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  • 1. Al-Chalabi, Ammar
    et al.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Chandran, Siddharthan
    Chio, Adriano
    Corcia, Philippe
    Couratier, Philippe
    Danielsson, Olof
    de Carvalho, Mamede
    Desnuelle, Claude
    Grehl, Torsten
    Grosskreutz, Julian
    Holmøy, Trygve
    Ingre, Caroline
    Karlsborg, Merete
    Kleveland, Grethe
    Christoph Koch, Jan
    Koritnik, Blaz
    KuzmaKozakiewicz, Magdalena
    Laaksovirta, Hannu
    Ludolph, Albert
    McDermott, Christopher
    Meyer, Thomas
    Ropero, Bernardo Mitre
    Pardina, Jesus Mora
    Nygren, Ingela
    Petri, Susanne
    Povedano Panades, Mónica
    Salachas, Francois
    Shaw, Pamela
    Silani, Vincenzo
    Staaf, Gert
    Svenstrup, Kirsten
    Talbot, Kevin
    Tysnes, Ole-Bjørn
    Van Damme, Philip
    van der Kooi, Anneke
    Weber, Markus
    Weydt, Patrick
    Wolf, Joachim
    Hardiman, Orla
    van den Berg, Leonard H.
    July 2017 ENCALS statement on edaravone2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 7-8, s. 471-474Artikel i tidskrift (Övrigt vetenskapligt)
    Ladda ner fulltext (pdf)
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  • 2.
    Andersen, Peter M.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Kuźma-Kozakiewicz, Magdalena
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland; Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland.
    Keller, Jürgen
    Department of Neurology, University of Ulm, Ulm, Germany.
    Maksymowicz-Śliwińska, Anna
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Barć, Krzysztof
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Nieporęcki, Krzysztof
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Finsel, Julia
    Department of Neurology, University of Ulm, Ulm, Germany.
    Vazquez, Cynthia
    Department of Neurology, University of Ulm, Ulm, Germany.
    Helczyk, Olga
    Department of Neurology, University of Ulm, Ulm, Germany.
    Linse, Katharina
    Department of Neurology, Technische Universität Dresden, and German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
    Häggström, Ann-Cristin E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Stenberg, Erica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Semb, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Ciećwierska, Katarzyna
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Szejko, Natalia
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Uttner, Ingo
    Department of Neurology, University of Ulm, Ulm, Germany.
    Herrmann, Andreas
    Department of Neurology, Technische Universität Dresden, and German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
    Petri, Susanne
    Department of Neurology, Hannover Medical School, Hannover, Germany.
    Meyer, Thomas
    Department of Neurology, Charité CVK, Berlin, Germany.
    Ludolph, Albert C.
    Department of Neurology, University of Ulm, Ulm, Germany; German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.
    Lulé, Dorothée
    Department of Neurology, University of Ulm, Ulm, Germany.
    Caregivers’ divergent perspectives on patients’ well-being and attitudes towards hastened death in Germany, Poland and Sweden2022Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 23, nr 3-4, s. 252-262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient’s well-being and preferences is a prerequisite for patient-centered surrogate decision making.

    Methods: In Germany (N = 84), Poland (N = 77) and Sweden (N = 73) patient-caregiver dyads were interviewed. Standardized questionnaires on well-being (ADI-12 for depressiveness; ACSA for global quality of life) and wish for hastened death (SAHD) were used in ALS patients. Additionally, caregivers were asked to fill out the same questionnaires by anticipating patients’ perspective (surrogate perspective).

    Results: Caregivers significantly underestimated patients’ well-being in Germany and Poland. For Swedish caregivers, there were just as many who underestimated and overestimated well-being. The same was true for wish for hastened death in all three countries. For Swedish and Polish patients, caregivers’ estimation of well-being was not even associated with patients’ responses and the same was true for estimation of wish for hastened death in all three countries. Older caregivers and those with the most frequent encounter with the patient were the closest in their rating of well-being and wish for hastened death to the patients’ actual state, while caregivers with chronic disease him/herself were more likely to underestimate patient’s well-being.

    Discussion: Despite distinct cultural differences, there was a clear discrepancy between patients’ and caregivers’ perspective on patients’ well-being and preferences towards life in all three countries. This possible bias in caregivers’ judgment needs to be taken into account in surrogate decision making.

  • 3. Benatar, Michael
    et al.
    Wuu, Joanne
    Lombardi, Vittoria
    Jeromin, Andreas
    Bowser, Robert
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malaspina, Andrea
    Neurofilaments in pre-symptomatic ALS and the impact of genotype2019Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 20, nr 7-8, s. 538-548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6-12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.

