Klaus Berek

Background: The relationship between intrathecal kappa free light chain (κ‐FLC) synthesis and retinal layer atrophy in multiple sclerosis (MS) is unknown. Objective: To investigate whether the κ‐FLC index is associated with peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thickness. Methods: Patients with newly diagnosed clinically isolated syndrome or relapsing MS and available cerebrospinal fluid (CSF) analysis and optical coherence tomography (OCT) were included. Clinical and magnetic resonance imaging (MRI) data were also assessed. κ‐FLC concentrations were measured by nephelometry, and the κ‐FLC index was calculated as (CSF κ‐FLC/serum κ‐FLC)/albumin quotient. Results: A total of 100 patients at a median age of 33 (25th–75th percentile: 25–39) years and a female predominance (58%) were included. In multivariable linear regression analysis adjusted for age, sex, disease duration, number of T2‐hyperintense and number of contrast‐enhancing MRI lesions, the κ‐FLC index was associated with pRNFL (log‐transformed κ‐FLC index: β : −2.51; 95% confidence interval [CI]: −4.01, −1.01; p = 0.001) and GCIPL thinning (log‐transformed κ‐FLC index: β : −1.24, 95% CI: −2.32, −0.17; p = 0.024). Conclusions: Intrathecal plasma cell activity, as measured by the κ‐FLC index, is associated with neuroaxonal damage, as reflected by pRNFL and GCIPL atrophy.

Background: The prognostic value of κ-free light chain (κ-FLC) index over the long term is unknown. Objectives: The objective of the study was to determine whether κ-FLC index determined at disease onset predicts relapse activity and disability accrual during long-term follow-up. Methods: Patients with a first demyelinating event of the central nervous system who had cerebrospinal fluid and serum sampling were eligible for inclusion. At baseline, demographics, clinical data, number of T2 hyperintense (T2L) and contrast-enhancing lesions (CEL) on MRI were assessed. During follow-up occurrence of relapses, Expanded Disability Status Scale (EDSS) scores and disease-modifying treatments (DMT) were registered. κ-FLC was measured by nephelometry and κ-FLC index calculated as (CSF κ-FLC/serum κ-FLC)/albumin quotient. Results: Sixty-four patients with a median age at onset of 32 years (25th−75th percentile: 27−39) and a female predominance of 75% were followed over a median of 113 (90−129) months. Forty-six (72%) patients experienced relapse, 30 (47%) showed disability accrual. Multivariable Cox regression analysis adjusted for age, sex, disease duration, T2L, CEL and DMT revealed that κ-FLC index independently predicts time to relapse (per increase of 10: hazard ratio (HR) = 1.04, lower limit (LL)-confidence interval (CI) = 1.001, p = 0.044) and disability accrual (per increase of 10: HR = 1.05, LL-CI = 1.009, p = 0.022). Conclusions: κ-FLC index predicts long-term disease activity independently of other risk factors.

Background: Reduced bone mass and increased osteoporosis risk are common in people with multiple sclerosis (pwMS). The aim of the study was to identify risk factors for short‐term bone loss in MS.Methods: This prospective study included 139 pwMS (ages 18–65). Baseline data included demographics, body‐mass index, physical activity, smoking, menopause status, 25‐hydroxy vitamin D levels, and history of glucocorticoid use. Bone mineral density (BMD) was measured at baseline and after 2 years using dual‐energy X‐ray absorptiometry (DXA) for the lumbar spine and hip. Disability worsening was assessed by the Expanded Disability Status Scale (EDSS). Additionally, a literature review was conducted on longitudinal data regarding BMD in MS.Results: Over the 2‐year follow‐up period, significant BMD loss was observed in the hip (baseline g/cm²: median 0.898; IQR 0.808–1.014; 2‐year follow‐up: 0.882; 0.784–1.01; p < 0.001), but not in the lumbar spine. Overall, 101 (73.1%) experienced hip BMD loss, with a median decrease of 3.5%. Patients with disability worsening had an approximately 7‐times higher risk of bone loss compared to those without disability worsening (p = 0.013). PwMS with fractures during the follow‐up period had significantly lower hip BMD (0.760, 0.546–0.890 vs. 0.909, 0.828–1.015; p = 0.024), a higher EDSS score (4.4, 2.8–5.8 vs. 2.0, 1.0–4.0 vs. p = 0.026), and were older (59, 46–62 vs. 47, 37–54; p = 0.030) compared to those without fractures.Conclusion: Disability worsening was identified as a risk factor for BMD loss. These findings underscore the need for active monitoring of pwMS with disability worsening to prevent bone loss and, thus, to reduce fracture risk.

