MS Akademie 2018 — 28.09. - 29.09.2018

In dieser Rubrik stellen wir Ihnen regelmäßig wichtige Beiträge österreichischer NeurologInnen zum internationalen wissenschaftlichen Fortschritt vor.
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November 2017

Prim.PD Dr. T.v.Oertzen

Prim.PD Dr. T.v.Oertzen

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

REF Link zur Originalpublikation

Autoren: Ingmar Blumcke, M.D., Roberto Spreafico, M.D., Ph.D., Gerrit Haaker, M.D., Roland Coras, M.D., Katja Kobow, Ph.D., Christian G. Bien, M.D., Margarete Pfäfflin, M.Sc., Christian Elger, M.D., Guido Widman, M.D., Johannes Schramm, M.D., Albert Becker, M.D., Kees P. Braun, M.D., Frans Leijten, M.D., Johannes C. Baayen, M.D., Eleonora Aronica, M.D., Ph.D., Francine Chassoux, M.D., Hajo Hamer, M.D., Hermann Stefan, M.D., Karl Rössler, M.D., Maria Thom, M.D., Matthew C. Walker, M.D., Sanjay M. Sisodiya, F.R.C.P., John S. Duncan, M.D., Andrew W. McEvoy, M.D., Tom Pieper, M.D., Hans Holthausen, M.D., Manfred Kudernatsch, M.D., H. Joachim Meencke, M.D., Philippe Kahane, M.D., Ph.D., Andreas Schulze-Bonhage, M.D., Josef Zentner, M.D., Dieter H. Heiland, M.D., Horst Urbach, M.D., Bernhard J. Steinhoff, M.D., Thomas Bast, M.D., Laura Tassi, M.D., Giorgio Lo Russo, M.D., Cigdem Özkara, M.D., Buge Oz, M.D., Pavel Krsek, M.D., Silke Vogelgesang, M.D., Uwe Runge, M.D., Holger Lerche, M.D., Yvonne Weber, M.D., Mrinalini Honavar, M.D., José Pimentel, M.D., Ph.D., Alexis Arzimanoglou, M.D., Adriana Ulate-Campos, M.D., Soheyl Noachtar, M.D., Elisabeth Hartl, M.D., Olaf Schijns, M.D., Renzo Guerrini, M.D., Carmen Barba, M.D., Thomas S. Jacques, F.R.C.Path., Ph.D., J. Helen Cross, F.R.C.P.C.H., Ph.D., Martha Feucht, M.D., Angelika Mühlebner, M.D., Thomas Grunwald, M.D., Ph.D., Eugen Trinka, M.D., Peter A. Winkler, M.D., Antonio Gil-Nagel, M.D., Ph.D., Rafael Toledano Delgado, M.D., Thomas Mayer, M.D., Martin Lutz, Ph.D., Basilios Zountsas, M.D., Kyriakos Garganis, M.D., Felix Rosenow, M.D., Anke Hermsen, M.Sc., Tim J. von Oertzen, M.D., Thomas L. Diepgen, M.D., Ph.D., and Giuliano Avanzini, M.D., for the EEBB Consortium*


Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy.

We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%).

The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients.

In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.)

September 2017

Christoph Waiß

Christoph Waiß

CXCL-13 as a biomarker in the diagnostics of neuroborreliosis

  Nervenarzt. 2017 Link zur Originalpublikation
Autoren: Waiß C.,Kindler W., Ströbele B., Aspöck C., Oberndorfer S.


BACKGROUND: The chemokine CXCL-13 is a potential intrathecal biomarker for neuroborreliosis (NB). According to the literature the sensitivity of CXCL-13 in the diagnostics of NB varies between 88% and 100% and the specificity between 63% and 99.7%. The objective of this study was to analyze the sensitivity and specificity of CXCL-13 in the diagnosis of NB in an endemic area of Borrelia burgdorferi.
MATERIAL AND METHODS: In a retrospective analysis of data from August 2014 to August 2016, 63 patients with clinically suspected NB were identified. The diagnosis of NB was based on the guidelines of the German Society of Neurology (DGN).
RESULTS: In 10 patients a definitive diagnosis of NB could be established (CXCL-13 min. 254 pg/ml /max. >900 pg/ml). The criteria for a probable NB were fulfilled by 2 patients (CXCL-13 concentration 8 pg/ml and 69 pg/ml, respectively), 9 patients had a chronic inflammatory demyelinating disease (CXCL-13 min. 10 pg/ml/max. 649 pg/ml) and 42 patients had other neurological diagnoses. Out of these, elevated intrathecal CXCL-13 concentrations were detected in 8 patients (e. g. tuberculosis, syphilis and anti-RI antibody positive paraneoplastic syndrome).
CONCLUSION: By increasing the CXCL-13 cut-off level from 20 pg/ml to 200 pg/ml, the diagnostic sensitivity for NB remains 100% and consequently the specificity increases from 69.8% to 92.4%. Moreover, a CXCL-13 cut-off set at 200 pg/ml would exclude NB in the 2 patients with probable NB. We conclude from these results that CXCL-13 represents a valuable biomarker for the exclusion of untreated NB, although with limited specificity.

