Letter by Scheitz et al regarding article, "Randomized controlled trial of early versus delayed statin therapy in patients with acute ischemic stroke: ASSORT trial (administration of statin on acute ischemic stroke patient)"

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Tension Pneumocephalus with Diplegia and Deterioration of Consciousness

Tension pneumocephalus results from intracranial air under pressure as a rare complication after head injury or craniofacial surgery. A 58-year-old man underwent ethmoid sinus surgery and subsequently developed rapidly progressive global headache, restlessness, diplegia with sensory loss, and deterioration of the conscious level. A head CT demonstrated extensive pneumocephalus with gross compression of the brain. The frontal retention of air caused widening of the interhemispheric fissure leading to a peaked appearance of the frontal poles, referred to as the ‘Mount Fuji sign’. Surgical revision of a dural air leak resulted in rapid improvement and full clinical resolution. Early diagnosis of tension pneumocephalus and emergent surgical treatment are crucial to prevent life-threatening deterioration

Pre-hospital Triage of Acute Ischemic Stroke Patients—Importance of Considering More Than Two Transport Options

Background: Patients with acute ischemic stroke (AIS) and large vessel occlusion benefit from rapid access to mechanical thrombectomy in addition to intravenous thrombolysis. Prehospital triage algorithms to determine the optimal transport destination for AIS patients with unknown vessel status have so far only considered two alternatives: the nearest comprehensive (CSC) and the nearest primary stroke center (PSC). Objective: This study explores the importance of considering a larger number of PSCs during pre-hospital triage of AIS patients. Methods: Analysis was performed in random two-dimensional abstract geographic stroke care infrastructure environments and two models based on real-world geographic scenarios. Transport times to CSCs and PSCs were calculated to define sub-regions with specific triage properties. Possible transport destinations included the nearest CSC, the nearest PSC, and any of the remaining PSCs that are not closest to the scene, but transport to which would imply a shorter total time-to-CSC-via-PSC. Results: In abstract geographic environments, themedian relative size of the sub-region where a triage decision is required ranged from 34 to 92%. The median relative size of the sub-region where more than two triage options need to be considered ranged from 0 to 56%. The achievable reduction in time-to-thrombectomy (“benefit”) exceeded the increase in time-to-thrombolysis (“harm”) by a factor of 2 in 30.5–37.0%of the sub-region where more than two triage options need to be considered. Results were confirmed in geographic environments based on real-world urban and rural stroke care infrastructures. Conclusion: Pre-hospital triage algorithms for AIS patients that only take into account the nearest CSC and the nearest PSC as transport destinations may be unable to identify the optimal transport destination for a significant proportion of patients

Pre-hospital Triage of Acute Ischemic Stroke Patients—Importance of Considering More Than Two Transport Options

Background: Patients with acute ischemic stroke (AIS) and large vessel occlusion benefit from rapid access to mechanical thrombectomy in addition to intravenous thrombolysis. Prehospital triage algorithms to determine the optimal transport destination for AIS patients with unknown vessel status have so far only considered two alternatives: the nearest comprehensive (CSC) and the nearest primary stroke center (PSC).Objective: This study explores the importance of considering a larger number of PSCs during pre-hospital triage of AIS patients.Methods: Analysis was performed in random two-dimensional abstract geographic stroke care infrastructure environments and two models based on real-world geographic scenarios. Transport times to CSCs and PSCs were calculated to define sub-regions with specific triage properties. Possible transport destinations included the nearest CSC, the nearest PSC, and any of the remaining PSCs that are not closest to the scene, but transport to which would imply a shorter total time-to-CSC-via-PSC.Results: In abstract geographic environments, the median relative size of the sub-region where a triage decision is required ranged from 34 to 92%. The median relative size of the sub-region where more than two triage options need to be considered ranged from 0 to 56%. The achievable reduction in time-to-thrombectomy (“benefit”) exceeded the increase in time-to-thrombolysis (“harm”) by a factor of 2 in 30.5–37.0% of the sub-region where more than two triage options need to be considered. Results were confirmed in geographic environments based on real-world urban and rural stroke care infrastructures.Conclusion: Pre-hospital triage algorithms for AIS patients that only take into account the nearest CSC and the nearest PSC as transport destinations may be unable to identify the optimal transport destination for a significant proportion of patients

