Multiple sclerosis in the elderly: a retrospective cohort study.

BACKGROUND: There is a lack of knowledge of disease course, prognosis, comorbidities and potential treatments of elderly MS patients. OBJECTIVE: To characterize the disease course including disability progression and relapses, to quantify the use of DMTs and to identify comorbidities and risk factors for progression in elderly multiple sclerosis (MS) patients. METHODS: This is a retrospective study of 1200 Austrian MS patients older than 55 years as of May 1st, 2017 representing roughly one-third of all the MS patients of this age in Austria. Data were collected from 15 MS centers including demographics, first symptom at onset, number of relapses, evolvement of disability, medication, and comorbidities. RESULTS: Median observation time was 17.1 years with 957 (80%) relapsing and 243 (20%) progressive onsets. Average age at diagnosis was 45 years with a female predominance of 71%. Three-hundred and twenty-six (27%) patients were never treated with a DMT, while most treated patients received interferons (496; 41%) at some point. At last follow-up, 420 (35%) patients were still treated with a DMT. No difference was found between treated and never-treated patients in terms of clinical outcome; however, patients with worse disability progression had significantly more DMT switches. Pyramidal onset, number of comorbidities, dementia, epilepsy, and psychiatric conditions as well as a higher number of relapses were associated with worse outcome. The risk of reaching EDSS 6 rose with every additional comorbidity by 22%. In late and very-late-onset MS (LOMS, VLOMS) time to diagnosis took nearly twice the time compared to adult and early onset (AEOMS). The overall annualized relapse rate (ARR) decreased over time and patients with AEOMS had significantly higher ARR compared to LOMS and VLOMS. Four percent of MS patients had five medications or more fulfilling criteria of polypharmacy and 20% of psychiatric drugs were administered without a matching diagnosis. CONCLUSIONS: In this study, we identified number of comorbidities, pyramidal and cerebellar signs, and a higher number of relapses as unfavorable prognostic factors in elderly MS patients filling gaps of knowledge in patients usually underrepresented in clinical trials and may guide future therapeutic studies.

Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study.

BACKGROUND/OBJECTIVE: The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria. METHODS: Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome. RESULTS: As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11. CONCLUSIONS: The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.

Thrombectomy in basilar artery occlusion.

BACKGROUND AND PURPOSE: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. METHODS: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0-2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). RESULTS: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0-2: 1.19; 95% confidence interval (CI) = 0.78-1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3-6 (odds ratio (OR) = 3.97; 95% CI = 1.32-11.94; p = 0.01) as compared to ACLVO. CONCLUSION: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.

[Guideline S1: Long COVID: Diagnostics and treatment strategies]. / Leitlinie S1: Long COVID: Differenzialdiagnostik und Behandlungsstrategien.

This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV­2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.

Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)]. / Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).

Complete and incomplete recurrent laryngeal nerve injury after thyroid and parathyroid surgery: Characterizing paralysis and paresis.

BACKGROUND: Injury of the recurrent laryngeal nerve and consequent disorder of vocal fold movement is a typical complication in thyroid and parathyroid surgery. During postoperative laryngoscopy we observed not only a complete standstill (vocal fold paralysis), but also a hypomobility (paresis). In this prospective study, we investigated the difference in incidence and prognosis as well as risk-factors, intraoperative neuromonitoring, and symptoms between vocal fold paralysis and vocal fold paresis. METHODS: Data were prospectively collected and analyzed in a single high-volume thyroid center between 2012 and 2016. Vocal fold paresis was defined as hypomobility in abduction or adduction, a reduction in range and speed of vocal fold movement. Vocal fold paralysis was defined as asymmetry and missing purposeful vocal fold movement. RESULTS: The study included 4,707 surgeries and 7,992 at-risk nerves at risk. Vocal fold paralysis was diagnosed in 374 patients (4.68% of 7,992 nerves at risk) and vocal fold paresis in 114 patients (1.43%). Exclusively in the paralysis group, 36 patients (0.45%) developed permanent loss of vocal fold function (P < .001). In follow-up, vocal fold paresis patients regain normal vocal fold function significantly earlier than vocal fold paralysis (mean duration: 6.96 ± 6.506 vs 10.77 ± 7,827 weeks) and presented with significantly less symptoms like hoarseness, diplophonia, dysphagia, and dyspnea (68.8% vs 95.9 %). In intraoperative neuromonitoring, vocal fold paresis showed a significantly higher postresectional N. vagus amplitude than vocal fold paralysis patients (0.349 mV vs 0.114 mV, P < .001). CONCLUSION: After thyroidectomy, vocal fold paresis must be distinguished from vocal fold paralysis and should be implemented as a separate outcome parameter in the postoperative quality assessment.