  • 4. Czell, David
    et al.
    Sapp, Peter C.
    Neuwirth, Christoph
    Weber, Markus
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brown, Robert H.
    Further analysis of KIFAP3 gene in ALS patients from Switzerland and Sweden2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 3-4, s. 302-304Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of studies suggests that susceptibility to ALS may be influenced by variants in multiple genes. While analyses of the 10% of cases of familial origin have identified more than 33 monogenic ALS-causing genetic defects, little is known about genetic factors that influence susceptibility or phenotype in sporadic ALS (SALS). We and others conducted a genome-wide association study (GWAS) in a cohort of 1014 ALS cases from Western Europe, England and the United States, and identified an intronic single nucleotide polymorphism (SNP) rs1541160 in the KIFAP3 gene that was statistically associated with improved survival. We have now completed an additional survival analysis examining the impact of the rs1541160 genotype in a cohort of 264 ALS and progressive bulbar palsy (PBP) cases. In the combined cohort of 264 patients, the CC, CT and TT genotypes for rs1541160 were detected, respectively, in 8.3% (22), 41.7% (110) and 50.0% (132). This study does not show an influence of KIFAP3 variants on survival in the studied Swiss and Swedish cohort. There was a difference in survival between the US and English patients and the patients from the Netherlands. The effect of KIFAP3 variants may be population specific, or the rs1541160 association reported previously may have been a false-positive.

  • 5. De Carvalho, Mamede
    et al.
    Ryczkowski, Adam
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gromicho, Marta
    Grosskreutz, Julian
    Kuzma-Kozakiewicz, Magdalena
    Petri, Susanne
    Piotrkiewicz, Maria
    Miltenberger Miltenyi, Gabriel
    International Survey of ALS Experts about Critical Questions for Assessing Patients with ALS2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 7-8, s. 505-510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To define an applicable dataset for ALS patient registries we weighted specific clinical items as scored by worldwide ALS experts.

    Methods: Sixty participants were invited based on relevant clinical work, publications and personal acquaintance. They rated 160 clinical items consensually agreed by the members of our project, incorporating specialists from five European Centres. Scoring scheme was defined as: 1 - essential; 2 - important; 3 - not very important. A mixed effect model was applied to rank items and to find possible correlations with geographical region (Europe vs. outside Europe).

    Results: We received 40 responses, 20 from Europe and 20 from outside; 42/160 data were scored as essential by >50% of the respondents, including: date of birth, gender, date of disease onset, date of diagnosis, ethnicity, region of onset, predominant upper neuron (UMN) or lower motor neuron (LMN) impairment, proximal versus distal weakness, respiratory symptoms, dysarthria, weight loss, signs of LMN/UMN involvement, emotional incontinence, cognitive changes, respiratory signs, neck weakness, body mass index, ALSFRS-R at entry, ALSFRS-R subscores at entry, timing and pattern of spreading and staging, electromyography, spirometry, MRI, CK level, riluzole intake, genetic background, history of physical exercise and previous and current main occupation. Four components were scored as non-relevant, including place of birth, blood pressure and pain at onset. There was no significant difference between regions (European vs. non-European countries).

    Conclusions: Our study identified a consensual set of clinical data with 42 specific items that can be used as a minimal data set for patient registers and for clinical trials.