Introduction: Prognostication after subarachnoid hemorrhage (SAH) is essential to guide clinical management and improve patient care.Objective: To investigate whether decay rates of cerebrospinal fluid (CSF) red blood cells (RBC) and total protein (TP) after SAH predict functional outcome at 3 months.Methods: Patients with SAH treated at the Neurological Intensive Care Unit Innsbruck with a first CSF sample (CSFfirst) within 72 h after admission and at least one subsequent sample were eligible for inclusion. Decay rates of RBC and TP were measured between CSFfirst and each subsequent measurement (Weeks 1–3). Modified Rankin Scale scores at 3 months ≤ 2 were defined as good functional outcomes.Results: A total of 97 patients with a median age of 61 years [25th; 75th percentile: 52;71] and a median Hunt and Hess score of 4 [3;5] were included. Daily RBC decay rates decreased over time, while daily TP decay rates were highest in Week 1, showed a nadir in Week 2, and increased again in Week 3. In multivariable analysis, higher RBC (adjusted odds ratio (adjOR): 1.13, 95% confidence interval (95% CI): 1.02–1.26, p = 0.025) and TP (adjOR: 1.01, 95% CI: 1.00–1.01, p = 0.031) decay rates at Week 3 predicted a good functional outcome at Month 3. RBC and TP decreasing below 1180 cells/μL and 127.5 mg/dL, respectively, at Week 3 were associated with good functional outcome at Month 3 (adjOR: 11.04, 95% CI: 3.21–38.02, p < 0.001 and 6.03, 1.68–21.67, p = 0.006).Conclusions: Decay rates of CSF RBC and TP after SAH are associated with functional outcomes.

Background: Recognizing familiar faces and identifying emotions through facial expressions are essential for social functioning. This study aimed to examine whether people with relapsing-remitting multiple sclerosis (PwMS) differ from healthy control individuals (HC) in their performance on different tasks related to facial emotion processing. Methods: In a cross-sectional controlled study, 30 PwMS and 35 HC completed a baseline neuropsychological evaluation and experimental tasks assessing visual exploration of facial stimuli through eye tracking, facial emotion recognition, and facial memory recognition. The facial stimuli displayed either a neutral expression or an emotion (happiness, fear, or disgust). Results: PwMS and HC performed comparably in facial emotion recognition. In facial memory recognition, HC were significantly more accurate in recognizing previously seen fearful faces compared to neutral faces (Wilcoxon test, Z = -2.26, P = 0.024), demonstrating emotional enhancement of memory. In contrast, PwMS did not exhibit a memory advantage for fearful faces over neutral faces (P > 0.05). Groups also differed in the eye-tracking task. In all but one condition (disgust), PwMS showed a significantly greater tendency to explore the eye area rather than the mouth area compared to HC. Conclusions: Changes in visual exploration and a lack of emotional enhancement of memory are observed in PwMS, who otherwise demonstrate intact facial emotion recognition. These results suggest altered emotion-cognition interactions in PwMS. Early detection of subtle changes and targeted interventions may help prevent future debilitating impairments in social functioning.

Introduction: Lumbar puncture (LP) is a routine clinical procedure and, in some cases, is repeatedly performed for diagnostic or therapeutic reasons. The impact of repeated LP on cerebrospinal fluid (CSF) findings is not clear.Objective: To investigate whether repeated LP is associated with reactive pleocytosis and disruption of blood–CSF barrier function and to determine the role of interval between repeated LP.Methods: Patients with non‐inflammatory neurological disease (NIND) and at least two consecutive LP were included. Longitudinal changes in CSF white blood cell count (WBC), CSF total protein (TP), and CSF/serum albumin quotient (Q_alb) were assessed depending on the time interval between the LP.Results: A total of 73 patients with a median age of 35 years (25th–75th percentile: 25–45) and a female predominance of 75% had second LP after 6 (3–19) days. Twenty (27%) patients developed pleocytosis with an increase of WBC count to 8/μl (6–15) with a maximum of 30/μl. Patients with pleocytosis had the follow‐up LP significantly earlier than patients without pleocytosis, 3.5 (3–7) versus 7 (3–28) days. The majority of patients (90%) with CSF pleocytosis had the second LP within 10 days. Further repeated LP in a subgroup of patients revealed similar findings. CSF TP and Q_alb slightly increased in patients with pleocytosis.Conclusion: Mild “reactive” CSF pleocytosis occurred in approximately one‐third of patients after repeated LP, mostly when performed within 10 days.