Can pulmonary sarcoidosis trigger a progressive multifocal leukoencephalopathy? Considerations from a case series and a review of literature.

Progressive multifocal leukoencephalopathy (PML) is a severe infectious brain disease with lethal outcome mainly seen in immunocompromised subjects. Herein, we describe a new form of PML with different outcome which was observed in patients suffering from systemic sarcoidosis. Thus, we raise the question whether preexisting sarcoidosis might predispose for or even trigger PML.

Is Functional Outcome Different in Posterior and Anterior Circulation Stroke?

Background and Purpose- Posterior circulation stroke (PCS) account for 20% of all ischemic strokes. There is limited evidence whether functional outcome of PCS is comparable to that of anterior circulation stroke (ACS). We aimed to analyze whether 3-month functional outcome is different in PCS and ACS. Methods- Patients with acute ischemic stroke prospectively enrolled within the Austrian Stroke Unit Registry were stratified by infarct localization according to the Oxfordshire Community Stroke Project Classification. Propensity score matching was used to control for covariate imbalances and to match patients with PCS and ACS. Patients were matched for stroke severity, recombinant tissue-type plasminogen activator treatment, and demographic and vascular risk factors. Main outcomes were the distribution of modified Rankin Scale after 3 months and multiple proportional odds models to estimate the influence of the infarct localization on the functional outcome. Results- From a total of 90 484 patients enrolled within the Austrian Stroke Unit Registry, 9208 (4604 PCS/4604 ACS) were matched, of those 954 (477 in each group) were treated with recombinant tissue-type plasminogen activator. We detected a significant shift towards better 3-month functional outcome in patients with ACS compared with PCS (odds ratio [OR], 1.19; 95% CI, 1.1-1.28; P<0.0001). In particular, functional outcome was worse in PCS with onset-to-door-time >270 minutes (OR, 1.34; 95% CI, 1.17-1.54; P<0.0001) and in PCS with unknown onset-to-door-time (OR, 1.26; 95% CI, 1.13-1.42; P<0.0001); however, we did not detect any difference in functional outcome between ACS and PCS in patients with an onset-to-door-time ≤270 minutes (1-180 minutes: OR, 0.92, 95% CI, 0.78-1.09, P=0.3554; 181-270 minutes: OR, 1.04, 95% CI, 0.79-1.37, P=0.7689). In patients treated with recombinant tissue-type plasminogen activator, functional outcome was not significantly different between PCS and ACS. Conclusions- PCS was associated with worse outcome compared with ACS in patients arriving later than 4.5 hours at hospital or in those with unknown onset of symptoms. Our results urge for implementation of symptoms found in the posterior circulation into preclinical patient-triage tools.

Prehospital and intra-hospital time delays in posterior circulation stroke: results from the Austrian Stroke Unit Registry.

Therapeutic effect of recombinant tissue-plasminogen activator (rt-PA) is time dependent. There is limited evidence whether localization of stroke within the posterior circulation (PCS) is associated with a treatment delay. We aimed to analyze within a nationwide multicenter cohort whether duration of pre- and intra-hospital patient management differs between patients with PCS and anterior circulation strokes (ACS). We studied onset-to-door-times (ODT) and door-to-needle-times (DNT) of all patients with acute ischemic stroke (IS) enrolled in the Austrian Stroke Unit Registry according to infarct localization. Classification into PCS and ACS was based on clinical presentation applying the criteria used in the Oxfordshire Community Stroke Project. Relationships between ODT, respectively, DNT and explanatory variables were modeled by multivariate linear regression. Between 2003 and 2015, 71010 patients with IS were enrolled, 11,924 with PCS and 59,086 with ACS. Overall, the ODT was significantly longer in PCS: median (IQR): 170 (25th, 75th‰: 79,420) min versus 110 (60,240); p < 0.001; this finding held true in multivariable analysis. In 10535 rt-PA-treated patients (1022 PCS/9832 ACS), ODT and DNT were significantly longer among those with PCS: ODT: median: 80 min (55,120) versus 72 (50,110), p < 0.001; DNT: 57 (35.90) versus 45 (30.67), p < 0.001. In the multivariate model, PCS was significantly associated with delay in the DNT. In conclusion, in this large nationwide cohort, patient management was significantly slower in PCS as compared to ACS. Increasing awareness about these delays and further elaboration of the underlying causes may translate into higher proportions of patients with PCS receiving rt-PA.

