Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)—Data From a Local Norwegian Cohort

Objective: We aimed to determine the effectiveness of natalizumab (NTZ) by assessing overall No Evidence of Disease Activity 3 (NEDA-3) in a local Norwegian cohort. Background: NTZ is an immunomodulating drug used in the treatment of multiple sclerosis (MS). It has typically been used as a second-line treatment, but certain patients with high disease activity have started directly with NTZ. Methods: This retrospective cohort study includes all patients who received NTZ for relapsing–remitting MS at Nordland Hospital in the period 2008–2018. In June 2019, status for every patient was assessed, and a survival curve was used to show the cumulative probability of achieving NEDA-3 over time. Results: The cohort consisted of 66 patients, 49 women and 17 men with a mean age of 40.0 ± 10.8 years. Each patient received on average 45.8 ± 36.4 NTZ infusions. Mean age and Expanded Disability Status Scale (EDSS) at first infusion was 34.8 ± 10.5 and 3.2 ± 1.9, respectively. Prior to NTZ treatment, 83% had used other disease modulating drugs and 65% were anti-JC virus (JCV) seronegative. During the study period, seven patients converted to seropositive. In 2019, 40 patients had switched or stopped treatment: 19 due to positive JCV serostatus, 9 due to disease activity, 7 due to adverse effects or complications (1 progressive multifocal leukoencephalopathy), 2 due to pregnancy, and 3 due to autologous hematopoietic cell transplantation abroad. Three patients experienced rebound in the wake of discontinuation (7.5%). Of the patients receiving NTZ for more than 3 years (n = 33), 50% had achieved NEDA-3 after 3 years. Compared to those with evidence of disease activity (EDA), these NEDA-3 patients had significant lower EDSS score before first NTZ treatment (p = 0.04). They were also slightly, but not significantly, younger at debut of their MS, at the diagnosis and at first NTZ treatment. Of all the patients who ever started on NTZ, 23% had achieved NEDA-3 5 years later. The mean EDSS in 2019 was 3.6 ± 2.5. Conclusion: Despite the high rate of treatment switch, mainly due to the risk of PML, almost one in four who started on NTZ achieved NEDA-3 after 5 years, and the overall disease progression was low in the total cohort. Treating less advanced disease seems to predict better long-term stability

Effect of innovative vs. usual care physical therapy in subacute rehabilitation after stroke. A multicenter randomized controlled trial

Background: Research on stroke rehabilitation often addresses common difficulties such as gait, balance or physical activity separately, a fragmentation contrasting the complexity in clinical practice. Interventions aiming for recovery are needed. The purpose of this study was to investigate effects of a comprehensive low-cost physical therapy intervention, ICoreDIST, vs. usual care on postural control, balance, physical activity, gait and health related quality of life during the first 12 weeks post-stroke. Methods: This prospective, assessor-masked randomized controlled trial included 60 participants from two stroke units in Norway. Participants, who were randomized to I-CoreDIST (n = 29) or usual care physical therapy (n = 31), received 5 sessions/week when in-patients or 3 sessions/week as out-patients. Primary outcomes were the Trunk Impairment Scale-modified Norwegian version (TISmodNV) and activity monitoring (ActiGraphsWgt3X-BT). Secondary outcomes were the Postural Assessment Scale for Stroke, MiniBesTEST, 10- meter walk test, 2-minute walk test, force-platform measurements and EQ5D3L. Stroke specific quality of life scale was administered at 12 weeks. Linear regression and non-parametric tests were used for statistical analysis. Results: Five participants were excluded and seven lost to follow-up, leaving 48 participants in the intention-to-treat analysis. There were no significant between-group effects for primary outcomes: TIS-modNV (p = 0,857); daily average minutes of sedative (p = 0.662), light (p = 0.544) or moderate activity (p = 0.239) and steps (p = 0.288), or secondary outcomes at 12 weeks except for significant improvements on EQ5D-3L in the usual care group. Withingroup changes were significant for all outcomes in both groups except for activity levels that were low, EQ5D-3L favoring the usual care group, and forceplatform data favoring the intervention group. Conclusions: Physical therapy treatment with I-CoreDIST improved postural control, balance, physical activity and gait during the first 12 weeks after a stroke but is not superior to usual care

Embodiment, tailoring, and trust are important for co-construction of meaning in physiotherapy after stroke: A qualitative study.

