Bernd Kallmünzer

Serious Cardiac Arrhythmias After Stroke Incidence, Time Course, and Predictors—A Systematic, Prospective Analysis

Background and Purpose— Patients with acute cerebrovascular events are susceptible to serious cardiac arrhythmias, but data on the time course and the determinants of their onset are scarce. Methods— The prospective Stroke-Arrhythmia-Monitoring-Database (SAMBA) assessed cardiac arrhythmias with need for urgent evaluation and treatment in 501 acute neurovascular patients during the first 72 hours after admission to a monitored stroke unit. Arrhythmias were systematically detected by structured processing of telemetric data. Time of arrhythmia onset and predisposing factors were investigated. Results— Significant cardiac arrhythmias occurred in 25.1% of all patients. Incidence was highest during the first 24 hours after admission. Serious arrhythmic tachycardia (ventricular or supraventricular >130 beats/min) was more frequent than bradycardic arrhythmia (sinus-node dysfunction, bradyarrhythmia, or atrioventricular block °II and °III). Arrhythmias were independently associated with higher age and severer neurological deficits as measured by the National Institutes of Health Stroke Scale on admission. Conclusions— The risk for significant cardiac arrhythmia after an acute cerebrovascular event is highest during the first 24 hours of care and declines with time during the first 3 days. Along with established vascular risk factors, the National Institutes of Health Stroke Scale may be considered for a stratified allocation of monitoring capabilities. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

A Structured Reading Algorithm Improves Telemetric Detection of Atrial Fibrillation After Acute Ischemic Stroke

Background and Purpose— Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Methods— Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Results— Median effective telemetry monitoring time was 75.5 hours (interquartile range 64–86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Conclusions— Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Enteric co-innervation of striated muscle fibres in human oesophagus

Abstract  Oesophageal striated muscle of several mammalian species receives dual innervation from both vagal motor fibres originating in the brain stem and enteric nerve fibres originating in myenteric ganglia. The aim of this study was to investigate this so‐called enteric co‐innervation in the human oesophagus. Histochemical and immunohistochemical methods combined with confocal laser scanning microscopy were utilized to study innervation of 14 oesophagi obtained from body donors (age range 47–95 years). In addition, the distribution of striated and smooth muscle in longitudinal and circular layers of the tunica muscularis was studied semiquantitatively. The upper half of the oesophagus was built up of both muscle types with a predominance (>50–60%) of striated muscle, whereas the lower half consisted of smooth muscle only. The majority of motor endplates was compact and ovoid. Enteric nerve fibres on ∼17% of motor endplates stained for neuronal nitric oxide synthase, vasoactive intestinal polypeptide, galanin and neuropeptide Y and were completely separated from vagal cholinergic nerve terminals. There was remarkable variability of co‐innervation rates between striated muscle bundles with some reaching almost 50%. Myenteric neurons representing the putative source of enteric co‐innervating nerve fibres, stained for all these markers, which were almost completely colocalized with NADPH‐diaphorase. Our study provides evidence for enteric co‐innervation of striated muscle in human oesophagus. From these and recent functional results in various rodent species, we suggest that this innervation component represents an integral part of an intramural reflex mechanism for local most likely inhibitory modulation of oesophageal motility.

Mild hypothermia of 34°C reduces side effects of rt-PA treatment after thromboembolic stroke in rats

BackgroundHypothermia is neuroprotective in experimental stroke and may extend the so far limited therapeutic time window for thrombolysis. Therefore, hypothermia of 34°C and its effects on delayed thrombolysis including reperfusion-associated injury were investigated in a model of thromboembolic stroke (TE).MethodsMale Wistar rats (n = 48) were subjected to TE. The following treatment groups were investigated: control group - normothermia (37°C); thrombolysis group - rt-PA 90 min after TE; hypothermia by 34°C applied 1.5 to 5 hours after TE; combination therapy- hypothermia and rt-PA. After 24 hours infarct size, brain edema and neuroscore were assessed. Protein markers for inflammation and adhesion, gelatinase activity, and blood brain barrier (BBB) disruption were determined. MRI-measurements investigated infarct evolution and blood flow parameters.ResultsThe infarct volume and brain swelling were smaller in the hypothermia group compared to the other groups (p < 0.05 to p < 0.01). Thrombolysis resulted in larger infarct and brain swelling than all others. Hypothermia in combination with thrombolysis reduced these parameters compared to thrombolysis (p < 0.05). Moreover, the neuroscore improved in the hypothermia group compared to control and thrombolysis. Animals of the combination therapy performed better than after thrombolysis alone (p < 0.05). Lower serum concentration of sICAM-1, and TIMP-1 were shown for hypothermia and combination therapy. Gelatinase activity was decreased by hypothermia in both groups.ConclusionsTherapeutic hypothermia reduced side-effects of rt-PA associated treatment and reperfusion in our model of TE.

