The prognosis of spontaneous intracerebral hemorrhage (sICH) is poor because of the mass effect arising from the hematoma and the associated peri-hemorrhagic edema, leading to increased intracranial ...pressure. Because the efficacy of surgical and anti-edematous treatment strategies is limited, we investigated the effects of mild induced hypothermia in patients with large sICH.
Twelve patients with supratentorial sICH >25 mL were treated by hypothermia of 35 degrees C for 10 days. Evolution of hematoma volume and perifocal edema was measured by cranial CT. Functional outcome was assessed after 90 days. These patients were compared to patients (n=25; inclusion criteria: sICH volume >25 mL, no acute restriction of medical therapy on admission) from the local hemorrhage data bank (n=312). Side effects of hypothermia were analyzed.
All patients from both groups needed mechanical ventilation and were treated in a neurocritical care unit. All hypothermic patients (mean age, 60+/-10 years) survived until day 90, whereas 7 patients died in the control group (mean age, 67+/-7 years). Absolute hematoma size on admission was 58+/-29 mL (hypothermia) compared to 57+/-31 mL (control). In the hypothermia group, edema volume remained stable during 14 days (day 1, 53+/-43 mL; day 14, 57+/-45 mL), whereas edema significantly increased in the control group from 40+/-28 mL (day 1) to 88+/-47 mL (day 14). ICH continuously dissolved in both groups. Pneumonia rate was 100% in the hypothermia group and 76% in controls (P=0.08). No significant side effects of hypothermia were observed.
Hypothermia prevented the increase of peri-hemorrhagic edema in patients with large sICH.
BACKGROUND AND PURPOSE—Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital ...stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH.
METHODS—This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na <135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality.
RESULTS—The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients <48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05–4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1–10.6; P<0.001); thereafter, mortality rates were similar.
CONCLUSIONS—Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.
To assess changes in frequency, severity, complications, therapy and outcome of intracerebral hemorrhage in patients treated in stroke units in Austria, we evaluated data from the Austrian Stroke ...Unit Registry between 2008 and 2016.
Data of 6707 cases of ICH covering a time span of 9 years and including information on age, risk factors, pre-stroke modified Rankin Score (mRS), baseline stroke severity (NIHSS), complications, therapy, functional outcome, and mortality were extracted from the Austrian Stroke Unit Registry. A multivariate regularized logistic regression model and linear models for temporal dependence were computed for analyzing statistical inference and time trends. Bonferroni correction was applied to correct for multiple testing. Between 2008 and 2016, the proportion of ICH admissions to stroke units in Austria declined, with a shift among patients towards older age (>70 years, p = 0.04) and lower admission NIHSS scores. While no significant time trends in risk factors, pre-stroke mRS and medical complications were observed, therapeutic interventions declined significantly (p<0.001). Three-month mortality increased over the years independently (p = 0.003).
Despite declining incidence and clinical severity of ICH we observed a clear increase in three-month mortality. This effect seems to be independent of predictors including age, admission NIHSS, pre-morbid MRS, or medical complications. The observations from this large retrospective database cohort study underline an urgent call for action in the therapy of ICH.
Background
Intracerebral hemorrhage (ICH) is a devastating disease with ICH volume being the main predictor of poor outcome. The prognostic role of perihemorrhagic edema (PHE) is still unclear; ...however, available data are mainly derived from analyses during the first days after symptom onset. As PHE growth may continue up to 14 days after ICH, we evaluated PHE over a longer period of time and investigated its impact on short-term clinical outcome.
Methods
In this monocentric retrospective cohort study, patients with spontaneous supratentorial ICH were identified from our institutional data base. Different time points of CT scans were merged to time clusters for better comparison (day 1, 2–3, 4–6, 7–9, 10–12). Absolute volumes of ICH and PHE were obtained using a validated semiautomatic volumetric algorithm. Clinical outcome at discharge was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor).
