Correct Outcome Prognostication via Sonographic Volumetry in Supratentorial Intracerebral Hemorrhage

Introduction: The intracerebral hemorrhage (ICH)-score is used for estimation of patients' prognosis. The hemorrhage volume calculated from computed tomography (CT) contributes as one main factor. Several studies have proven that dimensions of an ICH may be displayed sufficiently by transcranial sonography (TCS). Yet, the adequacy of ICH-volumetry via TCS in calculating the ICH-score and its use as prognostic tool has not been studied.Methods: Forty consecutive patients with supratentorial ICH diagnosed via CT were included in this prospective observational pilot study. 45 examination-series via CT and TCS were done in order to perform an ICH-volumetry and calculate the ICH-score. Volume was calculated using the ABC/2 estimation. Results of both imaging techniques were compared regarding quantification of ICH- volume and correct prognostication. A modified Rankin Scale (mRS)-score of 0–3 points was valued as good outcome.Results: The imaging techniques did not show a difference in volumetry (p = 0.794) and TCS derived hemorrhage volume correlated significantly with ICH-volume measured on CT-scans. Calculated ICH-scores also did not differ (p = 0.323). Patients with an ICH-score larger than 2 points were predicted to experience a poor outcome at discharge with mRS 4–6 points, and the prognostication of the outcome was correct. Patients with a good outcome showed a smaller ICH-volume (11.2 ± 9.1ml) than patients with a poor outcome (38.2 ± 41.2 ml; p = 0.002).Conclusion: Volumetry in supratentorial ICH via TCS is feasible and the prognostication with the ICH-score based on its results is comparable to CT-imaging and sufficient

Studienprotokoll: Register zur Prognose akut-symptomatischer Anfälle (PROSA-Register) – eine prospektive multizentrische Beobachtungsstudie

Background: Acute symptomatic epileptic seizures occur in close temporal relation to an acute disturbance of brain function. They are associated with a low risk of subsequent unprovoked seizures; thus, current guidelines recommend not to administer a long-term antiseizure medication; however, in clinical practice long-term secondary seizure prophylaxis is frequently initiated. The seizure prognosis after guideline-conform untreated or only briefly treated acute symptomatic seizures, is so far unknown. Hypothesis: Following an acute symptomatic first epileptic seizure of structural etiology, the 1-year risk of subsequent unprovoked seizures is not higher than 25%, even if antiseizure medication was not applied or for a short period only. Methods: The PROSE register is a single-arm, open, prospective, multicenter observational study. A total of 115 subjects aged 18 years or older with an acute symptomatic first epileptic seizure of structural etiology will be included if the seizure was not a status epilepticus. Intrahospital follow-up will be based on the hospital records. Telephone follow-up interviews will be conducted 3, 6, and 12 months after the acute symptomatic seizure. Discussion: The PROSE register will shed light on current treatment practice of acute symptomatic seizures and the actual seizure outcome within 1 year. The results are assumed to support the current evidence that giving antiseizure medication for a longer period of time exceeding the acute phase of the underlying condition is unnecessary

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation

Background We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). Methods This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018. Results We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. Conclusions Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge

Seronegative myasthenic crisis: a multicenter analysis

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10–15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study. We identified 15 seronegative MG patients with 17 MCs and 142 AChR-MG with 159 MCs. Seronegative MCs were younger (54.3 ± 14.5 vs 66.5 ± 16.3 years; p = 0.0037), had a higher rate of thymus hyperplasia (29.4% vs 3.1%; p = 0.0009), and were more likely to be female (58.8% vs 37.7%; p = 0.12) compared to AChR-MCs. Time between diagnosis of MG and MC was significantly longer in seronegative patients (8.2 ± 7.6 vs 3.1 ± 4.4 years; p < 0.0001). We found no differences in duration of mechanical ventilation (16.2 ± 15.8 vs 16.5 ± 15.9 days; p = 0.94) and length of stay at intensive care unit (17.6 ± 15.2 vs 17.8 ± 15.4 days; p = 0.96), or in-hospital mortality (11.8% vs. 10.1%; p = 0.69). We conclude that MC in seronegative MG affects younger patients after a longer period of disease, but that crisis treatment efficacy and outcome do not differ compared to AChR-MCs

