Hermann Neugebauer

DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS): a protocol of a multicenter randomized controlled clinical trial and a literature review.

Rationale Although decompressive hemicraniectomy clearly reduces mortality in severe space-occupying middle cerebral artery infarction (so-called malignant middle cerebral artery infarction), every fifth patient still dies in the acute phase and every third patient is left with moderate to severe disability. Therapeutic hypothermia is a neuroprotective and antiedematous treatment option that has shown promising effects in severe stroke. A combination of both treatment strategies may have the potential to further reduce mortality and morbidity in malignant middle cerebral artery infarction, but needs evaluation of its efficacy within the setting of a randomized clinical trial. Aims The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke (DEPTH-SOS) trial aims to investigate safety and feasibility of moderate therapeutic hypothermia (33°C ± 1) over at least 72 h in addition to early decompressive hemicraniectomy (≤48 hours after symptom onset) in patients with malignant middle cerebral artery infarction. Design The DEcompressive surgery Plus hypoTHermia for Space-Occupying Stroke is a prospective, multicenter, open, two-arm (1:1) comparative, randomized, controlled trial. Study outcomes The primary end-point is mortality at day 14. The secondary end-points include functional outcome at day 14 and at 12 months follow-up, and complications related to hypothermia. Discussion The results of this trial will provide data on safety and feasibility of moderate hypothermia in addition to decompressive hemicraniectomy in malignant middle cerebral artery infarction. Furthermore, efficacy data on early mortality and long-term functional outcome will be obtained, forming the basis of subsequent trials.

Hemicraniectomy for Malignant Middle Cerebral Artery Infarction: Current Status and Future Directions

Malignant middle cerebral artery infarction is a life-threatening sub-type of ischemic stroke that may only be survived at the expense of permanent disability. Decompressive hemicraniectomy is an effective surgical therapy to reduce mortality and improve functional outcome without promoting most severe disability. Evidence derives from three European randomized controlled trials in patients up to 60 years. The recently finished DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY – II trial gives now high-level evidence for the effectiveness of decompressive hemicraniectomy in patients older than 60 years. Nevertheless, pressing issues persist that need to be answered in future clinical trials, e.g. the acceptable degree of disability in survivors of malignant middle cerebral artery infarction, the importance of aphasia, and the best timing for decompressive hemicraniectomy. This review provides an overview of the current diagnosis and treatment of malignant middle cerebral artery infarction with a focus on decompressive hemicraniectomy and outlines future perspectives.

Space-occupying cerebellar infarction: complications, treatment, and outcome

Space-occupying brain edema is a frequent and one of the most dreaded complications in ischemic cerebellar stroke. Because the tight posterior fossa provides little compensating space, any space-occupying lesion can lead to life-threatening complications through brainstem compression or compression of the fourth ventricle and subsequent hydrocephalus, both of which may portend transtentorial/transforaminal herniation. Patients with large cerebellar infarcts should be treated and monitored very early on in an experienced stroke unit or (neuro)intensive care unit. The general treatment of ischemic cerebellar infarction does not differ from that of supratentorial ischemic strokes. Treatment strategies for space-occupying edema include pharmacological antiedema and intracranial pressure-lowering therapies, ventricular drainage by means of an extraventricular drain, and suboccipital decompressive surgery, with or without resection of necrotic tissue. Timely escalation of treatment is crucial and should be guided by clinical and neuroradiological rationales. Patients in a coma after hydrocephalus and/or local brainstem compression may also benefit from more aggressive surgical treatment, as long as the conditions are reversible. Contrary to the general belief that outcome in survivors of space-occupying cerebellar stroke is usually good, recent studies suggest that for many of these patients, the long-term outcome is not good. In particular, advanced age and additional brainstem infarction seem to be predictors for poor outcome. Further trials are necessary to investigate these findings systematically and provide better selection criteria to help guide decisions about surgical therapies, which should always be carried out in close cooperation among neurointensive care physicians, neurologists, and neurosurgeons.

DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY - Registry (DESTINY-R): design and protocols

BackgroundRandomized controlled trials (RCT) on the treatment of severe space-occupying infarction of the middle cerebral artery (malignant MCA infarction) showed that early decompressive hemicraniectomy (DHC) is life saving and improves outcome without promoting most severe disablity in patients aged 18–60 years. It is, however, unknown whether the results obtained in the randomized trials are reproducible in a broader population in and apart from an academical setting and whether hemicraniectomy has been implemented in clinical practice as recommended by national and international guidelines. In addition, they were not powered to answer further relevant questions, e.g. concerning the selection of patients eligible for and the timing of hemicraniectomy. Other important issues such as the acceptance of disability following hemicraniectomy, the existence of specific prognostic factors, the value of conservative therapeutic measures, and the overall complication rate related to hemicraniectomy have not been sufficiently studied yet.Methods/DesignDESTINY-R is a prospective, multicenter, open, controlled registry including a 12 months follow-up. The only inclusion criteria is unilateral ischemic MCA stroke affecting more than 50% of the MCA-territory. The primary study hypothesis is to confirm the results of the RCT (76% mRS ≤ 4 after 12 months) in the subgroup of patients additionally fulfilling the inclusion cirteria of the RCT in daily routine. Assuming a calculated proportion of 0.76 for successes and a sample size of 300 for this subgroup, the width of the 95% CI, calculated using Wilsons method, will be 0.096 with the lower bound 0.709 and the upper bound 0.805.DiscussionThe results of this study will provide information about the effectiveness of DHC in malignant MCA infarction in a broad population and a real-life situation in addition to and beyond RCT. Further prospectively obtained data will give crucial information on open questions and will be helpful in the plannig of upcomming treatment studies.Trial registration(ICTRP and DRKS): DRKS00000624

Association of prothrombin complex concentrate administration and hematoma enlargement in non–vitamin K antagonist oral anticoagulant–related intracerebral hemorrhage

To investigate parameters associated with hematoma enlargement in non–vitamin K antagonist oral anticoagulant (NOAC)‐related intracerebral hemorrhage (ICH).

Pathological laughing and crying in amyotrophic lateral sclerosis is related to frontal cortex function

The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-defined which kind of stimuli—contextually appropriate or inappropriate—elicit episodes of PLC, and if the phenomenon is a result of a lack of inhibition from the frontal cortex (“top-down-theory”) or due to an altered processing of sensory inputs at the brainstem level (“bottom-up-theory”). To address these questions, we studied ten amyotrophic lateral sclerosis (ALS) patients with PLC and ten controls matched for age, sex and education. Subjects were simultaneously exposed to either emotionally congruent or incongruent visual and auditory stimuli and were asked to rate pictures according to their emotional quality. Changes in physiological parameters (heart rate, galvanic skin response, activity of facial muscles) were recorded, and a standardized self-assessment lability score (CNS-LS) was determined. Patients were influenced in their rating behaviour in a negative direction by mood-incongruent music. Compared to controls, they were influenced by negative stimuli, i.e. they rated neutral pictures more negatively when listening to sad music. Patients rated significantly higher on the CNS-LS. In patients, changes of electromyographic activity of mimic muscles during different emotion-eliciting conditions were explained by frontal cortex dysfunction. We conclude that PLC is associated with altered emotional suggestibility and that it is preferentially elicited by mood-incongruent stimuli. In addition, physiological reactions as well as behavioural changes suggest that this phenomenon is primarily an expression of reduced inhibitory activity of the frontal cortex, since frontal dysfunction could explain changes in physiological parameters in the patient group. We consider these findings being important for the clinical interpretation of emotional reactions of ALS patients.