Head and Neck Cooling Decreases Tympanic and Skin Temperature, But Significantly Increases Blood Pressure

Background and Purpose— Localized head and neck cooling might be suited to induce therapeutic hypothermia in acute brain injury such as stroke. Safety issues of head and neck cooling are undetermined and may include cardiovascular autonomic side effects that were identified in this study. Methods— Ten healthy men (age 35±13 years) underwent 120 minutes of combined head and neck cooling (Sovika, HVM Medical). Before and after onset of cooling, after 60 and 120 minutes, we determined rectal, tympanic, and forehead skin temperatures, RR intervals, systolic and diastolic blood pressures (BP), laser-Doppler skin blood flow at the index finger and cheek, and spectral powers of mainly sympathetic low-frequency (0.04–0.15 Hz) and parasympathetic high-frequency (0.15–0.5 Hz) RR interval oscillations and sympathetic low-frequency oscillations of BP. We compared values before and during cooling using analysis of variance with post hoc analysis; (significance, P<0.05). Results— Forehead skin temperature dropped by 5.5±2.2°C with cooling onset and by 12.4±3.2°C after 20 minutes. Tympanic temperature decreased by 4.7±0.7°C within 40 minutes, and rectal temperature by only 0.3±0.3°C after 120 minutes. Systolic and diastolic BP increased immediately on cooling onset and rose by 15.3±20.8 mm Hg and 16.5±13.4 mm Hg (P=0.004) after 120 minutes, whereas skin blood flow fell significantly during cooling. RR intervals and parasympathetic RR interval high-frequency powers increased with cooling onset and were significantly higher after 60 and 120 minutes than they were before cooling. Conclusions— Head and neck cooling prominently reduced tympanic temperature and thus might also induce intracerebral hypothermia; however, it did not significantly lower body core temperature. Profound skin temperature decrease induced sympathetically mediated peripheral vasoconstriction and prominent BP increases that are not offset by simultaneous parasympathetic heart rate slowing. Prominent peripheral vasoconstriction and BP increase must be considered as possibly harmful during head and neck cooling.

Temperature management in stroke - an unsolved, but important topic.

Clinical data clearly show that elevated body temperature contributes to an unfavorable outcome after ischemic and hemorrhagic stroke. Two promising therapeutic strategies arise from this observation: (1) treatment of fever aiming to sustain normothermia and (2) induced hypothermia, targeting core body temperatures below 36.5°C. A limited number of studies investigated antipyretic strategies after acute stroke and their results were rather disappointing in terms of clinical efficacy. For that reason, it remains unproven, whether sufficient fever treatment improves functional outcome. On the other hand, strong experimental evidence supports neuroprotective effects of induced hypothermia after stroke. Yet, clinical data on this topic remain preliminary and rely on a limited number of patients, mostly enrolled in nonrandomized trials. Therefore, induced hypothermia may be considered safe and feasible after ischemic stroke, but little can be said regarding efficacy. This review summarizes the data, both on fever treatment and induced hypothermia following stroke, starting with a synopsis of the most important experimental investigations, leading to the latest clinical trials. Given the promising data and the lack of successful acute neuroprotective therapies available thus far, suggestions are given for future investigation on both topics.

Suppression of dendritic cell functions contributes to the anti-inflammatory action of granulocyte-colony stimulating factor in experimental stroke

Cerebral ischemia provokes an inflammatory cascade, which is assumed to secondarily worsen ischemic tissue damage. Linking adaptive and innate immunity dendritic cells (DCs) are key regulators of the immune system. The hematopoietic factor G-CSF is able to modulate DC-mediated immune processes. Although G-CSF is under investigation for the treatment of stroke, only limited information exists about its effects on stroke-induced inflammation. Therefore, we investigated the impact of G-CSF on cerebral DC migration and maturation as well as on the mediated immune response in an experimental stroke model in rats by means of transient middle cerebral artery occlusion (tMCAO). Immunohistochemistry and quantitative PCR were performed of the ischemic brain and flow cytometrical analysis of peripheral blood. G-CSF led to a reduction of the infarct size and an improved neurological outcome. Immunohistochemistry confirmed a reduced migration of DCs and mature antigen-presenting cells after G-CSF treatment. Compared to the untreated tMCAO group, G-CSF led to an inhibited DC activation and maturation. This was shown by a significantly decreased cerebral transcription of TLR2 and the DC maturation markers, CD83 and CD86, as well as by an inhibition of stroke-induced increase in immunocompetent DCs (OX62⁺OX6⁺) in peripheral blood. Cerebral expression of the proinflammatory cytokine TNF-α was reduced, indicating an attenuation of cerebral inflammation. Our data suggest an induction of DC migration and maturation under ischemic conditions and identify DCs as a potential target to modulate postischemic cerebral inflammation. Suppression of both enhanced DC migration and maturation might contribute to the neuroprotective action of G-CSF in experimental stroke.