  • 6.
    Dilliott, Allison A.
    et al.
    Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
    Al Nasser, Ahmad
    Schulich School of Medicine and Dentistry, Western University, London, Canada.
    Elnagheeb, Marwa
    Department of Genetics, University of North Carolina, NC, Chapel Hill, United States.
    Fifita, Jennifer
    Centre for MND Research, Macquarie Medical School, Macquarie University, Sydney, Australia.
    Henden, Lyndal
    Centre for MND Research, Macquarie Medical School, Macquarie University, Sydney, Australia.
    Keseler, Ingrid M.
    Department of Biomedical Data Science, Stanford University, CA, Stanford, United States.
    Lenz, Steven
    PreventionGenetics, WI, Marshfield, United States.
    Marriott, Heather
    Department of Basic and Clinical Neuroscience, King’s College London, London, United Kingdom.
    Mccann, Emily
    Centre for MND Research, Macquarie Medical School, Macquarie University, Sydney, Australia.
    Mesaros, Maysen
    Medical University of South Carolina, SC, Charleston, United States.
    Opie-Martin, Sarah
    Department of Basic and Clinical Neuroscience, King’s College London, London, United Kingdom.
    Owens, Emma
    Department of Genetics, University of North Carolina, NC, Chapel Hill, United States.
    Palus, Brooke
    Department of Genetics, University of North Carolina, NC, Chapel Hill, United States.
    Ross, Justyne
    Department of Genetics, University of North Carolina, NC, Chapel Hill, United States.
    Wang, Zhanjun
    Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
    White, Hannah
    Invitae, CA, San Francisco, United States.
    Al-Chalabi, Ammar
    Department of Basic and Clinical Neuroscience, King’s College London, London, United Kingdom.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Benatar, Michael
    Department of Neurology, University of Miami, FL, Miami, United States.
    Blair, Ian
    Centre for MND Research, Macquarie Medical School, Macquarie University, Sydney, Australia.
    Cooper-Knock, Johnathan
    Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom.
    Harrington, Elizabeth A.
    Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, NY, New York City, United States.
    Heckmann, Jeannine
    Division of Neurology, University of Cape Town, Cape Town, South Africa.
    Landers, John
    Department of Neurology, University of Massachusetts Amherst, MA, Amherst, United States.
    Moreno, Cristiane
    Department of Neurology, University of Sao Paulo, Sao Paulo, Brazil.
    Nel, Melissa
    Division of Neurology, University of Cape Town, Cape Town, South Africa.
    Rampersaud, Evadnie
    Center for Applied Bioinformatics, St. Jude’s Children’s Hospital, TN, Memphis, United States.
    Roggenbuck, Jennifer
    Department of Internal Medicine, Ohio State University, OH, Columbus, United States.
    Rouleau, Guy
    Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; Department of Genetics, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
    Traynor, Bryan
    Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, MD, Bethesda, United States.
    Van Blitterswijk, Marka
    Department of Neuroscience, Mayo Clinic, FL, Jacksonville, United States.
    Van Rheenen, Wouter
    Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht, Netherlands.
    Veldink, Jan
    Department of Neurology, University Medical Center Utrecht Brain Center, Utrecht, Netherlands.
    Weishaupt, Jochen
    Department of Neurology, Heidelberg University, Heidelberg, Germany.
    Drury, Luke
    PreventionGenetics, WI, Marshfield, United States.
    Harms, Matthew B.
    Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, NY, New York City, United States.
    Farhan, Sali M. K.
    Department of Genetics, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
    Clinical testing panels for ALS: global distribution, consistency, and challenges2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 5-6, s. 420-435Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.

    Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests.

    Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes.

    Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.

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  • 7.
    Finsel, Julia
    et al.
    Department of Neurology, Ulm University, Ulm, Germany.
    Winroth, Ivar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ciećwierska, Katarzyna
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland.
    Helczyk, Olga
    Department of Neurology, Ulm University, Ulm, Germany.
    Stenberg, Erica A.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Häggström, Ann-Cristin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ludolph, Albert C.
    Department of Neurology, Ulm University, Ulm, Germany.
    Uttner, Ingo
    Department of Neurology, Ulm University, Ulm, Germany.
    Semb, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Pilczuk, Beata
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland.
    Szejko, Natalia
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland; Department of Bioethics, Medical University of Warsaw, Warsaw, Poland.
    Rosentul, Simona
    Lulé, Dorothée
    Department of Neurology, Ulm University, Ulm, Germany.
    Kuźma-Kozakiewicz, Magdalena
    Department of Neurology, University Clinical Centre of Medical University of Warsaw, Warsaw, Poland; Department of Neurology, Medical University of Warsaw, Warsaw, Poland; Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Determining impairment in the Swedish, Polish and German ECAS: the importance of adjusting for age and education2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 5-6, s. 475-484Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Age and years of education are strong predictors of cognitive performance in several versions of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and cutoffs for the Swedish and Polish versions are not established yet. Here we evaluated the performance of healthy subjects on the national versions of the Swedish and Polish ECAS and compared cognitive performance on three European translations of the ECAS.

    Methods: The ECAS performances of healthy subjects from Sweden (n = 111), Poland (n = 124) and Germany (n = 86) were compared. Based on the test results on the national versions of ECAS, age- and education-adjusted cutoffs were compared for the German, Swedish and Polish versions, respectively.

    Results: Age and years of education correlated with performance in the ECAS. Swedish subjects under the age of 60 years and Swedish subjects with low education level scored significantly higher in memory than the respective German and Polish subgroups. German and Polish subjects over 60 years of age performed significantly better in language than the respective Swedish subgroup. The Polish cohort in total had lower executive scores compared to the Swedish cohort, and lower than the German subjects in the higher education subgroup.

    Conclusions: The results highlight the importance of establishing age- and education-adjusted ECAS cutoffs not only in general, but also for seemingly similar populations of different origins. The results should be taken into account when comparing cognition data across patient populations including in drug trials where an ECAS test result is being used as an inclusion criterium or outcome measure.