Objective: To investigate the impact of transition interval length when switching from natalizumab (NTZ) to anti‐CD20 monoclonal antibodies (antiCD20) on recurrent disease activity and safety in relapsing multiple sclerosis (RMS).Methods: Aggregating data from 8 MS centres in Austria, Switzerland, and Germany, we included RMS patients who (i) continuously received NTZ for ≥3 months, (ii) were switched to antiCD20, and (iii) had ≥12 months follow‐up after switch. The primary endpoint was occurrence of relapse after switch, secondary endpoints included severe infections (CTCAE grade ≥3).Results: Overall, 139 RMS patients were included (70.5% females, mean age at switch 38.8 years [SD 9.7], mean disease duration at switch 11.3 years [SD 6.2], median duration on NTZ 4.4 years [range: 0.3–16.4], median transition interval 58 days [0–180]). Relapse occurred in 18 patients (12.9%) after NTZ discontinuation. Of those, 11 (61.1%) patients relapsed during the transition interval. No patient with a transition interval below 30 days experienced a relapse, compared to 11.1% and 16.1% with transition intervals of 30–44 days and ≥ 45 days, respectively. In multivariable Cox regression, a transition interval ≥ 45 days predicted a 4.73‐fold increased risk of relapse. Over approximately 4 years of follow‐up, six severe infections were reported without any noticeable effect of transition interval length. No PML occurred.Conclusions: Switching from NTZ to antiCD20 is generally both effective and safe. Keeping the transition interval below 30 days provides the optimal balance between preventing recurrent disease activity and ensuring safety.

Background: Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage.Objective: To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occurrence of AMS, and might be mitigated by preacclimatization.Methods: Healthy subjects were exposed to simulated high altitude (4500 m) by the use of a normobaric hypoxic chamber at the University of Innsbruck two times, that is, within Cycle 1 (C1) over 12 h, and within Cycle 2 (C2) for another 12 h but with a random assignment to prior acclimatization or sham acclimatization. Before each cycle (measurement [M] 1 and 3) and after each cycle (M2 and M4), clinical data (arterial oxygen saturation [SaO₂], heart rate, and Lake Louise AMS score [LLS]) and plasma samples were collected. pNfL was measured using single‐molecule array (Simoa) technique.Results: pNfL levels did not significantly change within each study cycle, but increased over the total study period (M1: 4.57 [3.34–6.39], M2: 4.58 [3.74–6.0], M3: 5.64, and M4: 6.53 [4.65–7.92] pg/mL, p < 0.001). Subjects suffering from AMS during the study procedures showed higher pNfL levels at M4 (6.80 [6.19–8.13] vs. 5.75 [4.17–7.35], p = 0.048), a higher total pNfL increase (2.88 [1.21–3.48] vs. 0.91 [0.53–1.48], p = 0.022) compared to subjects without AMS. An effect of preacclimatization on pNfL levels could not be observed.Conclusions: pNfL increases alongside exposure to simulated altitude and is associated with AMS.

Background and Purpose: Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis.Methods: Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real‐world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBC_first, TP_first), in Week 1 (RBC_Days1–7, TP_Days1–7), Week 2 (RBC_Days8–14, TP_Days8–14), and Week 3 or thereafter (RBC_Day>14, TP_Day>14), the highest detected value (RBC_highest, TP_highest), as well as the RBC count adjusted for disease duration (RBC_adjusted) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival.Results: A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50–70) years and median (IQR) Hunt and Hess score of 4 (3–5) were included. Multivariable analyses revealed that lower values of RBC_first, RBC_adjusted, RBC_highest, TP_first and TP_highest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival.Conclusions: Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real‐world cohort of SAH patients requiring external ventricular drainage.

Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome. Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses. A total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given ≥3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with ≥3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%. In our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred. This study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with ≥3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.