MuSK-antibodies are associated with worse outcome in myasthenic crisis requiring mechanical ventilation

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Muscle-specific kinase-antibodies (MuSK-ABs) are detected in ~ 6% of MG, but data on outcome of MuSK-MCs are still lacking. We made a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody positive MG (AchR-MG) or MuSK-MG between 2006 and 2015 in a retrospective German multicenter study. We identified 19 MuSK-AB associated MCs in 15 patients and 161 MCs in 144 patients with AchR-ABs only. In contrast to patients with AchR-AB, MuSK-AB patients were more often female (p = 0.05, OR = 2.74) and classified as Myasthenia Gravis Foundation of America-class IV before crisis (p = 0.04, OR = 3.25). MuSK-AB patients suffer more often from multiple chronic disease (p = 0.016, OR = 4.87) and were treated more invasively in terms of plasma exchanging therapies (not significant). The number of days of mechanical ventilation (MV) (43.0 ± 53.1 vs. 17.4 ± 18; p < 0.0001), days on an intensive care unit (ICU) (45.3 ± 49.5 vs. 21.2 ± 19.7; p < 0.0001), and hospital-length of stay (LOS) (55.9 ± 47.6 vs. 28.8 ± 20.9 days; p < 0.0001) were significantly increased in MuSK-MC. Remarkable is that these changes were mainly due to patients with MusK-ABs only, whereas patients’ outcome with both antibodies was similar to AchR-MCs. Furthermore, our data showed a shortened duration of MV after treatment with plasma exchanging therapies compared to treatment with intravenous immunoglobulin in MuSK-MCs. We conclude that MuSK-AB-status is associated with a longer need of MV, ICU-LOS, and hospital-LOS in MC, and therefore recommend early initiation of a disease-specific therapy

Impact of postoperative necrotizing enterocolitis after neonatal cardiac surgery on neurodevelopmental outcome at 1 year of age

ObjectivesWe analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age.MethodsUsing data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III).ResultsThe included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p &lt; 0.05; 49 with vs. 32 days without NEC, p &lt; 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [β = −11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [β = −2.8 (SE 1.3), p = 0.030] and lower MCS [β = −3.20 (SE 1.3), p = 0.016].ConclusionsPostoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome. Clinical Trial RegistrationClinicalTrials.gov identifier: NCT05996211

The impact of levodopa on non-declarative and declarative learning

Die vorliegende Arbeit hat zum Ziel, das Wissen über die Bedeutung von L-Dopa für das Langzeitgedächtnis zu erweitern. Vor dem Hintergrund, dass Parkinson- Patienten unter einem nigrostriatalem Dopaminmangel leiden und Defizite im nicht-deklarativen Gedächtnis aufweisen und ins Besondere das Striatum in nicht-deklarative Gedächtnisprozesse eingebunden ist, war die Haupthypothese, dass durch die L-Dopa-Therapie nicht- deklarative Gedächtnisleistungen bei Parkinson-Patienten positiv beeinflusst werden können. Das deklarative Gedächtnis hingegen, welches eine Funktion des medialen Temporallappensystems ist und unbeeinträchtigt bei Parkinson- Patienten zu sein scheint, wird nicht beeinflusst. Diese Hypothesen wurden durch das „Wettervorhersage-Paradigma“ und zusätzlichen Tests zu Kognition an 20 Parkinson-Patienten mit und ohne L-Dopa, sowie an 20 altersentsprechenden Gesunden ohne Medikation überprüft. Begleitende Testverfahren untersuchten den Affekt vor dem Hintergrund, dass der Affekt Lernprozesse beeinflussen kann. Entgegen der angenommenen Hypothesen beobachteten wir ein intaktes nicht-deklaratives Gedächtnis bei Parkinson-Patienten ohne L-Dopa. Im Kontrast dazu zeigten Parkinson-Patienten mit 200mg L-Dopa ein eingeschränktes nicht- deklaratives Gedächtnis. Parkinson-Patienten ohne L-Dopa waren in der deklarativen Gedächtnisaufgabe schlechter als die Gesunden. Angst- und Depressionsparameter ließen sich bei den Parkinson-Patienten durch die L-Dopa- Gabe verbessern. Die vorliegende Arbeit unterstützt die Annahme einer entscheidenden Rolle von L-Dopa in Langzeitgedächtnis- und affektiven Prozessen.We aim to assess the role of levodopa in non-declarative and declarative learning. Patients with Parkinson’s disease are known to suffer from striatal dopamine depletion and to be impaired in non- declarative memory tasks. We therefore hypothesized that the intake of levodopa may improve non- declarative learning. Furthermore, as declarative memory is represented in medial temporal lobe structures, we anticipated patients with Parkinson’s disease not to be impaired in declarative tests. We studied 20 Parkinson- patients in both on and off levodopa conditions and age- matched 20 healthy controls without medication via the weather prediction task. Additionally, we assessed the affective states. Contrary to our hypotheses we observed that non- declarative memory is intact in patients with Parkinson’s disease after withdrawal of medication. In contrast, the intake of 200mg levodopa lead to an impaired performance in the non-declarative task. The result of the declarative task without levodopa was worse compared to healthy controls. Affective states improved after the intake of levodopa. We were able to confirm the essential role of levodopa within the long-term memory system and affective status

