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Background: The Vertigo Symptom Scale–short form (VSS–SF) is commonly used to measure dizziness and vertigo over the past month. This study aimed to (1) adapt the VSS–SF for the Swedish population and assess its psychometric properties, and (2) develop a modified version for measuring symptoms in the acute phase of acute vestibular syndrome (AVS).

Methods: The VSS–SF was translated into Swedish and adapted cross-culturally. Its psychometric properties were evaluated in 86 AVS patients, both in the acute stage (1–7 days from symptom onset) with a modified acute version, and after six weeks of vestibular rehabilitation using the standard VSS–SF. Factor structure, convergent and discriminant validity, and internal consistency were analyzed. Test-retest reliability was assessed at six weeks. Participants were also evaluated with the Dizziness Handicap Inventory (DHI) and balance tests. Controls included 54 healthy participants.

Results: Exploratory factor analysis revealed a two-factor structure for both versions, corresponding to vertigo-balance (VSS–V) and autonomic-anxiety (VSS–A) subscales. Both versions demonstrated strong factor structures with adequate loadings. Internal consistency was high for the standard version (Cronbach’s alpha 0.76 to 0.87) and for the total and VSS–V subscale of the acute version (0.82 and 0.85, respectively), but poor for the acute VSS–A subscale (0.50). Convergent validity was supported by Spearman’s rank correlations. The discriminative ability was excellent for the acute VSS–SF and VSS–V (AUC 0.98 and 0.99), and acceptable for VSS–A (AUC 0.77). After six weeks, discriminative ability decreased but remained above 0.5. Test-retest reliability at six weeks was excellent for all scales (ICC 0.94, 0.93, and 0.93 for VSS–SF, VSS–V, and VSS–A).

Conclusions: The VSS–SF was successfully adapted for the Swedish population, including an acute version for early dizziness assessment. Both versions confirmed a robust two-factor structure, with the acute version showing excellent early discriminative ability, particularly for the vertigo-balance dimension. However, the autonomic-anxiety subscale showed weaker psychometric properties, suggesting limited suitability for AVS patients. The adapted scales show promise for clinical use in diagnosing and evaluating dizziness and vertigo in the Swedish population.

Trial registration: Clinicaltrials.gov Identifier NCT05056324, September 24, 2021. https://clinicaltrials.gov/ct2/show/NCT05056324.

BACKGROUND: Vertigo and dizziness can be disabling symptoms that result in sick leave. Research regarding sickness absence due to dizziness has focused on specific vestibular diagnoses rather than the nonspecific vertigo/dizziness diagnoses. Strict sick leave regulations were introduced in Sweden in 2008. The aim of this study was to describe the vertigo/dizziness sick leave prevalence and duration considering both specific and nonspecific diagnoses according to International Classification of diseases 10th revision (ICD-10) on the 3-digit level, including the less specific "R" diagnoses.

METHODS: Through Swedish nationwide registers we identified individuals aged 16-64 years who during the years 2005-2018 were sickness absent > 14 consecutive days - minimum register threshold - due to vertigo/dizziness diagnoses according to ICD10 codes: specific diagnoses (H81.0, H81.1, H81.2, H81.3, H81.4, G11x) and nonspecific (R42, R26, R27, H81.9). We described the demographic characteristics, prevalence and duration of such sick-leave spells. Data were stratified according to diagnostic groups: ataxias, vestibular and nonspecific.

RESULTS: We identified 52,179 dizziness/vertigo sick leave episodes > 14 days in 45,353 unique individuals between 2005-2018, which constitutes 0.83% from all sick leave episodes in the given period.The nonspecific diagnoses represented 72% (n = 37741) of sick leave episodes and specific vestibular H-diagnoses 27% (n = 14083). The most common specific vestibular codes was Benign paroxysmal positional vertigo (BPPV) 9.4% (n = 4929). The median duration of sick leave was 31 days (IQR 21-61). Women on sick leave were younger than men (47 vs 51 years, p < 0.05) and had a higher proportion of nonspecific diagnoses compared with men (74% vs 70%, p < 0.05).

CONCLUSIONS: The vast majority of vertigo/dizziness sick leave episodes were coded as nonspecific diagnoses and occurred in women. BPPV, a curable vestibular condition, was the most common specific diagnosis. This suggests a potential for improved diagnostics. Women on sick leave due to dizziness/vertigo were younger and more often received nonspecific diagnostic codes. Future studies should determine the frequency of use of evidence based therapies and investigate further the gender differences.

Background: Patients with in-hospital stroke (IHS) are discovered and treated with delays compared to community-onset stroke. This qualitative study explores current routines and clinical practices for IHS in Sweden, aiming to uncover factors influencing management and propose areas for future research and development.

Methods: Six physicians in charge of stroke alerts at Swedish hospitals were individually interviewed in video calls. Informants were selected from The Swedish Stroke Register, based on the hospital-specific median processing time for delivering thrombolysis or thrombectomy to IHS patients, stratified by hospital size. Transcribed interviews were analysed using reflexive thematic analysis.