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  • 8.
    Foucher, Juliette
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Winroth, Ivar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Lovik, Anikó
    Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Methodology and Statistics Unit, Institute of Psychology, Leiden University, Leiden, Netherlands.
    Sennfält, Stefan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Pereira, Joana B.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lule, Dorothee
    Neuropsychology, Department of Neurology, Ulm University, Ulm, Germany.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ingre, Caroline
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Validity and reliability measures of the Swedish Karolinska version of the Edinburgh Cognitive and Behavioral ALS Screen (SK-ECAS)2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 7-8, s. 713-718Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A.

    Methods: The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated.

    Results: We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach’s alpha of 0.79.

    Conclusions: This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients.

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  • 9. Gromicho, Marta
    et al.
    Kuzma-Kozakiewicz, Magdalena
    Szacka, Katarzyna
    Nieporecki, Krzysztof
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Grosskreutz, Julian
    Petri, Susanne
    Pinto, Susana
    Uysal, Hilmi
    Swash, Michael
    De Carvalho, Mamede
    Motor neuron disease beginning with frontotemporal dementia: clinical features and progression2021Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 22, nr 7-8, s. 508-516Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset.

    Methods: 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinical data, functional decline and survival.

    Results: Twenty six patients (3.1%) had FTD-onset of whom seven (26.9%) had coincident motor dysfunction. In those with isolated FTD-onset, motor symptoms developed after a median of 12 months (IQR: 4-18). FTD-onset patients were older at presentation; the bulbar-region was more frequently first affected than in the motor-onset group; there was a predominant upper motor neuron (UMN) phenotype; fasciculations were less common than in motor onset disease but facial and upper limb apraxia was more frequent; as well as ALS and FTD familial history. No differences were observed for gender, frequency of C9orf72 hexanucleotide repeat expansion, family history of Alzheimer's and Parkinson's diseases, median delay from motor symptoms to diagnosis, median ALSFRS-R rate of change, handedness, emotional lability, depression, weight loss, resting tremor, bradykinesia, sensory changes or neuropathy. Clinical and demographic features were similar between FTD-onset patients developing bulbar MND and bulbar-onset ALS patients. Once bulbar symptoms manifested functional progression and survival were similar to those of bulbar-onset ALS patients.

    Conclusions: MND patients with FTD-onset have a distinctive phenotype characterized by predominant UMN presentation and rapid progression to bulbar involvement. The main factor impacting functional decline and survival is the onset of bulbar dysfunction.

  • 10.
    Ingre, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Pinto, Susana
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Press, Rayomand
    Danielsson, Olof
    de Carvalho, Mamede
    Guðmundsson, Grétar
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    No association between VAPB mutations and familial or sporadic ALS in Sweden, Portugal and Iceland2013Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 14, nr 7-8, s. 620-627Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Linkage analysis in Brazilian families with amyotrophic lateral sclerosis (ALS) revealed that a missense mutation p.Pro56Ser in a conserved gene VAMP-associated protein type B and C (VAPB) co-segregates with disease.

    Methods: Blood samples were studied from 973 Swedish, 126 Portuguese and 19 Icelandic ALS patients, and from 644 control subjects. 


    Results: We identified five VAPB mutations, two of which are novel, in 14 Swedish ALS patients and in nine control individuals from Sweden and Portugal. The 14 patients with VAPB mutations all carried a diagnosis of sporadic ALS. Mutations were also found in healthy adult relatives. The p.Asp130Glu VAPB mutation was also found in two patients from an Icelandic ALS family, but the mutation did not co-segregate with disease. All patients were instead found to be heterozygous for a p.Gly93Ser SOD1 mutation. There were no clinical differences between them, suggesting that the p.Asp130Glu VAPB mutation is unrelated to the disease process. 


    Conclusions: The VAPB mutations were as frequent in control individuals as in patients. This observation, in combination with the finding of several healthy relatives carrying the VAPB mutations and no ancestors with ALS disease, suggests that it is unlikely that these VAPB mutations are pathogenic

  • 11.
    Ingre, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Press, Rayomand
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    A 50bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden2016Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 17, nr 5-6, s. 452-457Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.

  • 12.
    Keskin, Isil
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Berdynski, Mariusz
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Polish Academy of Sciences, Warsaw, Poland.
    Hjertkvist, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Rofougaran, Reza
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nilsson, Torbjörn K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Glass, Jonathan D.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 5-6, s. 457-463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.Methods: Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay.Results: Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72(HRE). In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios.Conclusion: Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.