Predictive value of ABCD2 and ABCD3-I scores in TIA and minor stroke in the stroke unit setting.

OBJECTIVE: It is not clear whether risk scores for early stroke recurrence after TIA that have been mainly established in outpatient and emergency department settings are valid on the background of highly specialized stroke unit care. METHODS: ABCD2 and ABCD3-I scores have been prospectively documented in a cohort of patients admitted to Austrian stroke units within 24 hours of symptom onset with TIA or minor stroke (NIH Stroke Scale score <4). RESULTS: A total of 5,237 TIA and minor stroke patients met inclusion criteria, with 3-month follow-up data available on 2,457. Early and 3-month stroke were observed in 2.4% and 4.2% of the study population. The probability of early stroke during the stroke unit stay (median 2 [interquartile range 1-3] days) steadily increased from 0% to 4.8% and 0% to 16.7% with increasing ABCD2 and ABCD3-I score points, respectively. On 3-month follow-up, stroke risk increased from 0% to 8.0% and 0% to 23.8% with increasing ABCD2 and ABCD3-I score points, respectively. Of the individual score components, age, blood pressure, and diabetes were not related to early or 3-month stroke, whereas clinical presentation (C), symptom duration (D), and cerebral as well as carotid imaging (I) were and accounted for the information provided by the full scores. CONCLUSIONS: Standard ABCD2 and ABCD3-I scores are useful instruments to estimate the probability of early and 3-month stroke in TIA and minor stroke patients treated at specialized stroke units, with C, D, and I being the most important score components in this setting.

Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people.

BACKGROUND: In 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment. METHODS: (1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship. RESULTS: All 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians. CONCLUSIONS: A nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.

Spinal cord lesions in patients with neuromyelitis optica: a retrospective long-term MRI follow-up study.

Neuromyelitis optica (NMO) is characterised by a particular pattern of the optic nerves and the spinal cord. Long-term MRI follow-up studies of spinal NMO lesions are rare, or limited by short observation periods. In nine patients with definite NMO or recurrent longitudinally extensive transverse myelitis (LETM) with NMO-IgG serum antibodies, repeated MRI examinations of the spine were carried out over a period of up to 11 years and evaluated regarding the changes over time in this retrospective study. In eight patients spinal cord lesions were located centrally, involving the grey and white matter. In the first examination after clinical onset changes resembled a stroke of the anterior spinal artery in two patients. Symmetrical signal alterations within the grey matter were observed. In one patient this pattern was transient, but it remained in the other. During the chronic stage, either a variable degree of spinal cord atrophy and high signal alterations, or almost complete remission of the lesions, was observed. Spinal MRI of patients with NMO myelitis can resemble a stroke. MRI of acute NMO stages did not allow a prediction of the clinical outcome. To a variable degree, NMO left behind typical defects which correlated with the clinical outcome.

[Subcutaneous interferon-beta-1a in the treatment of multiple sclerosis]. / Interferon-Beta-1a subkutan in der Behandlung der Multiplen Sklerose.

During the last 10 years recombinant interferon-beta-1a administered subcutaneously has been the subject of several clinical trials in relapsing remitting multiple sclerosis (RRMS), in secondary progressive MS (SPMS), as well as in clinically isolated syndromes. All of them met the criteria of evidence level class I. Consistent evidence for moderate immunomodulatory effects on clinical parameters of disease activity was gained, and even higher efficacy of IFN-beta-1a sc. on MRI activity of multiple sclerosis was proven. Indirect evidence confirmed the hypothesis of a dose-response curve for IFN-beta-1a formulations in MS. The higher efficacy of IFN-beta-1a 44 microg sc. TIW, however, also includes more adverse events such as injection site reactions, flu-like symptoms and a moderate immunogenicity. Current evidence does not allow a recommendation of IFN-beta-1a sc. as most effective first line therapy, because also the individual patient's choice in the route of administration and long-term effects of neutralizing antibodies to IFN-beta-1a sc. must be taken into account. In the long-term, IFN-beta-1a showed a beneficial safety-tolerability profile with 50 % of patients sticking to the initial immunomodulatory treatment. There were no teratogenic effects, IFN-beta-1a sc. did not enhance depressive symptoms. Data on inhibition of the progression of disease, however, remained inconclusive. Probable beneficial effects of IFN-beta-1a sc. on cognitive function or "chronic fatigue" have not been investigated yet.