Background and Purpose: Physiotherapy, with an emphasis on high intensity, individually tailored, and person-centered treatment, is an effective route for recovery after a stroke. No single approach, however, has been deemed paramount, and there is limited knowledge about the patient experience of assessment, goal-setting, and treatment in physiotherapy. In this study, we seek to report patient experiences of I-CoreDIST-a new physiotherapy intervention that targets recovery-and those of usual care. The purpose is to investigate how individuals with stroke experience the bodily and interactive course of physiotherapy during their recovery process. Methods: A qualitative study, nested within a randomized controlled trial, consisting of in-depth interviews with 19 stroke survivors who received either I-CoreDIST or usual care. Data were analyzed using systematic text condensation, and this analysis was informed by enactive theory. Results: Interaction with the physiotherapist, which was guided by perceived bodily changes, fluctuated between being, on the one hand, formal/explicit and, on the other, tacit/implicit. The experiences of participants in the intervention group and the usual care group differed predominantly with regards to the content of therapy sessions and the means of measuring progress; divergences in levels of satisfaction with the treatment were less pronounced. The perception of positive bodily changes, as well as the tailoring of difficulty and intensity, were common and essential features in generating meaning and motivation. An embodied approach seemed to facilitate sense-making in therapy situations. In the interaction between the participants and their physiotherapists, trust and engagement were important but also multifaceted, involving both interpersonal skills and professional expertise. Conclusion: The embodied nature of physiotherapy practice is a source for sense-making and meaning-construction for patients after a stroke. Trust in the physiotherapist, along with emotional support, is considered essential. Experiencing progress and individualizing approaches are decisive motivators.The study was funded by the Northern Norway Regional Health Authority

Comorbidity in multiple sclerosis patients from Nordland County, Norway - validated data from the Norwegian Patient Registry

Postponed access: the file will be available after 2021-12-21Background: Knowledge of comorbid disorders is important to optimize therapy for multiple sclerosis (MS), but data are limited. The aim of this study was to assess comorbidity in persons with MS living in Nordland County on January 1, 2017. Methods: Data were retrieved from the Norwegian Patient Registry (2008-2017) and validated through review of electronic hospital charts (1970-2017). Comorbidity was defined as any distinct disorder, classified in the International Classification of Diseases (ICD-10), that had existed or occurred after the diagnosis of MS was established. Results: Data from 637 subjects were reviewed, and 97.5% were registered with at least one comorbid condition. Malignant melanoma was found in 0.5%, and non-melanoma skin cancers in 1.9%. In female subjects, breast cancer was found in 3.3%. Hypothyroidism was confirmed in 3.1%, type-1 diabetes in 0.3%, type-2 diabetes in 3.9%, psychosis in 0.6%, epilepsy in 2.8%, myocardial infarction in 1.7%, subarachnoid hemorrhage in 0.2%, cerebral infarction in 0.6%, pulmonary embolism in 0.9%, inflammatory bowel disease in 1.3%, and rheumatoid arthritis in 0.6%. Conclusion: Compared to reports from other Norwegian epidemiological studies, a higher proportion of inflammatory bowel disease and epilepsy was found. This is in accordance with findings from other studies. The prevalence of non-melanoma skin cancers was significantly higher than in the general Norwegian population as they were reported by The Cancer Registry of Norway.acceptedVersio

The precarity of patient participation - a qualitative interview study of experiences from the acute stroke and rehabilitation journey