  • 13.
    Kliest, Tessa
    et al.
    Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands.
    Van Eijk, Ruben P.A.
    Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands; Biostatistics & Research Support, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands.
    Al-Chalabi, Ammar
    Department of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, United Kingdom; Department of Neurology, King’s College Hospital, London, United Kingdom.
    Albanese, Alberto
    IRCCS Humanitas Research Hospital Rozzano, Milan, Italy.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Amador, Maria Del Mar
    Département de Neurologie, Centre de référence SLA, France; Hôpital de la Pitié Salpêtrière, AP-HP, Paris, France.
    Bråthen, Geir
    Department of Neurology, University Hospital of Trondheim, Trondheim, Norway; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
    Brunaud-Danel, Veronique
    ALS centre, CHU, University of Lille Nord de France, Lille, France.
    Brylev, Lev
    Bujanov Moscow City Clinical Hospital, Moscow, Russian Federation; Moscow Research and Clinical Center for Neuropsychiatry of the Healthcare Department, Moscow, Russian Federation.
    Camu, William
    ALS Centre CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
    De Carvalho, Mamede
    Institute of Physiology-Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Department of Neurosciences and Mental Health, H Santa Maria-CHLN, Lisbon, Portugal.
    Cereda, Cristina
    Regional Newborn Screening Laboratory, Vittore Buzzi Children's Hospital-University of Milan, Italy.
    Cetin, Hakan
    Department of Neurology, Medical University of Vienna, Vienna, Austria.
    Chaverri, Delia
    Neurology Service, Hospital Universitario La Paz, Madrid, Spain.
    Chiò, Adriano
    'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy; Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
    Corcia, Philippe
    Centre Constitutif SLA, CHRU de Tours - Fédération des centres SLA Tours-Limoges, LitORALS, Tours, France.
    Couratier, Philippe
    Centre Constitutif de reference SLA-Fédération Tours-Limoges, CHU de Limoges, Limoges, France.
    De Marchi, Fabiola
    "Maggiore della Carità" University Hospital, Novara, Italy.
    Desnuelle, Claude
    Hôpital Pasteur 2–CHU de Nice, Nice, France.
    Van Es, Michael A.
    Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands.
    Esteban, JesÚs
    ALS Research Lab - ALS Unit, Instituto de Investigación Sanitaria Hospital 12 de Octubre "i + 12", CIBERER, Madrid, Spain.
    Filosto, Massimiliano
    Department of Clinical and Experimental Sciences, University of Brescia; NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy.
    GarcÍa Redondo, Alberto
    ALS Research Lab - ALS Unit, Instituto de Investigación Sanitaria Hospital 12 de Octubre "i + 12", CIBERER, Madrid, Spain.
    Grosskreutz, Julian
    Precision Neurology, Dept. of Neurology, Lübeck University Hospital, Lübeck, Germany.
    Hanemann, Clemens O.
    University of Plymouth, Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.
    Holmøy, Trygve
    Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Høyer, Helle
    Department of Medical Genetics, Telemark Hospital, Skien, Norway.
    Ingre, Caroline
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Koritnik, Blaz
    Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
    Kuzma-Kozakiewicz, Magdalena
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Lambert, Thomas
    Department of Neurology, Royal Stoke University Hospital, Stoke, United Kingdom.
    Leigh, Peter N.
    Department of Neuroscience, Brighton and Sussex Medical School, Trafford Centre for Biomedical Research, University of Sussex, Brighton, United Kingdom.
    Lunetta, Christian
    NEMO Clinical Center, Serena Onlus Foundation, Milan, Italy; NEMO LAB, Milan, Italy.
    Mandrioli, Jessica
    Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy; Department of Neuroscience, St. Agostino Estense Hospital, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
    Mcdermott, Christopher J.
    Department of Neuroscience, University of Sheffield, Sheffield Institute for Translational Neuroscience, Sheffield, United Kingdom.
    Meyer, Thomas
    ALS Outpatient Department, Charité–Universitatsmedizin Berlin, Berlin, Germany.
    Mora, Jesus S.
    ALS Unit/Neurology, Hospital San Rafael, Madrid, Spain.
    Petri, Susanne
    Department of Neurology, Hannover Medical School, Hannover, Germany.
    Povedano, Mónica
    Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.
    Reviers, Evy
    European Organization for Professionals and Patients with ALS (EUpALS) & ALS Liga Belgium, Leuven, Belgium.
    Riva, Nilo
    Department of Neurology, Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
    Roes, Kit C.B.
    Department of Health Evidence, Section Biostatistics, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands.
    Rubio, Miguel Á.
    Neuromuscular Unit, Department of Neurology, Hospital del Mar, Barcelona, Spain; Instituto Hospital del Mar de Investivaciones Médicas (IMIM), Barcelona, Spain.
    Salachas, François
    Département de Neurologie, Centre de référence SLA, France; Hôpital de la Pitié Salpêtrière, AP-HP, Paris, France.
    Sarafov, Stayko
    Clinic of General Neurology, Medical University Sofia, University Hospital Alexandrovska, Sofia, Bulgaria.
    Sorarù, Gianni
    Department of Neurosciences, University of Padova, Padova, Italy.
    Stevic, Zorica
    Clinic of Neurology, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
    Svenstrup, Kirsten
    Department of Neurology, Bispebjerg-Frederiksberg Hospital and Rigshospitalet, University Hospital of Copenhagen, Denmark.
    Møller, Anette Torvin
    Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
    Turner, Martin R.
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Van Damme, Philip
    Department of Neurosciences, Laboratory for Neurobiology, KU Leuven and Centre for Brain & Disease Research, VIB, Leuven Brain Institute, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
    Van Leeuwen, Lucie A.G.
    Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands.
    Varona, Luis
    Department of Neurology, Basurto University Hospital, Vizcaya, Spain.
    VÁzquez Costa, Juan F.
    ALS Unit and Neuromuscular Disease Unit, Department of Neurology, Hospital La Fe, Valencia, Spain.
    Weber, Markus
    Neuromoscular Disease Unit/ALS Clinic, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
    Hardiman, Orla
    Academic Unit of Neurology Trinity College Dublin Ireland, Dublin, Ireland.
    Van Den Berg, Leonard H.
    Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht, Netherlands.
    Clinical trials in pediatric ALS: a TRICALS feasibility study2022Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 23, nr 7-8, s. 481-488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).

    Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.

    Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.

    Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.

    Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.

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  • 14. Kuzma-Kozakiewicz, Magdalena
    et al.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Elahi, Elahe
    Alavi, Afagh
    Sapp, Peter C.
    Morita, Mitsuya
    Zekanowski, Cezary
    Berdynski, Mariusz
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
    Putative founder effect in the Polish, Iranian and United States populations for the L144SSOD1mutation associated with slowly uniform phenotype of amyotrophic lateral sclerosis2021Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 22, nr 1-2, s. 80-85Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations inSOD1cause approximately 12-25% of familial ALS and approximate to 2% of apparently sporadic ALS cases. Clinical phenotypes linked to SOD1 mutations are heterogeneous and intra-familial variability of the clinical phenotype is frequently observed. SOD1 L144S mutation, identified also in Brazil, Iran and United States, is the second most frequent mutation among ALS patients in Poland. So far, 10 FALS pedigrees with SOD1 L144S mutation have been reported worldwide. The aim of the study was to establish the origin of SOD1 L144S mutation in geographically distinct populations. The clinical presentation of the Polish patients was compared with those from the previously reported populations (26 ever-reported patients). Clinically, L144S mutation is associated with both sporadic and familial ALS of relatively slow uniform course, a prevalent onset in the lower limbs, either classic or PMA presentation and a long survival time. Like in the case of other previously described SOD1 mutations, there was an intra-familial heterogeneity and reduced penetrance for ALS was observed. We propose that the L144S SOD1 mutation in the three studied populations has a common founder most likely of Polish origin.

  • 15. Longinetti, Elisa
    et al.
    Regodón Wallin, Amanda
    Samuelsson, Kristin
    Press, Rayomand
    Zachau, Anne
    Ronnevi, Lars-Olof
    Kierkegaard, Marie
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hillert, Jan
    Fang, Fang
    Ingre, Caroline
    The Swedish motor neuron disease quality registry2018Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 19, nr 7-8, s. 528-537Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We set up the Swedish Motor Neuron Disease (MND) Quality Registry to assure early diagnosis and high-quality health care for all MND patients (mainly amyotrophic lateral sclerosis, ALS), and to create a research base by prospectively following the entire MND population in Sweden. Methods: Since 2015, the MND Quality Registry continuously collects information about a wide range of clinical measures, biological samples, and quality of life outcomes from all MND patients recruited at the time of MND diagnosis in Sweden and followed at each clinic visit approximately every 12 weeks. The Registry includes an Internet based patient own reporting portal that involves patients in the registration of their current symptoms and health status. Results: As of 20th January 2017, the MND Quality Registry included 99% of the MND patients of the Stockholm area (N = 194), consisting mostly of ALS patients (N = 153, 78.9%), followed by patients labeled as MND due to a neurophysiology finding but not fulfilling the criteria for ALS (N = 20, 10.3%), primary lateral sclerosis (N = 13, 6.7%), and progressive spinal muscular atrophy patients (N = 8, 4.1%). A higher proportion of these patients were women (N = 100, 52%), and women and men had a similar age at symptoms onset (59 years). Conclusions: Main strengths of the MND Quality Registry are its clinical, quantitative, qualitative, and prospective nature, providing the researchers potential means of identifying appropriate candidates for clinical trials and other research projects, as well as assuring to the patients an effective and adequate time spent on-site with the healthcare professionals.

