Karsten Schwerdtfeger

European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

Background Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. Method A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9–12, and avoidance of corticosteroids. Conclusion These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome.

Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Epidemiology and prevention of fatal head injuries in Germany – trends and the impact of the reunification

SummaryA review of the data published on the epidemiology of traumatic brain injuries (TBI) reveals that the data of almost all studies are drawn from local or regional series. Nationwide data are rarely available, or are extrapolated from regional data. In Germany, there has been a nationwide mortality register with ICD-9-coded diagnoses since 1968. In addition, it has been compulsory since 1994 that all hospitals in Germany provide ICD-9 data on all admissions and discharges.Based on data provided by the Federal Bureau of Statistics (Statistisches Bundesamt) in Wiesbaden, all head injuries between 1972 and 1998 were analyzed according to ICD-9 and after 1998 according to the updated ICD-10. The data of hospitalized cases and fatal cases were correlated with population data to calculate incidences and mortality rates. Age-group specific data were also available and analyzed.Head injuries in Germany accounted in 1998 for 19.59% of all injuries. The incidence is 337/100,000. The incidence rate of serious head injury is 33.5/100,000. Mortality decreased continuously from 27.2/100,000 in 1972 to 9.0/100,000 in 2000. The mortality is highest in the group older than 75 years. 68.4% of persons with head injury die before admission to a hospital.After the reunification in 1989/1990, the number of fatal head injuries showed a temporary increase. The number of patients treated in-hospital remained essentially unchanged (276/564 patients in 1998). The majority of hospitalized patients suffered minor head injury.Conclusion: Analysis of the admission/discharge data of all German hospitals reveals surprising inside views of age group-related incidence and mortality rates of head injuries in this country. Future research should be focused on patients with minor head injuries who account for nearly 200,000 cases of in-hospital treatment.

Patterns of relapse and late toxicity after resection and whole-brain radiotherapy for solitary brain metastases

BackgroundThis retrospective analysis was performed in order to evaluate the pattern of relapse and the risk of late toxicity for solitary brain metastases treated with surgery and whole-brain radiotherapy and to correlate the results with those from radiosurgical trials.Patients and MethodsFrom a total of 66 patients, 52 received 10×3 Gy and 10 were treated with 20×2 Gy whole-brain radiotherapy after resection of their brain metastases.ResultsThe actuarial probability of relapse was 27% and 55% after 1 and 2 year(s), respectively. The local relapse rate (at the original site of resected brain metastases) was rather high for melanoma, non-breast adenocarcinoma, and squamous-cell carcinoma. No local relapse occurred in breast cancer and small-cell carcinoma. Failure elsewhere in the brain seemed to be influenced by extracranial disease activity. Size of brain metastases and total dose showed no correlation with relapse rate. Occurrence of brain relapse was not associated with a reduced survival time, because 10/15 patients who developed a relapse received salvage therapy. Of the patients, 11 had symptoms of late radiation toxicity (the actuarial probability was 42% after 2 years).ConclusionsMost results of surgical and radiosurgical studies are comparable to ours. Several randomized trials investigate surgical resection versus radiosurgery, as well as the effects of additional whole-brain radiotherapy in order to define the treatment of choice. Some data support the adjuvant application of 10×3 Gy over 2 weeks as a reasonable compromise when local control, toxicity, and treatment time have to be considered.ZusammenfassungHintergrundDas Rezidivmuster und die chronischen Strahlenspätfolgen nach Therapie solitärer Hirnmetastasen wurden retrospektiv ausgewertet. Die Behandlung bestand in einer Metastasenresektion und einer adjuvanten Ganzhirnbestrahlung. Die Ergebnisse wurden mit denen der Radiochirurgie verglichen.Patientengut und MethodeNach der Resektion der Hirnmetastase erhielten 52 von 66 Patienten eine Ganzhirnbestrahlung mit zehn Fraktionen von 3 Gy in zwei Wochen und zehn eine solche mit 20 Fraktionen von 2 Gy in vier Wochen.ErgebnisseDie Kaplan-Meier-Analyse ergab eine, Rezidivrate von insgesamt 27% nach einem bzw. 55% nach zwei Jahren. Rezidive im Bereich der resezierten Metastase wurden am häufigsten bei Melanomen, Adenokarzinomen (mit Ausnahme der Mammakarzinome) und Plattenepithelkarzinomen beobachtet. Dagegen traten bei Mammakarzinomen und kleinzelligen Karzinomen keine solchen Rezidive auf. Das Auftreten von Hirnmetastasen anderer Lokalisation schien vom Vorhandensein unkontrollierter extrakranieller Tumormanifestationen abhängig zu sein. Die Größe der Hirnfiliae und die Gesamtreferenzdosis der Strahlentherapie korrelierten nicht mit den Rezidivraten. Die Überlebenszeit der Patienten, die ein Rezidiv erlitten, unterschied sich nicht von der der anderen, da in zehn von 15 Rezidivfällen eine Salvagetherapie möglich war. Elf Patienten entwickelten chronische Strahlenspätfolgen. Nach Kaplan-Meier-Analyse betrug das Risiko 42% nach zwei Jahren.SchlußfolgerungenDie meisten Ergebnisse operativer und radiochirurgischer Studien sind den eigenen vergleichbar. Derzeit werden beide Verfahren in randomisierten Studien, miteinander verglichen. Auch die Effekte einer zusätzlichen Ganzhirnbestrahlung werden auf diese Weise untersucht. Unter Berücksichtigung der lokalen Kontrollrate, der Nebenwirkungen und der Behandlungszeit lassen einige Literaturangaben die adjuvante Applikation von zehnmal 3 Gy in zwei Wochen als vernünftigen Kompromiß erscheinen.