Results: Three main themes were developed. The first emphasized the crucial step of discovering IHS and outlined possible workflow pathways, including defining the “key player” with stroke expertise and mandate to proceed with the stroke alert to immediate radiology. Subsequent themes addressed obstacles to optimal practice and suggested clear guidelines for contacting the "key player” to reduce delays, as well as offering IHS education to hospital staff.

Conclusions: This study identified differences in workflows for IHS management across the six included sites. A "key player" emerged as a common denominator, who was called as the initiation of the stroke alert and had mandate to proceed with the alert to immediate radiology. Clear guidelines for contacting the “key player” and increased education about IHS were suggested as possible ways to mitigate delays to activate the stroke alert.

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.

A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).

Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).

In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.

Background and purpose: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood.

Methods: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated.

Results: The mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated.

Conclusions: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.

Synergistic interactions between human herpesvirus 6A (HHV-6A) and Epstein–Barr virus (EBV) are hypothesized in the etiopathogenesis of multiple sclerosis (MS). This study investigated if HHV-6A and EBV seroreactivities interact regarding the risk of developing MS. Antibodies against viral antigens were analyzed in biobank samples from 670 individuals who later developed MS and matched controls. Additive interactions were analyzed. A significant interaction between HHV-6A and EBNA-1 seroreactivities was observed in study participants above the median age of 24.9 years (attributable proportion due to interaction = 0.45). This finding supports the hypothesis that HHV-6A and EBV infections interact in MS development. ANN NEUROL 2024.

Background and purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk–benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.

Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed.

Results: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38–0.92) to 0.03 (95% CI 0.02–0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70–2.48) to 0.08 (95% CI 0.03–0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30–3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events.

Conclusion: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

Background: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of processing speed and physical disability after disease-modulating therapy (DMT) start.

Methods: Using a group-modelling approach, we assessed trajectories of processing speed with oral Symbol Digit Modalities Test (SDMT) and physical disability with Expanded Disability Status Scale, from first DMT start among 1645 patients with RRMS followed during 2011-2022. We investigated predictors of trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories.

Results: We identified 5 stable trajectories of processing speed: low SDMT scores (mean starting values=29.9; 5.4% of population), low/medium (44.3; 25.3%), medium (52.6; 37.9%), medium/high (63.1; 25.8%) and high (72.4; 5.6%). We identified 3 physical disability trajectories: no disability/stable (0.8; 26.8%), minimal disability/stable (1.6; 58.1%) and moderate disability (3.2; 15.1%), which increased to severe disability. Older patients starting interferons were more likely than younger patients starting rituximab to be on low processing speed trajectories. Older patients starting teriflunomide, with more than one comorbidity, and a history of pain treatment were more likely to belong to the moderate/severe physical disability trajectory, relative to the no disability one. There was a strong association between processing speed and physical disability trajectories.

Conclusions: In this cohort of actively treated RRMS, patients' processing speed remained stable over the years following DMT start, whereas patients with moderate physical disability deteriorated in physical function. Nevertheless, there was a strong link between processing speed and disability after DMT start.

INTRODUCTION: Few studies have reported the characteristics of patients with in-hospital stroke (IHS) including the reason for hospitalization and invasive procedures before the stroke. We aimed to extend current knowledge.

PATIENTS AND METHODS: All adult patients with IHS in Sweden during 2010-2019 registered in the Swedish Stroke Register (Riksstroke) were included. The cohort was cross-linked to the National Patient Register and data extracted on background diagnoses, main discharge diagnoses, and procedure codes for the hospitalization when IHS occurred and any hospital-based healthcare contacts within 30 days before IHS.

RESULTS: 231,402 stroke cases were identified of which 12,551 (5.4%) were in-hospital and had corresponding entries in the National Patient Register. Of the IHS patients, 11,420 (91.0%) had ischemic stroke and 1131 (9.0%) hemorrhagic stroke; 5860 (46.7%) of the IHS patients had at least one invasive procedure prior to ictus. 1696 (13.5%) had a cardiovascular procedure and 560 (4.5%) a neurosurgical procedure. 1319 (10.5%) patients only had minimally invasive procedures such as blood product transfusion, hemodialysis, or central line insertion. Common discharge diagnosis in patients with no invasive procedures were cardiovascular disorders, injuries, and respiratory disorders.

DISCUSSION AND CONCLUSION: One in every 17 strokes in Sweden occur in a hospital. In this unselected large cohort the previously reported major causes for in-hospital stroke, cardiovascular and neurosurgical procedures, preceded IHS in only 18.0% of cases suggesting that other etiologies are more common than previously reported. Future studies should aim at determining absolute risks of stroke after surgical procedures and ways of risk reduction.

Background: Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort.

Methods: Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors.

Results: Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4).

Conclusion: Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.