  • 16.
    Malmström, Nina
    et al.
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jakobsson Larsson, Birgitta
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden.
    Nilsson, Stefan
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for Person-Centred Care, University of Gothenburg, Gothenburg, Sweden.
    Öhlén, Joakim
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for Person-Centred Care, University of Gothenburg, Gothenburg, Sweden; Palliative Centre at the Sahlgrenska University Hospital Region Västra Götaland, Gothenburg, Sweden.
    Nygren, Ingela
    Department of Neurology, Uppsala University Hospital, Uppsala, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Ozanne, Anneli
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Living with a parent with ALS - adolescents' need for professional support from the adolescents' and the parents' perspectives2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 7-8, s. 727-735Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The aim of the study was to qualitatively investigate the adolescents’ need for professional support when a parent has amyotrophic lateral sclerosis (ALS)–from the adolescents’ and the parents’ perspectives.

    Methods: A total of 37 individual semi-structured single interviews with 18 families were conducted, including 11 adolescents aged 8-25 and 26 parents, 13 with ALS and 13 co-parents. Data was analysed using qualitative content analysis.

    Results: Both adolescents and parents described the adolescents as needing professional support but found it difficult to articulate this need. However, the results indicate that the adolescents needed help in bringing manageability into their lives due to the uncertainty of living with the illness in the family. It was therefore essential to ensure that the adolescents were not forgotten in the disease context and that their needs for being involved as well as for obtaining information and understanding, was addressed. The importance of offering the adolescents support early was emphasized, but also of actively helping the families to master challenges in their everyday life. Support adapted to each family’s unique situation and preferences was desired, as the adolescents’ need for support seemed to be individual, disease-dependent and varied during different phases.

    Conclusion: Given the adolescents’ need for information and understanding, healthcare professionals must actively work to reach the adolescents as early as possible. It is crucial to ensure that the adolescents are given the opportunity to be involved based on their own conditions, as well as to support the families to strengthen their communication.

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  • 17.
    Nordin, Angelica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Akimoto, Chizuru
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Alstermark, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Baumann, Peter
    Pinto, Susana
    de Carvalho, Mamede
    Hübers, Annemarie
    Nordin, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ludolph, Albert C.
    Weishaupt, Jochen H.
    Meyer, Thomas
    Grehl, Torsten
    Schweikert, Kathi
    Weber, Markus
    Burkhardt, Christian
    Neuwirth, Christoph
    Holmøy, Trygve
    Morita, Mitsuya
    Tysnes, Ole-Bjørn
    Benatar, Michael
    Wuu, Joanne
    Lange, Dale J.
    Bisgård, Carsten
    Asgari, Nasrin
    Tarvainen, Ilkka
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Ulm University, Ulm, Germany.
    Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation: a large multinational screening study2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 3-4, s. 256-264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele. In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.

  • 18. Oeckl, Patrick
    et al.
    Jardel, Claude
    Salachas, Francois
    Lamari, Foudil
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bowser, Robert
    de Carvalho, Mamede
    Costa, Julia
    van Damme, Philip
    Gray, Elizabeth
    Grosskreutz, Julian
    Hernandez-Barral, Maria
    Herukka, Sanna-Kaisa
    Huss, Andre
    Jeromin, Andreas
    Kirby, Janine
    Kuzma-Kozakiewicz, Magdalena
    Amador, Maria del Mar
    Mora, Jesus S.
    Morelli, Claudia
    Muckova, Petra
    Petri, Susanne
    Poesen, Koen
    Rhode, Heidrun
    Rikardsson, Anna-Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Robberecht, Wim
    Rodriguez Mahillo, Ana I.
    Shaw, Pamela
    Silani, Vincenzo
    Steinacker, Petra
    Turner, Martin R.
    Tuzun, Erdem
    Yetimler, Berrak
    Ludolph, Albert C.
    Otto, Markus
    Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS2016Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 17, nr 5-6, s. 404-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a reverse round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n=150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p<0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 +/- 19.1%. We calculated a diagnostic cut-off of >568.5pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.

  • 19.
    Pinto, Susana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Instituto de Medicina Molecular and Institute of Physiology, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
    de Carvalho, Mamede
    Comparison of slow and forced vital capacities on ability to predict survival in ALS2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 7-8, s. 528-533Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Slow (SVC) and forced (FVC) vital capacities are the most used pulmonary function tests in amyotrophic lateral sclerosis (ALS). It is unknown if they equally predict survival in ALS. The aim of the present study was to compare both measures in predicting survival in this disease.

