39) corresponded to disabilities seen in relatively advanced Parkinson's disease. The ephedrone yield of the reaction was approximately 44% and the mixture was found to contain 0.6 g/l of manganese. Conclusions -  The cases were exposed to extreme manganese load. Their symptomatology is probably identical to manganism. The role of ephedrone is presently unknown. Physicians must be aware of early signs of manganism in patients within social risk groups.

  • 49.
    Thomas, Ilias
    et al.
    Dalarna Univ, Dept Microdata Anal, Falun, Sweden.
    Memedi, Mevludin
    Örebro Univ, Sch Business, Örebro, Sweden.
    Westin, Jerker
    Dalarna Univ, Dept Microdata Anal, Falun, Sweden.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    The effect of continuous levodopa treatment during the afternoon hours2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, p. 70-75Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this retrospective study was to investigate whether patients with Parkinson's disease, who are treated with levodopa‐carbidopa intestinal gel (LCIG), clinically worsen during the afternoon hours and if so, to evaluate whether this occurs in all LCIG‐treated patients or in a subgroup of patients.

    Methods: Three published studies were identified and included in the analysis. All studies provided individual response data assessed on the treatment response scale (TRS), and patients were treated with continuous LCIG. Ninety‐eight patients from the three studies fulfilled the criteria. t tests were performed to find differences on the TRS values between the morning and the afternoon hours, linear mixed effect models were fitted on the afternoon hours' evaluations to find trends of wearing‐off, and patients were classified into three TRS categories (meaningful increase in TRS, meaningful decrease in TRS, non‐meaningful increase or decrease).

    Results: In all three studies, significant statistical differences were found between the morning TRS values and the afternoon TRS values (P‐value <=0.001 in all studies). The linear mixed effect models had significant negative coefficients for time in two studies, and 48 out of 98 patients (49%) showed a meaningful decrease in TRS during the afternoon hours.

    Conclusion: The results from all studies were consistent, both in the proportion of patients in the three groups and in the value of TRS decrease in the afternoon hours. Based on these findings, there seems to be a group of patients with predictable "off" behavior in the later parts of the day.

  • 50.
    Tolf, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Carlson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Granberg, Tobias
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden; Karolinska Univ Hosp, Dept Radiol, Div Neuroradiol, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 140, no 5, p. 320-327Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS).

    Material and methods: Case series of patients with relapsing‐remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as “no evidence of disease activity‐4,” sustained for a period of at least 5 years without any ongoing disease‐modifying treatment. Furthermore, MS was considered as “resolved” if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well.

    Results: Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved.

    Conclusions: Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible.

     

12 1 - 50 of 61
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