Local Head and Neck Cooling Leads to Hypothermia in Healthy Volunteers

Background: Prehospital cooling of acute stroke patients would be ideal when associated with minor or no side effects. Therefore, we evaluated a cooling cap for the surface of head and cervical regions in awake volunteers. Methods: 10 healthy volunteers were treated by external cooling for 190 min using a gel-based cooling device. Vital signs, rectal temperature, tympanic temperature, the extent of shivering and individual perception of frostiness and discomfort were measured. Results: All participants (median age 35 years) successfully completed the treatment and experienced only mild to moderate discomfort. No serious adverse events and no shivering were noticed. There was a significant drop in the tympanic temperature to 34.68°C (difference from baseline: 1.7°C, 95% CI: 0.61–2.7°C, p = 0.001), in the rectal temperature to 36.65°C (difference from baseline: 0.65°C, 95% CI: 0.06–1.2°C, p = 0.019) and in the heart rate (difference from baseline: 15 beats/min, 95% CI: 0.63–30 beats/min, p = 0.035). Conclusion: Treatment with the cooling device was well tolerated by all participants. The technique had measurable effects on core body temperature (rectal) and tympanic temperature (may reflect temperature at the external ear and skin rather than intracranial). It can be considered as a simple therapeutic approach to patients with suspected stroke in the prehospital setting.

Standardized antipyretic treatment in stroke: a pilot study.

Background: Fever after acute cerebral injury is associated with unfavorable functional outcome and increased mortality, but there is controversy about the optimal antipyretic treatment. This study investigated an institutional standard operating procedure (SOP) for fever treatment in stroke patients including a sequence of pharmacologic and physical interventions. Methods: A 4-step antipyretic SOP was established for patients with acute cerebral ischemia or hemorrhage and a body temperature ≧37.5°C within the first 6 days after admission. Data on the course of body temperature, duration of fever and achievement of normothermia were recorded. Results were compared to a historic control group that underwent conventional treatment. Results: A total of 77 patients (mean age 70.4 ± 14.2 yeas) received 331 antipyretic interventions. Sequential administration of paracetamol (n = 219), metamizole (n = 71) and calf packing (n = 24) resulted in a significant drop in body temperature after 60 min in each instance. In 5 of 9 cases which were refractory to previous attempts, normothermia followed the infusion of ice-cooled saline. In more than 90% of cases treated per protocol, normothermia was achieved within 120 min. Compared to conventional treatment, fever burden was significantly lower within the first 4 days after admission (p < 0.001). Conclusion: This SOP may help to optimize antipyretic treatment for stroke patients.

Lost memories can break your heart: a case report of transient global amnesia followed by takotsubo cardiomyopathy

Takotsubo cardiomyopathy (TC), also called apical ballooning syndrome, is characterized by an acute, transient systolic dysfunction of the apical and mid segments of the left ventricle. Recently, there have been reports showing an association with neurologic disorders including myasthenic crisis [1], Guillain–Barre–Strohl syndrome [2], seizures [3] and ischemic stroke [4]. In this article, we present the case of a woman, who suffered from a second episode of transient global amnesia (TGA) followed by TC. A 62-year-old woman presented to our emergency room with typical symptoms of TGA, thereby asking repetitive questions regarding the situation and events over the last hours. Symptom onset had occurred during the visit to a public swimming pool. Apart from isolated global amnesia, the neurologic examination was normal; a CT-scan of the brain was unremarkable. An EEG was done and ruled out an epileptic cause of the syndrome. Extracranial and transcranial vascular ultrasound did not reveal any pathologic findings. The patient had a past medical history of hypothyroidism with need for oral substitution and a previous episode of TGA 2 years before. Four hours after the patient was admitted to our intermediate care unit, she developed acute chest pain and dyspnoea. The troponin I level was elevated at 4.64 ng/ml. Acute coronary syndrome was suspected and an emergency coronary angiography was performed, which did not show relevant coronary artery disease. Ventriculography revealed severe hypokinesis of mid and apical segments of the left ventricle with the characteristic shape of takotsubo cardiomyopathy (Figs. 1, 2; supplemental ultrasound video Movie—TakoTsubo.mpg). The patient was stable during the further course and showed full recovery from all amnestic deficits within 18 h. On follow-up echocardiography, a complete normalization of cardiac function with normal left ventricular diameter, no wall motion abnormalities and a normal ejection fraction were found. The patient was then discharged in a good state of health. Transient global amnesia was first described in 1956 by Guyotat and Courjon as an acute cognitive disorder with predominantly anterograde amnesia for up to 24 h [5]. Most episodes occur at the age of 50–80 years, do not show an association with vascular risk factors and are frequently precipitated by emotional stress, physical effort, water Electronic supplementary material The online version of this article (doi:10.1007/s00392-013-0590-1) contains supplementary material, which is available to authorized users.