Results
220 patients (83 with favorable, 137 with poor outcome) were included in the final analysis. Mean ICH volume on admission was 22.8 standard deviation (SD) 24.6 cm
3
. Mean absolute PHE volume on admission was 22.5 (SD 20.8) cm
3
and increased to a mean peak volume of 38.1 (SD 31.4) cm
3
during 6.7 (SD 4.1) days on average. Besides GCS on admission, functional status before ICH, peak hematoma volume, lobar localization and fever burden, and high peak PHE volume predicted poor outcome at discharge OR 0.977 (95 % CI 0.957–0.998) in the multivariable analysis.
Conclusions
PHE may have a negative impact on short-term functional outcome after ICH and therefore represent a possible treatment target.
Therapeutic hypothermia (TH) is an established treatment after cardiac arrest and growing evidence supports its use as neuroprotective treatment in stroke. Only few and heterogeneous studies exist on ...the effect of hypothermia in subarachnoid hemorrhage (SAH). A novel approach of early and prolonged TH and its influence on key complications in poor-grade SAH, vasospasm and delayed cerebral ischemia (DCI) was evaluated.
This observational matched controlled study included 36 poor-grade (Hunt and Hess Scale >3 and World Federation of Neurosurgical Societies Scale >3) SAH patients. Twelve patients received early TH (<48 h after ictus), mild (35°C), prolonged (7 ± 1 days) and were matched to 24 patients from the prospective SAH database. Vasospasm was diagnosed by angiography, macrovascular spasm serially evaluated by Doppler sonography and DCI was defined as new infarction on follow-up CT. Functional outcome was assessed at 6 months by modified Rankin Scale (mRS) and categorized as favorable (mRS score 0-2) versus unfavorable (mRS score 3-6) outcome.
Angiographic vasospasm was present in 71.0% of patients. TH neither influenced occurrence nor duration, but the degree of macrovascular spasm as well as peak spastic velocities were significantly reduced (p < 0.05). Frequency of DCI was 87.5% in non-TH vs. 50% in TH-treated patients, translating into a relative risk reduction of 43% and preventive risk ratio of 0.33 (95% CI 0.14-0.77, p = 0.036). Favorable functional outcome was twice as frequent in TH-treated patients 66.7 vs. 33.3% of non-TH (p = 0.06).
Early and prolonged TH was associated with a reduced degree of macrovascular spasm and significantly decreased occurrence of DCI, possibly ameliorating functional outcome. TH may represent a promising neuroprotective therapy possibly targeting multiple pathways of DCI development, notably macrovascular spasm, which strongly warrants further evaluation of its clinical impact.
Although outcome in intracerebral hemorrhage (ICH) patients is generally not improved by surgical intervention, the use of minimally invasive surgery (MIS) has shown promising results. However, ...vitamin K antagonist (VKA)-related ICH patients are underrepresented in surgical treatment trials. We therefore assessed the safety and efficacy of a bedside MIS approach including local application of urokinase in VKA-related ICH.
Patients with a VKA-related ICH > 20 ml who received bedside hematoma evacuation treatment (
= 21) at the University Medical Center Freiburg were retrospectively included for analysis and compared to a historical control group (
= 35) selected from an institutional database (University Medical Center Erlangen) according to identical inclusion criteria. Propensity score matching was performed to obtain comparable cohorts. The evolution of hematoma and peri-hemorrhagic edema (PHE) volumes, midline shift, and the occurrence of adverse events were analyzed. Furthermore, we assessed the modified Rankin Scale and NIHSS scores recorded at discharge.
Propensity score matching resulted in 16 patients per group with well-balanced characteristics. Median ICH volume at admission was 45.7 (IQR: 24.2-56.7) ml in the control group and 48.4 (IQR: 28.7-59.6) ml in the treatment group (
= 0.327). ICH volume at day 7 was less pronounced in the treatment group MIS: 23.2 ml (IQR: 15.8-32.3) vs. control: 43.2 ml (IQR: 27.5-52.4);
= 0.013, as was the increase in midline shift up to day 7 MIS: -3.75 mM (IQR: -4.25 to -2) vs. control: 1 mM (IQR: 0-2);
< 0.001. No group differences were observed in PHE volume on day 7 MIS: 42.4 ml (IQR: 25.0-72.3) vs. control: 31.0 ml (IQR: 18.8-53.8);
= 0.274 or mRS at discharge MIS: 5 (IQR: 4-5) and 5 (IQR: 4-5);
= 0.949. No hematoma expansion was observed. The catheter had to be replaced in 1 patient (6%).
