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

Transitorisk iskemisk attakk eller migreneaura?

Migraine or migraine-like symptoms can contribute to a delayed stroke diagnosis. However, migraine with aura is a common stroke mimic and often the basis for acute thrombolytic therapy. It is probably also the reason why many patients are misdiagnosed with a transient ischemic attack. In this clinical review, we explain the factors that could differentiate a transient ischemic attack from a migraine with aura.Migrene eller migrenelignende symptomer kan bidra til forsinket hjerneslagdiagnose. Imidlertid er migrene med aura en vanlig hjerneslagimitator og ikke sjelden årsak til akutt trombolytisk behandling. Sannsynligvis er det også årsak til at pasienter kan få en feilaktig diagnose med transitorisk iskemisk attakk. I denne kliniske oversikten redegjør vi for hva som kan skille et transitorisk iskemisk attakk fra et anfall med migreneaura

Visual inspection versus spectrophotometry for xanthochromia detection in patients with sudden onset severe headache—A diagnostic accuracy study

Objective - There is still disagreement about whether to routinely use spectrophotometry to detect xanthochromia in cerebrospinal fluid (CSF) or whether visual inspection is adequate. We aimed to evaluate the diagnostic accuracy of these methods in detecting an aneurysmal subarachnoid hemorrhage in patients with sudden onset severe headache. Background - When a patient presents to the emergency department with a headache for which there is suspicion of a subarachnoid hemorrhage, the gold standard to rule this out is to perform a CSF analysis for xanthochromia with or without spectrophotometry if the cranial non-contrast computed tomography (CT) upon admission is negative. Methods - Having applied the gold standard, we retrospectively included patients with acute headache who underwent both CT scan and CSF spectrophotometry at our hospital in the period 2002–2020. Patients were excluded if the cranial CT was interpreted as positive, there was a bloody CSF, or if visual assessment data of the CSF was unavailable. We scrutinized the patients’ medical records and evaluated the benefit of spectrophotometry compared to visual inspection. The net bilirubin absorbance cut-off for support of subarachnoid hemorrhage was set at >0.007 absorbance units. The spectrophotometry was also considered positive if the net bilirubin absorbance was ≤0.007 and net oxyhemoglobin absorbance was ≥0.1 absorbance units. We calculated and compared the sensitivity and specificity of CSF spectrophotometry and visual inspection of the CSF. Results - In total, 769 patients, with a mean age of 42.3 ± (standard deviation [SD] = 17.3) years, were included. The headache onset was classified as a thunderclap headache in 41.5%, and 4.7% had a sudden loss of consciousness. Fifteen patients (2%) were finally diagnosed with a subarachnoid hemorrhage, six (0.8%) had an aneurysmal subarachnoid hemorrhage, seven (0.9%) had a perimesencephalic hemorrhage, one (0.1%) had a cortical cerebral sinus venous thrombosis, and one (0.1%) had a spinal epidural hematoma. Four patients (0.5%) had a subarachnoid hemorrhage that was not detected by visual inspection, and two were caused by an aneurysmal rupture. One of these two patients died just before intervention, and the other underwent coiling for an anterior communicating aneurysm. The number needed for lumbar puncture to detect a subarachnoid hemorrhage was 51, but 128 to detect an aneurysmal hemorrhage. The corresponding numbers needed for CSF spectrophotometric analysis were 192 and 385, respectively. Spectrophotometry was positive in 31 patients (4.0%), of whom 18 (2.3%) also had visually detected xanthochromia (11 true positive). The mean net bilirubin absorbance in the 13 samples with visually clear CSF was 0.0111 ± (SD = 0.0103) absorbance units, compared to 0.0017 ± (SD = 0.0013) in the CSF with negative spectrophotometry. The corresponding figures for net oxyhemoglobin absorbance were 0.0391 ± (SD = 0.0522) versus 0.0057 ± (SD = 0.0081). The sensitivity of spectrophotometric xanthochromia detection was 100% (95% confidence interval [CI], 78–100), compared to 73% (95% CI, 45–92) for visual xanthochromia detection. The specificity of spectrophotometric xanthochromia detection was 98% (95% CI, 97–99) compared to 99% (95% CI, 98–100) for visual xanthochromia detection. Both methods had high negative predictive values: 100% (95% CI, 99.5–100) versus 99.5% (95% CI, 98.6–99.9), respectively. Conclusions - Both visual inspection and spectrophotometry have high diagnostic accuracy for detecting CSF xanthochromia, but the lower sensitivity of visual assessment makes it unreliable, and we recommend the use of spectrophotometry in clinical practice

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

Etablering av medisinske sannheter

publishedVersio

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

Amyotrophic lateral sclerosis caused by the C9orf72 expansion in Norway–prevalence, ancestry, clinical characteristics and sociodemographic status

Objective: The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the C9orf72 expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a C9orf72 expansion (C9pos). Further, we compared C9pos and C9neg patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status. Methods: We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The C9orf72 expansion was examined for all patients. Results: The study enrolled 500 ALS patients, 8.8% of whom were C9pos, with half being sporadic ALS cases. The proportion of C9pos cases differed between regions, ranging from 17.9% in the Northern region to 1.9% in the Western region. The majority of C9pos patients had non-Finnish European descent and were not closely related. C9pos patients exhibited a significantly shorter mean survival time, had a higher frequency of relatives with ALS or dementia, and were more often unmarried/single and childless than C9neg patients. Conclusion: C9pos patients constitute a large portion of the Norwegian ALS population. Ancestry and relatedness do not adequately explain regional differences. Relying on clinical information to identify C9pos patients has proven to be challenging. Half of C9pos patients were reported as having sporadic ALS, underlining the importance of carefully assessing family history and the need for genetic testing.publishedVersio