Changes in Linear Dynamics of Cerebrovascular System After Severe Traumatic Brain Injury

Background and Purpose— We sought to describe the dynamic changes in the cerebrovascular system after traumatic brain injury by transfer function estimation and coherence. Methods— In 42 healthy volunteers (mean±SD age, 37±17 years; range, 17 to 65 years), spontaneous fluctuations of middle cerebral artery blood flow velocity and of finger blood pressure (BP) were simultaneously recorded over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative spectra of coherence, phase shift, and gain over the frequency range of 0 to 0.25 Hz. Similar recordings were performed in 24 patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8; mean±SD age, 50±20 years) serially on days 1, 3, 5, and 8 after trauma. Cranial perfusion pressure was kept at >70 mm Hg. Each blood flow velocity/BP recording was related to the presence or absence of middle cerebral artery territory brain parenchyma lesions on cranial CT performed within a close time frame. Results— In controls, hypocapnia decreased coherence (0.0 to 0.20 Hz), increased phase shift (0.0 to 0.17 Hz), and decreased gain in the frequency range of 0.0 to 0.11 Hz but increased gain at frequencies of 0.20 to 0.25 Hz (P <0.01 for all frequency ranges reported). In patients with traumatic brain injury, 102 investigations were possible. Compared with controls, coherence was increased in the frequency range <0.03 Hz and between 0.13 and 0.25 Hz in both normocapnia and hypocapnia, irrespective of the CT findings. Gain was unchanged in normocapnia and in the absence of a CT lesion. Gain was decreased in hypocapnia at frequencies >0.12 Hz irrespective of the presence/absence of a CT lesion. Phase shift decreased rapidly between 0.06 and 0.13 Hz under hypocapnic conditions and under normocapnic conditions in the presence of a CT lesion (P < 0.01). Conclusions— Use of spontaneous fluctuations of blood flow velocity and BP to assess the cerebrovascular system dynamically requires consideration of the Paco2 level. In different conditions, including severe traumatic brain injury, the cerebrovascular system behaves linearly only in parts of the investigated frequency range.

Alterations of norepinephrine levels in plasma and CSF of patients after traumatic brain injury in relation to disruption of the blood-brain barrier

Summary Background. In injured brain tissue with a disrupted blood-brain barrier (BBB) catecholamines such as norepinephrine (NE) are known to enhance glucose consumption and cerebral blood flow but may lead to an energy depletion increasing the risk of ischemia. Therefore it is of great interest whether the exogenous administration of NE used mainly to maintain an adequate cerebral perfusion pressure influences CSF NE levels or not, and whether elevated plasma or CSF leves of NE can influence the actual clinical condition. We addressed this issue by measuring the levels of NE in CSF and plasma and correlating them with the actual clinical condition of the patients. Methods. In 29 patients with severe TBI (<8 points on the Glasgow Coma cale, GCS) NE levels were analysed by high performance liquid chromatography (HPLC) in paired blood and CSF specimens which were collected from days 1 to 14 after severe TBI (total number of pairs=121). The integrity of the BBB was evaluated by determining the CSF/serum albumin ratio. The clinical condition of the patients was assessed by GCS. Results. Elevated plasma and CSF NE levels were observed in 50% of all samples, most consistently in patients treated with NE. NE elevation in CSF was independent of whether or not the BBB remained intact. There was no correlation between GCS and the levls of NE in CSF or plasma either in samples from the treated or the untreated group. Interpretation. Exogenous administration of NE seems to increase NE levels in plasma and CSF. However, in this group of patients with severe TBI there was no clincal evidence that exogenous administration of NE was detrimental to the traumatized patients.

Brain lesion size and phase shift as an index of cerebral autoregulation in patients with severe head injury.