Bedside catheter-based hematoma evacuation followed by local thrombolysis with urokinase appears to be feasible and safe in cases of large VKA-related ICH. Further studies that assess the functional outcome associated with this technique are warranted.
DRKS00007908 (German Clinical Trial Register; www.drks.de).
Background and purposeIntraventricular haemorrhage (IVH) is an independent predictor of poor outcome in spontaneous intracerebral haemorrhage (ICH). Larger IVH volume and increasing number of ...affected ventricles have been associated with worse prognosis, however, little is known about the prognostic value of blood volume in the different parts of the ventricular system. Therefore, the correlation of IVH volume in the third, fourth and lateral ventricles with outcome in patients with ICH and severe IVH, treated with intraventricular fibrinolysis (IVF), was investigated.MethodsPatients with ICH <40 ml, severe IVH and acute hydrocephalus were treated with IVF. The course of IVH volume for each ventricle was measured by CT based volumetry. Outcome at 90 days was assessed by a telephone follow-up survey and correlated with initial IVH volume.Results50 patients aged 62.5±10.3 years with spontaneous ICH (12.5±10.8 ml) and severe IVH (33.5±25 ml) were included. Clearance of the third and fourth ventricle from blood occurred after 3±1.9 days. Initial IVH volume in the third ventricle (3.8±3.3 ml) was predictive for poor outcome (OR 2.6 per ml, p=0.02). Correlation between larger IVH volume in the fourth ventricle and poor outcome showed a trend towards significance (p=0.07). Total IVH volume and lateral ventricle IVH volume were not correlated with outcome.ConclusionDespite rapid clot removal, initial IVH volume in the third ventricle was a strong and independent negative predictor. This is possibly explained by irreversible damage of brainstem structures by the initial mass effect of IVH.
The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH).
Patients with ...intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7 ± 1 and 10 ± 1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months.
The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3, P=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4 ± 4.2 mL versus 8.8 ± 8.1 mL; P=0.01) and 10 (1.4 ± 2.8 mL versus 4.9 ± 65.8 mL; P=0.005). Total clot half-life was 78 ± 43 hours in the low-dose and 56 ± 25 hours in the high-dose group (P=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months.
Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).
Summary
Glutamic acid decarboxylase (GAD) is the enzyme which catalyzes the production of gamma aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system (CNS). ...There is increasing evidence that severe GAD autoimmunity may be associated with refractory epilepsy. Immunomodulation and GABAergic drugs have been suggested as treatment options. We report here for the first time on a patient with sudden onset of refractory status epilepticus in the presence of strong intrathecal anti‐GAD antibody synthesis who was successfully treated with cyclophosphamide, and give an overview of available data on epilepsy associated with GAD autoimmunity.
Abstract
BACKGROUND:
Lumbar drainage (LD) represents a promising treatment strategy for prevention of vasospasm after aneurysmal subarachnoid hemorrhage (SAH).
OBJECTIVE:
To report on transient ...herniation caused by lumbar overdrainage in 3 patients with severe SAH who were treated with early LD within an ongoing feasibility study.
METHODS:
Patients with first-time aneurysmal SAH received LD within 72 hours of symptom onset, after aneurysm clipping or coiling. LD, with a target drainage amount of 5 to 10 mL, was continued for 6 to 9 days. External ventricular drainage (EVD) was begun on admission when hydrocephalus was present. With both catheters in place, intracranial pressure (ICP) and lumbar pressure (LP) were monitored simultaneously.
RESULTS:
Three of 22 patients developed a progressive lumboventricular pressure gradient, likely due to cerebrospinal fluid (CSF) overdrainage. Two patients showed signs of herniation. Clamping of LD resulted in complete reversal of symptoms in those patients. The lumboventricular pressure gradient began to evolve at least 12 hours before clinical symptoms developed, and gradually disappeared in all 3 patients after LD clamping.
CONCLUSION:
Lumbar overdrainage should be avoided in severe SAH, and lumboventricular pressure measurement may be a useful monitoring tool. Herniation due to lumbar overdrainage is a feared complication that can be avoided by following a strict LD management protocol.
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