A Neurological Outpatient Clinic for Patients With Post-COVID-19 Syndrome — A Report on the Clinical Presentations of the First 100 Patients

Background and Objectives: Neurological and psychiatric symptoms are frequent in patients with post-COVID-19 syndrome (PCS). Here, we report on the clinical presentation of the first 100 patients who presented to our PCS Neurology outpatient clinic ≥ 12 weeks after the acute infection with SARS-CoV-2. To date, PCS is only defined by temporal connection to SARS-CoV-2 infection. Identification of clinical phenotypes and subgroups of PCS is urgently needed. Design: We assessed clinical data of our first 100 ambulatory patients regarding clinical presentations; self-questionnaires focusing on daytime sleepiness, mood, and fatigue; and a screening assessment for detecting cognitive impairment. Results: A total of 89% of the patients presenting to the Neurology outpatient clinic had an initially mild course of COVID-19 and had not been hospitalized. The majority of the patients were female (67 vs. 33% male). The most frequent symptom reported was cognitive impairment (72%). There were 30% of patients who reported cognitive deficits and scored below 26 points on the Montreal Cognitive Assessment Scale. Fatigue (67%), headache (36%), and persisting hyposmia (36%) were also frequently reported; 5.5% of all patients showed signs of severe depression. Discussion: To our knowledge, this is the first report of patient data of a PCS Neurology outpatient clinic. Neurological sequelae also exist for more than 3 months after mainly mild SARS-CoV-2 acute infections. The reported symptoms are in accordance with recently published data of hospitalized patients

Smoking Does Not Alter Treatment Effect of Intravenous Thrombolysis in Mild to Moderate Acute Ischemic Stroke—A Dutch String-of-Pearls Institute (PSI) Stroke Study

Background:The smoking-thrombolysis paradox refers to a better outcome in smokers who suffer from acute ischemic stroke (AIS) following treatment with thrombolysis. However, studies on this subject have yielded contradictory results and an interaction analysis of exposure to smoking and thrombolysis in a large, multicenter database is lacking. Methods:Consecutive AIS patients admitted within 12 h of symptom onset between 2009 and 2014 from the prospective, multicenter stroke registry (Dutch String-of-Pearls Stroke Study) were included for this analysis. We performed a generalized linear model for functional outcome 3 months post-stroke depending on risk of the exposure variables (smoking yes/no, thrombolysis yes/no). The following confounders were adjusted for: age, smoking, hypertension, atrial fibrillation, diabetes mellitus, stroke severity, and stroke etiology. Results:Out of 468 patients, 30.6% (N= 143) were smokers and median baseline NIHSS was 3 (interquartile range 1-6). Smoking alone had a crude and adjusted relative risk (RR) of 0.99 (95% CI 0.89-1.10) and 0.96 (95% CI 0.86-1.01) for good outcome (modified Rankin Score <= 2), respectively. A combination of exposure variables (smoking and thrombolysis) did not change the results significantly [crude RR 0.87 (95% CI 0.74-1.03], adjusted RR 1.1 (95%CI 0.90-1.30)]. Smoking alone had an adjusted RR of 1.2 (95% CI 0.6-2.7) for recanalization following thrombolysis (N= 88). Conclusions:In patients with mild to moderate AIS admitted within 12 h of symptom onset, smoking did not modify treatment effect of thrombolysis

Frequency and phenotype of thalamic aphasia

Background: Aphasia is a recognized presenting symptom of thalamic lesions. Little is known regarding its frequency and phenotype. We examined the frequency of thalamic aphasia following Isolated Acute unilateral ischemic Lesions in the Thalamus (IALT) with respect to lesion location. Furthermore, we characterized thalamic aphasia according to affected language domains and severity. Methods: Fifty-two patients with IALT were analyzed [44% female, median age: 73 years (IQR: 60-79)]. Lesion location was determined using 3-Tesla magnetic resonance imaging and categorized as anterior, posterior, paramedian or inferolateral. Standardized language assessment was performed using the validated Aphasia checklist (ACL) directly after symptom onset. Aphasia was defined as an ACL sum score of < 135 (range: 0-148). Results: Of 52 patients, 23 (44%) fulfilled the ACL diagnostic criteria for aphasia, including nearly all lesion locations and both sides. The average ACL sum score was 132 +/- 11 (range: 98-147). Aphasia was characterized by deficits within domains of complex understanding of speech and verbal fluency. Patients with left anterior IALT were most severely affected, having significantly lower ACL scores than all other patients (117 +/- 13 vs. 135 +/- 8; p < 0.001). In particular, aphasia in patients with left anterior IALT was characterized by significantly worse performance in the rating of verbal communication, verbal fluency, and naming (all p <= 0.001). Conclusion: Aphasia occurs in almost half of patients with focal thalamic lesions. Thalamic aphasia is not confined to one predefined thalamic lesion location, but language deficits are particularly pronounced in patients with left anterior IALT presenting with a distinct pattern