    Methods: Consecutive definite/probable ALS patients (2000-2014) in whom respiratory tests were performed at baseline and four months later were included. All patients were evaluated with the revised ALS functional rating scale (ALSFRS-R), respiratory (RofALSFRS-R), bulbar (ALSFRSb), upper and lower limb subscores, SVC, FVC, maximal inspiratory (MIP) and expiratory (MEP) pressures. King's functional staging system was applied retrospectively. Survival analysis was carried out by univariate Kaplan-Meier log-rank test. Multivariate Cox proportional hazards model determined significant independent variables.

    Results: We included 469 patients (270 males; mean onset age 61.0 +/- 11.5 years; mean disease duration from first symptoms to first visit: 15.8 +/- 16.1months; 329 spinal and 140 bulbar onset). FVC and SVC were strongly correlated (r(2)=0.981, p<0.001). Significant survival prognostic variables (Kaplan-Meier analyses) were onset region, age, disease duration, ALSFRS-R, ALSFRSb, RofALSFRS-R, ALSFRS-R decay, SVC, FVC, MIP, MEP and King's staging (p0.01). Final Cox model including the significant variables showed similar results for FVC and SVC (p<0.001). Moreover, 1% decrease in either predicted values increased death probability by 1.02.

    Conclusion: FVC and SVC are inter-changeable in predicting survival in ALS.

  • 20. Van Der Spek, Rick A.
    et al.
    Van Rheenen, Wouter
    Pulit, Sara L.
    Kenna, Kevin P.
    Ticozzi, Nicola
    Kooyman, Maarten
    Mclaughlin, Russell L.
    Moisse, Matthieu
    Van Eijk, Kristel R.
    Van Vugt, Joke J. F. A.
    Iacoangeli, Alfredo
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Basak, A. Nazli
    Blair, Ian
    De Carvalho, Mamede
    Chio, Adriano
    Corcia, Philippe
    Couratier, Phillipe
    Drory, Vivian E.
    Glass, Jonathan D.
    Hardiman, Orla
    Mora, Jesus S.
    Morrison, Karen E.
    Mitne-Neto, Miguel
    Robberecht, Wim
    Shaw, Pamela J.
    Panades, Monica P.
    Van Damme, Philip
    Silani, Vincenzo
    Gotkine, Marc
    Weber, Markus
    Van Es, Michael A.
    Landers, John E.
    Al-Chalabi, Ammar
    Van Den Berg, Leonard H.
    Veldink, Jan H.
    Reconsidering the causality of TIA1 mutations in ALS2018Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 19, nr 1-2, s. 1-3Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    Yilmaz, Rüstem
    et al.
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Grehl, Torsten
    Department of Neurology, Centre for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus Rüttenscheid, Essen, Germany.
    Eckrich, Lukas
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Marschalkowski, Ines
    Department of Neurology, Centre for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus Rüttenscheid, Essen, Germany.
    Weishaupt, Kanchi
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Valkadinov, Ivan
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Simic, Melita
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Brenner, David
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany; Department of Neurology, University Ulm, Ulm, Germany.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Wolf, Joachim
    Department of Neurology, Diakonissen Hospital Mannheim, Mannheim, Germany.
    Weishaupt, Jochen H.
    Division of Neurodegenerative Disorders, Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences, Heidelberg University, Mannheim, Germany.
    Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers2023Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 24, nr 5-6, s. 414-419Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: ALS patients with a negative family history (sporadic ALS, SALS) represent more than 90% of all ALS cases. In light of the gene-specific therapies that are currently in development for ALS, knowledge about the genetic landscape of SALS in Germany is urgently needed.

    Objectives: We aimed to determine the frequency of C9orf72 hexanucleotide repeat expansion (HRE) and SOD1 mutations among patients in Germany with a diagnosis of sporadic or idiopathic ALS.

    Methods: We genotyped SALS patients from three German ALS centers. Sanger sequencing, fragment length analysis, and repeat-primed PCR technologies were used to detect mutations in SOD1 and C9orf72 HRE. Pathological C9orf72 HRE results were confirmed in an independent laboratory.

    Results: In 302 patients with SALS, 27 (8.9%) patients with a C9orf72 HRE mutation were detected. Moreover, we identified two patients with a pathogenic SOD1 mutation, one patient with a heterozygous p.D91A mutation in SOD1, and three additional patients with rare SOD1 variants not predicted to change the amino acid sequence.

    Conclusions: According to our data, the proportion of SALS patients with SOD1 mutations is in the expected range, whereas that with C9orf72 HRE is higher, suggesting a reduced penetrance. A considerable number of SALS patients can be amenable to gene-specific therapies.

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