Perihematomal Diffusion Restriction in Intracerebral Hemorrhage Depends on Hematoma Volume, But Does Not Predict Outcome

Background: Perihematomal diffusion restriction (PDR) is a frequent finding in primary intracerebral hemorrhage (ICH) on diffusion-weighted MRI. Its frequency, associated clinical and imaging findings and impact on clinical outcome are not well understood. Methods: This is a retrospective single-center analysis of 172 patients with primary ICH who received MRI within 24 h from symptom onset. PDR was defined as a reduction of apparent diffusion coefficient below 550 × 10-6 mm2/s. Multivariate regression analyses were used to assess independent imaging and clinical predictors of PDR. Clinical outcome was assessed using the modified Rankin scale (mRS) at discharge. Results: PDR was present in 88 patients (51.2%). Median PDR volume was 1.1 ml (interquartile range 0.2-4.2). Multivariate analyses identified hematoma volume as the key independent predictor of PDR. The volume of perihematomal edema, lobar hematoma location and low diastolic blood pressure at admission were further predictors. Although the occurrence of PDR correlated with in-hospital mortality (75.0 vs. 43.4%, p < 0.001) and moderately severe to severe disability or death at discharge (mRS ≥4; 56.4 vs. 27.8%, p = 0.002), PDR was not an independent predictor of clinical outcome. In contrast, hematoma volume, ventricular extension of hemorrhage and higher age independently predicted an adverse clinical outcome. Conclusions: PDR is common after primary ICH within 24 h of symptom onset. Hematoma volume was identified as the key predictor of PDR. Although PDR was associated with mortality and severe disability, this effect was confounded by established risk factors. These results do not support a role of early PDR as prognostic factor after ICH independent of hematoma volume.

Large Size Hemicraniectomy Reduces Early Herniation in Malignant Middle Cerebral Artery Infarction

Background: Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in-hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in-hospital mortality in patients suffering from MMI. Methods: We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation. Results: In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment. Conclusion: Despite a more aggressive surgical approach, eDHC may reduce early in-hospital mortality and limit transtentorial herniation. Prospective studies are warranted to confirm our results and assess general safety of eDHC.

Attitudes of Nurses Toward Disability and Treatment in Space-Occupying Middle Cerebral Artery Stroke

BackgroundAttitudes toward the degree of acceptable disability and the importance of aphasia are critical in deciding on decompressive hemicraniectomy (DHC) in space-occupying middle cerebral artery stroke (SOS). The attitudes of nurses deserve strong attention, because of their close interaction with patients during acute stroke treatment.MethodsThis is a multicenter survey among 627 nurses from 132 hospitals in Germany. Questions address the acceptance of disability, importance of aphasia, and the preferred treatment in the hypothetical case of SOS.ResultsModified Rankin Scale (mRS) scores of 1 and 2 were considered acceptable by the majority of all respondents (89.7%). A mRS of 3, 4, and 5 was considered acceptable by 60.0, 15.5, and 1.6%, respectively. DHC was indicated as the treatment of choice in 31.4%. Every third participant considered the presence of aphasia important for treatment decision (33.3%). Older respondents more often refrained from DHC, irrespective of the presence of aphasia (dominant hemisphere p = 0.001, non-dominant hemisphere p = 0.004). Differences regarding acceptable disability and treatment decision were dependent on age, sex, and having relatives with stroke.ConclusionMost German nurses indicate moderately severe disability after SOS not to be acceptable, without emphasizing the presence of aphasia. The results call for greater scientific efforts in order to find reliable predictors for outcome after SOS.

Decompressive craniectomy in malignant middle cerebral artery infarction To be, or not to be?

Complete or subtotal infarction in the territory of the middle cerebral artery (MCA) may be complicated by the formation of a space-occupying cerebral edema, which leads to fatal transtentorial herniation within a few days. Even maximum conservative treatment may not change the course of the disease substantially. These so-called malignant MCA infarctions (MMI) are, therefore, life-threatening events and survivors have permanent disability.1