Juli 2017

Anna Grisold

Anna Grisold

Chemotherapy-induced peripheral neuropathy: A current review.

  Ann Neurol. 2017 Jun;81(6):772-781. Link zur Originalpublikation
Autoren: Staff NP, Grisold A, Grisold W, Windebank AJ.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30 to 40% of patients treated with neurotoxic chemotherapy will develop CIPN, and there is considerable variability in its severity between patients.
copyright Wiley

copyright Wiley

It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents.

Juni 2017

Sonja Hochmeister

Sonja Hochmeister

Widespread cortical demyelination of both hemispheres can be induced by injection of pro-inflammatory cytokines via an implanted catheter in the cortex of MOG-immunized rats.

  Exp Neurol. 2017 Aug;294:32-44. Link zur Originalpublikation
Autoren: Üçal M, Haindl MT, Adzemovic MZ, Strasser J, Theisl L, Zeitelhofer M, Kraitsy K, Ropele S, Schäfer U, Fazekas F, Hochmeister S.

Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a fewdays. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats. After 14 days the rats were immunized with 5 μg myelin oligodendrocyte glycoprotein (MOG) in incomplete Freund’s Adjuvant, which did not cause any clinical signs but animals developed a stable anti-MOG antibody titer. Then the animals received an injection of proinflammatory cytokines through the catheter.
copyright elsevier

copyright elsevier

This led to a demyelination of cortical and subcortical areas starting from day 1 in a cone-like pattern spreading from the catheter area towards the subarachnoid space. On day 3 cortical demyelination already expanded to the contralateral hemisphere and reached its peak between days 9–15 after cytokine injection with a widespread demyelination of cortical and subcortical areas of both hemispheres. Clinically the animals showed only discrete signs of fatigue and recovered completely after day 15. Even on day 30 we stillwere able to detect demyelination in subpial and intracortical areas along with areas of partial and complete remyelination. Loss of cortical myelin was accompanied with marked microglia activation. A second injection of cytokines through the catheter on day 30 led to a second demyelination phase with the same symptoms, but again no detectable motor dysfunction. Suffering of the animals appeared minor compared to standard Experimental Autoimmune Encephalomyelitis and therefore, even long-term observation and repeated demyelination phases seem ethically acceptable.

Mai 2017

Milan Vosko

Milan R. Vosko

J Thromb Thrombolysis. 2017 Apr;43(3):306-317.

  J Thromb Thrombolysis. 2017 Apr;43(3):306-317. Link zur Originalpublikation
Autoren: Vosko MR, Bocksrucker C, Drwiła R, Dulíček P, Hauer T, Mutzenbach J, Schlimp CJ, Špinler D, Wolf T, Zugwitz D.

Non-vitamin K antagonist oral anticoagulants (NOACs) have a favorable benefit-risk profile compared with vitamin K antagonists. However, the lack of specific reversal agents has made the management of some patients receiving long-term treatment with NOACs problematic in emergency situations such as major bleeding events or urgent procedures. Idarucizumab, a fully humanized Fab antibody fragment that binds specifically and with high affinity to dabigatran, was recently approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effect is required. Clinical experience with idarucizumab is currently limited. We report 11 real-life clinical cases in which idarucizumab was used after multidisciplinary consultation in a variety of emergency situations including severe postoperative bleeding, emergency high-bleeding-risk surgery (hip/spine surgery and neurosurgery), invasive diagnostic testing (lumbar puncture), intracranial bleeding (pre-pontine subarachnoid hemorrhage and lobar intracerebral hemorrhage) and thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke. This case series illustrates the role of idarucizumab in improving patient safety in rare emergency situations requiring rapid reversal of the anticoagulant effect of dabigatran, while highlighting the importance of information and education about the availability and appropriate use of this recently approved specific reversal agent.

April 2017

Markus Leitinger

Markus Leitinger

Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study

  Lancet Neurol. 2016 Sep;15(10):1054-62. Link zur Originalpublikation
Autoren: Leitinger M, Trinka E, Gardella E, Rohracher A, Kalss G, Qerama E, Höfler J, Hess A, Zimmermann G, Kuchukhidze G, Dobesberger J, Langthaler PB, Beniczky S.