Induced pluripotent stem cell-derived brain organoids as potential human model system for chemotherapy induced CNS toxicity

Neurotoxic phenomena are among the most common side effects of cytotoxic agents. The development of chemotherapy-induced polyneuropathy (CIPN) is a well-recognized adverse reaction in the peripheral nervous system, while changes of cognitive functions (post-chemotherapy cognitive impairment (PCCI)) are more diffuse and have only recently drawn scientific interest. PCCI in patients most often displays as short-term memory loss, reduced multitasking ability or deficits in language. Not least, due to a lack of preclinical human model systems, the underlying molecular mechanisms are poorly understood, and treatments are missing. We thus investigated whether induced pluripotent stem cell (iPSC)-derived brain organoids can serve as a human model system for the study of chemotherapy induced central nervous system toxicity. We robustly generated mature brain organoids from iPSC-derived neuronal precursor cells (NPC), which showed a typical composition with 1) dividing NPCs forming ventricle like structures 2) matured neurons and 3) supporting glial cells closer to the surface. Furthermore, upon stimulation the brain organoids showed functional signaling. When exposed to increasing concentrations of paclitaxel, a frequently used chemotherapy drug, we observed time dependent neurotoxicity with an EC50 of 153 nM, comparable to a published murine model system. Histological analysis after paclitaxel exposure demonstrated dose dependent apoptosis induction and reduced proliferation in the organoids with further Western blot analyses indicating the degradation of neuronal calcium sensor one protein (NCS-1) and activation of Caspase-3. We could also provide evidence that paclitaxel treatment negatively affects the pool of neuronal and astrocyte precursor cells as well as mature neurons. In summary our data suggests that human iPSC derived brain organoids are a promising preclinical model system to investigate molecular mechanisms underlying PCCI and to develop novel prevention and treatment strategies.Peer Reviewe

Neurological update: use of cardiac troponin in patients with stroke

Cardiac troponin is a specific and sensitive biomarker to identify and quantify myocardial injury. Myocardial injury is frequently detected after acute ischemic stroke and strongly associated with unfavorable outcomes. Concomitant acute coronary syndrome is only one of several possible differential diagnoses that may cause elevation of cardiac troponin after stroke. As a result, there are uncertainties regarding the correct interpretation and optimal management of stroke patients with myocardial injury in clinical practice. Elevation of cardiac troponin may occur as part of a ‘Stroke-Heart Syndrome’. The term ‘Stroke-Heart Syndrome’ subsumes a clinical spectrum of cardiac complications after stroke including cardiac injury, dysfunction, and arrhythmia which may relate to disturbances of autonomic function and the brain–heart axis. In this review, we provide an up-to-date overview about prognostic implications, mechanisms, and management of elevated cardiac troponin levels in patients with acute ischemic stroke

Body temperature measurement in mice during acute illness: implantable temperature transponder versus surface infrared thermometry

Body temperature is a valuable parameter in determining the wellbeing of laboratory animals. However, using body temperature to refine humane endpoints during acute illness generally lacks comprehensiveness and exposes to inter-observer bias. Here we compared two methods to assess body temperature in mice, namely implanted radio frequency identification (RFID) temperature transponders (method 1) to non-contact infrared thermometry (method 2) in 435 mice for up to 7 days during normothermia and lipopolysaccharide (LPS) endotoxin-induced hypothermia. There was excellent agreement between core and surface temperature as determined by method 1 and 2, respectively, whereas the intra-and inter-subject variation was higher for method 2. Nevertheless, using machine learning algorithms to determine temperature-based endpoints both methods had excellent accuracy in predicting death as an outcome event. Therefore, less expensive and cumbersome non-contact infrared thermometry can serve as a reliable alternative for implantable transponder-based systems for hypothermic responses, although requiring standardization between experimenters