Summary¶Background. Whether the phase relationship (phase shift) between cerebral blood flow velocity as assessed by transcranial Doppler ultrasound and blood pressure at 0.1 Hz can be used to assess cerebral autoregulation (CA) in patients with severe traumatic brain injury (TBI).Methods. In 33 healthy volunteers (mean age, SD; 37±17 years, range 17–65) middle cerebral artery (MCA) blood velocity (V) was recorded simultaneously with finger blood pressure (BP) over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative data. In 27 patients with severe TBI (Glasgow Coma scale score ≤8) serial close in time investigations of cranial computed tomography (CT) scanning and phase shift assessment were performed on days 1, 3, 5, and 8 after trauma. Phase shift in the MCA was compared to brain parenchyma lesion size in the MCA territory on CT scanning. Lesion size was classified into 0, normal; 1, presence of a small lesion (diameter <3 cm); 2, presence of a large lesion (>3 cm).Findings. Compared to normocapnia, hypocapnia significantly increased phase shift at 0.1 Hz from 78±28° to 101±25° (p < 0.001). In the TBI patients, 115 comparisons between CT findings and CA results were possible. Phase shift detected a pathological CA in 31 instances, which were more frequent in CT lesion type 2 (19/42) than in group 0 (7/44) and group 1 (5/29).Interpretation. When CA is intended to be assessed by use of phase shift, the hyperventilation setting needs its own reference values. In MCA territories containing a traumatic lesion greater than 3 cm in diameter phase shift at 0.1 Hz will detect a high frequency (44%) of a disturbed state of CA.

Adaptive Time-Scale Feature Extraction in Electroencephalographic Responses To Transcranial Magnetic Stimulation

Electroencephalographic responses evoked by transcranial magnetic stimulation (TMS) gain more and more interest for basic neurophysiological research and possibly diagnostic purposes. However, the separation of magnetically from non-magnetically induced brain activity still remains a challenge due to superimposed secondary effects, in particular auditory and somatosensory evoked potentials. In this study, we use optimized tight wavelet frames for the adaptive extraction of discriminant electroencephalographic time-scale features during TMS using figure-of-eight coil for focal stimulation and a combined auditory and somatosensory stimulation (ASS) paradigm. We restrict our focus to large-scale features which correspond to slow wave cortical potentials (SCPs). These potentials might reflect thalamocortical dynamics and are frequently used in biofeedback therapies. The proposed methods allows for a robust extraction of slow wave components and separated clearly the TMS from the ASS data. It is concluded that our study strongly supports recent suggestions that TMS modulates SCPs, reinforcing the theory that TMS leads to long term changes in the cortical excitability.

The Effects of Selective Brain Hypothermia and Decompressive Craniectomy on Brain Edema After Closed Head Injury in Mice

Intractable brain edema remains one of the main causes of death after traumatic brain injury (TBI). Brain hypothermia and decompressive craniectomy have been considered as potential therapies. The goal of our experimental study was to determine if selective hypothermia in combination with craniectomy could modify the development of posttraumatic brain edema. Male CD-1 mice were anesthetized with halothane and randomly assigned into the following groups: sham-operated (n = 5), closed head injury (CHI) alone (n = 5), CHI followed by craniectomy at 1 h post-TBI (n = 5) and CHI + craniectomy and selective hypothermia (focal brain cooling using cryosurgery device) maintained for 5 h (n = 5). Animals were sacrificed at 7 h posttrauma and brains were removed, sagittally dissected and dried. The brain water content of separate hemispheres was calculated from the weight difference before and after drying. In the CHI alone group there was no significant increase in brain water content in both the ipsi- and contralateral hemispheres (80.59 +/- 1% and 78.74 +/- 0.9% in the CHI group vs. 79.31 +/- 0.7% and 79.01 +/- 0.3% in the sham group, respectively). Brain edema was significantly increased ipsilaterally in the trauma + craniectomy group (82.11 +/- 0.6%, p < 0.05), but not in the trauma + craniectomy + hypothermia group (81.52 +/- 1.1%, p > 0.05) as compared to the sham group (79.31 +/- 0.7%). These data suggest that decompressive craniectomy leads to an increase in brain water content after CHI. Additional focal hypothermia may be an effective approach in the treatment of posttraumatic brain edema.

Denoising of single-trial matrix representations using 2D nonlinear diffusion filtering

In this paper we present a novel application of denoising by means of nonlinear diffusion filters (NDFs). NDFs have been successfully applied for image processing and computer vision areas, particularly in image denoising, smoothing, segmentation, and restoration. We apply two types of NDFs for the denoising of evoked responses in single-trials in a matrix form, the nonlinear isotropic and the anisotropic diffusion filters. We show that by means of NDFs we are able to denoise the evoked potentials resulting in a better extraction of physiologically relevant morphological features over the ongoing experiment. This technique offers the advantage of translation-invariance in comparison to other well-known methods, e.g., wavelet denoising based on maximally decimated filter banks, due to an adaptive diffusion feature. We compare the proposed technique with a wavelet denoising scheme that had been introduced before for evoked responses. It is concluded that NDFs represent a promising and useful approach in the denoising of event related potentials. Novel NDF applications of single-trials of auditory brain responses (ABRs) and the transcranial magnetic stimulation (TMS) evoked electroencephalographic responses denoising are presented in this paper.