Paradigm Change? Cardiac Output Better Associates with Cerebral Perfusion than Blood Pressure in Ischemic Stroke

IntroductionIn patients with acute ischemic stroke, penumbral perfusion is maintained by collateral flow and so far is maintained by normal mean arterial pressure (MAP) levels. Since MAP is dependent on cardiac function, optimization of cardiac output might be a valuable hemodynamic goal in order to optimize cerebral perfusion (CP).MethodsCerebral perfusion was assessed by transcranial color-coded duplex and transcranial perfusion sonography in 10 patients with acute large hemispheric stroke. Time-to-peak (TTP) values of defined regions of interest (ROI) within the middle cerebral artery (MCA) territory were assessed bilaterally in addition to mean flow velocities of the MCA. Via semi-invasive advanced hemodynamic monitoring systemic hemodynamic parameters were assessed, including MAP and cardiac index (CI). Patients received sonographic follow-up after optimizing CI.ResultsTTP values of the deeply located ROIs of the non-affected as well as the affected hemisphere correlated highly significantly with CI (in affected side r = −0.827, p = 0.002; and in non-affected side r = −0.908, p &lt; 0.0001). This demonstrates dependence of CP on CI, while correlation with MAP was not detected. Neither CI nor MAP revealed significant correlation with MCA velocity

Optimizing Cardiac Out-Put to Increase Cerebral Penumbral Perfusion in Large Middle Cerebral Artery Ischemic Lesion—OPTIMAL Study

IntroductionIn unsuccessful vessel recanalization, clinical outcome of acute stroke patients depends on early improvement of penumbral perfusion. So far, mean arterial blood pressure (MAP) is the target hemodynamic parameter. However, the correlations of MAP to cardiac output (CO) and cerebral perfusion are volume state dependent. In severe subarachnoid hemorrhage, optimizing CO leads to a reduction of delayed ischemic neurological deficits and improvement of clinical outcome. This study aims to investigate the effect of standard versus advanced cardiac monitoring with optimization of CO on the clinical outcome in patients with large ischemic stroke.Methods and analysisThe OPTIMAL study is a prospective, multicenter, open, into two arms (1:1) randomized, controlled trial. Sample size estimate: sample sizes of 150 for each treatment group (300 in total) ensure an 80% power to detect a difference of 16% of a dichotomized level of functional clinical outcome at 3 months at a significance level of 0.05. Study outcomes: the primary endpoint is the functional outcome at 3 months. The secondary endpoints include functional outcome at 6 months follow-up, and complications related to hemodynamic monitoring and therapies.DiscussionThe results of this trial will provide data on the safety and efficacy of advanced hemodynamic monitoring on clinical outcome.Ethics and disseminationThe trial was approved by the leading ethics committee of Freiburg University, Germany (438/14, 2015) and the local ethics committees of the participating centers. The study is performed in accordance with the Declaration of Helsinki and the guidelines of Good Clinical Practice. It is registered in the German Clinical Trial register (DRKS; DRKS00007805). Dissemination will include submission to peer-reviewed professional journals and presentation at congresses. Hemodynamic monitoring may be altered in a specific stroke patient cohort if the study shows that advanced monitoring is safe and improves the functional outcome