BACKGROUND: Several EEG criteria have been proposed for diagnosis of non-convulsive status epilepticus (NCSE), but none have been clinically validated. We aimed to assess the diagnostic accuracy of the EEG criteria proposed by a panel of experts at the fourth London-Innsbruck Colloquium on Status Epilepticus in Salzburg, 2013 (henceforth called the Salzburg criteria).
METHODS: We did a retrospective, diagnostic accuracy study using EEG recordings from patients admitted for neurological symptoms or signs to three centres in two countries (Danish Epilepsy Centre, Dianalund, Denmark; Aarhus University Hospital, Aarhus, Denmark; and Paracelsus Medical University, Salzburg, Austria). Participants were included from the Danish centres if they were aged 4 months or older, and from the Austrian centre if aged 18 years or older. Participants were sorted into two groups: consecutive patients under clinical suspicion of having NCSE (the clinical validation group) or consecutive patients with abnormal EEG findings but no clinical suspicion of NCSE (the control group). Two raters blinded to all other patient data retrospectively analysed the EEG recordings and, using the Salzburg criteria, categorised patients as in NCSE or not in NCSE. By comparing with a reference standard inferred from all clinical and para-clinical data, therapeutic response, and the final outcome, we calculated sensitivity, specificity, overall diagnostic accuracy, positive and negative predictive values, and inter-rater agreement for the Salzburg criteria. The reference standard was inferred by two raters who were blinded to the scorings of the Salzburg criteria.
FINDINGS: We retrospectively reviewed EEG data from 220 patients. EEGs in the clinical validation group were recorded in 120 patients between Jan 1, and Feb 28, 2014 (Austria), and Aug 1, 2014, and Jan 31, 2015 (Denmark). EEGs in the control group were recorded in 100 patients between Jan 13 and Jan 22, 2014 (Austria) and Jan 12 and Jan 26, 2015 (Denmark). According to the reference standard, 43 (36%) of the 120 patients in the validation group had NCSE. In the validation cohort sensitivity was 97·7% (95% CI 87·9-99·6) and specificity was 89·6% (80·8-94·6); overall accuracy was 92·5% (88·3-97·5). Positive predictive value was 84·0% (95% CI 74·1-91·5) and negative predictive value was 98·6% (94·4-100). Three people in the control group (n=100) fulfilled the Salzburg criteria and were therefore false positives (specificity 97·0%, 95% CI 91·5-99·0; sensitivity not calculable). Inter-rater agreement was high for both the Salzburg criteria (k=0·87) and for the reference standard (k=0·95). Therapeutic changes occurred significantly more often in the group of patients fulfilling Salzburg criteria (42 [84%] of 50 patients) than in those who did not (11 [16%] of 70; p<0·0001).
INTERPRETATION: The Salzburg criteria for diagnosis of NCSE have high diagnostic accuracy and excellent inter-rater agreement, making them suitable for implementation in clinical practice.

März 2017

Walter Pirker

Walter Pirker

Gait disorders in adults and the elderly: A clinical guide.

  Wien Klin Wochenschr. 2017 Feb;129(3-4):81-95. Link zur Originalpublikation
Autoren: Pirker W, Katzenschlager R

Human gait depends on a complex interplay of major parts of the nervous, musculoskeletal and cardiorespiratory systems. The individual gait pattern is influenced by age, personality, mood and sociocultural factors. The preferred walking speed in older adults is a sensitive marker of general health and survival. Safe walking requires intact cognition and executive control. Gait disorders lead to a loss of personal freedom, falls and injuries and result in a marked reduction in the quality of life. Acute onset of a gait disorder may indicate a cerebrovascular or other acute lesion in the nervous system but also systemic diseases or adverse effects of medication, in particular polypharmacy including sedatives. The prevalence of gait disorders increases from 10 % in people aged 60-69 years to more than 60 % in community dwelling subjects aged over 80 years. Sensory ataxia due to polyneuropathy, parkinsonism and frontal gait disorders due to subcortical vascular encephalopathy or disorders associated with dementia are among the most common neurological causes. Hip and knee osteoarthritis are common non-neurological causes of gait disorders. With advancing age the proportion of patients with multiple causes or combinations of neurological and non-neurological gait disorders increases. Thorough clinical observation of gait, taking a focused patient history and physical, neurological and orthopedic examinations are basic steps in the categorization of gaitdisorders and serve as a guide for ancillary investigations and therapeutic interventions. This clinically oriented review provides an overview on the phenotypic spectrum, work-up and treatment of gait disorders.

Februar 2017


Peter Sommer

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

  J Neurol. 2017 Jan;264(1):131-138. Link zur Originalpublikation
Autoren: Sommer P, Seyfang L, Posekany A, Ferrari J, Lang W, Fertl E, Serles W, Töll T, Kiechl S, Greisenegger S

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.