Introduction: Active patient participation is an important factor in optimizing post-stroke recovery, yet it is often low, regardless of stroke severity. The reasons behind this trend are unclear. Purpose: To explore how people who have suffered a stroke, perceive the transition from independence to dependence and whether their role in post-stroke rehabilitation influences active participation Methods: In-depth interviews with 17 people who have had a stroke. Data were analyzed using systematic text condensation informed by the concept of autonomy from enactive theory. Results: Two categories emerged. The first captures how the stroke and the resultant hospital admission produces a shift from being an autonomous subject to “an object on an assembly line.” Protocol-based investigations, inactivity, and a lack of patient involvement predominantly determine the hospital context. The second category illuminates how people who have survived a stroke passively adapt to the hospital system, a behavior that stands in contrast to the participatory enablement facilitated by community. Patients feel more prepared for the transition home after inpatient rehabilitation rather than following direct discharge from hospital. Conclusion: Bodily changes, the traditional patient role, and the hospital context collectively exacerbate a reduction of individual autonomy. Thus, an interactive partnership between people who survived a stroke and multidisciplinary professionals may strengthen autonomy and promote participation after a stroke

Synesthesia and Migraine: Case Report

<p>Abstract</p> <p>Background</p> <p>Synesthesia is, as visual migraine aura, a common and fascinating perceptual phenomenon. Here we present a unique case with synesthesias exclusively during visual migraine auras.</p> <p>Case presentation</p> <p>A 40-year-old woman with a cyclic mood disorder had suffered from migraine with visual aura for several years. On several occasions she had experienced "mixing of senses" during the aura phase. Staring at strong bright light she could experience intense taste of lemon with flow from the salivary glands.</p> <p>Conclusion</p> <p>Acquired synesthesia, exclusively coincident with migraine aura, gives support to the idea of an anomalous cortical processing underlying the phenomenon.</p

Genetic epidemiology of amyotrophic lateral sclerosis in Norway - a 2-year population based study

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons. In Europe, disease-causing genetic variants have been identified in 40-70% of familial ALS patients and approximately in 5% of sporadic ALS patients. In Norway, the contribution of genetic variants to ALS has not yet been studied. In light of the potential development of personalized medicine, knowledge of genetic causes of ALS in a population is becoming increasingly important. The present study provides clinical and genetic data on familial and sporadic ALS patients in a Norwegian population-based cohort. Methods: Blood samples and clinical information from ALS patients were obtained at all 17 neurological departments throughout Norway during a 2-year period. Genetic analysis of the samples involved expansion analysis of C9orf72 and exome sequencing targeting 30 known ALS-linked genes. The variants were classified using genotype-phenotype correlations and bioinformatics tools. Results: A total of 279 ALS patients were included in the study. Of these, 11.5% had one or several family members affected with ALS, whereas 88.5% had no known family history of ALS. A genetic cause of ALS was identified in 31 individuals (11.1%), among which 18 (58.1%) were familial and 13 (41.9%) were sporadic. The most common genetic cause was the C9orf72 expansion (6.8%), which was identified in 8 familial and 11 sporadic ALS patients. Pathogenic or likely pathogenic variants of SOD1 and TBK1 were identified in 10 familial and 2 sporadic cases. C9orf72 expansions dominated in patients from the Northern and Central regions, whereas SOD1 variants dominated in patients from the South-Eastern region. Conclusion: In the present study, we identified several pathogenic gene variants in both familial and sporadic ALS patients. Restricting genetic analysis to only familial cases would miss more than 40 percent of those with a disease-causing genetic variant, indicating the need for genetic analysis in sporadic cases as well.publishedVersio

CONSORT recommendations in abstracts of randomised, controlled trials on migraine and headache

A CONSORT statement on the content of abstracts of randomised, controlled trials (RCTs) was published in 2008. I therefore reviewed the abstracts from 2009 to 2010 published on RCTs in Cephalalgia, Headache and other (non-headache) journals. The following items were reviewed: number of patients, reporting of response either in percentages or absolute values, the use of p values, and effect size with its precision. The latter was recommended in the CONSORT statement. A total of 46 abstracts were reviewed and effect size with 95% confidence intervals was only reported in seven abstracts. The influence of the CONSORT statement on reporting in abstracts has so far only had a limited influence on the headache literature

Cerebrospinal fluid sodium rhythms

Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF. Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the 24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations with potassium, protein, and osmolarity. Results: The distribution of sodium varied much more than potassium, and there were statistically significant rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity. Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may have additional repercussions on ultradian functions