Impact of Statins on Hematoma, Edema, Seizures, Vascular Events, and Functional Recovery After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The impact of statins on hematoma characteristics, perihemorrhagic edema (PHE), cardiovascular events, seizures, and functional recovery in patients with intracerebral hemorrhage (ICH) is insufficiently studied. METHODS: Patients with ICH of the prospective UKER-ICH (Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage) study (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03183167) were analyzed by multivariable regression modeling and propensity score matching, and PHE volumes were volumetrically assessed. Outcomes comprised hematoma characteristics, the impact of continuation, discontinuation, and initiation of statins on peak PHE extent, and the influence of statin treatment on the occurrence of seizures, cardiovascular adverse events, and functional recovery after ICH. RESULTS: A total of 1275 patients with ICH with information on statin treatment were analyzed. Statin treatment on hospital admission (21.7%) was associated with higher rates of lobar versus nonlobar ICH (odds ratio, 1.57 [1.03-2.40]; P=0.038). Initiation of statins after ICH was associated with increased peak PHE (ß=0.12, SE=0.06, P=0.008), whereas continuation versus discontinuation of prior statin treatment was not significantly associated with edema formation (P>0.10). There were no significant differences in the incidence of remote symptomatic seizures according to statin exposure during follow-up (statins: 11.5% versus no statins: 7.8%, subdistribution hazard ratio: 1.15 [0.80-1.66]; P=0.512). Patients on statins revealed less cardiovascular adverse events and more frequently functional recovery after 12 months (functional recovery: 57.7% versus 45.0%, odds ratio 1.67 [1.09-2.56]; P=0.019). CONCLUSIONS: Among statin users, lobar ICH occurs more frequently as compared with nonstatin users. While continuation of prior statin treatment appears to be safe regarding PHE formation, the initiation of statins during the first days after ICH may increase PHE extent. However, statins should be initiated thereafter (eg, at hospital discharge) to prevent cardiovascular events and potentially improve functional recovery.

Long-Term Complications and Influence on Outcome in Patients Surviving Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: While the short-term clinical outcome of patients with subarachnoid hemorrhage (SAH) is well described, there are limited data on long-term complications and their impact on social reintegration. This study aimed to assess the frequency of complications post-SAH and to investigate whether these complications attribute to functional and self-reported outcomes as well as the ability to return to work in these patients. METHODS: This retrospective single-center study included patients with atraumatic SAH over a 5-year period at a tertiary care center. Patients received a clinical follow-up for 12 months. In addition to demographics, imaging data, and parameters of acute treatment, the rate and extent of long-term complications after SAH were recorded. The functional outcome was assessed using the modified Rankin Scale (mRS; favorable outcome defined as mRS = 0-2). Further outcomes comprised self-reported subjective health measured by the EQ-5D and return to work for SAH patients with appropriate age. Multivariable analyses including in-hospital parameters and long-term complications were conducted to identify parameters independently associated with outcomes in SAH survivors. RESULTS: This study cohort consisted of 505 SAH patients of whom 405 survived the follow-up period of 12 months (i.e., mortality rate of 19.8%). Outcome data were available in 359/405 (88.6%) patients surviving SAH. At 12 months, a favorable functional outcome was achieved in 287/359 (79.9%) and 145/251 (57.8%) SAH patients returned to work. The rates of post-acute complications were headache (32.3%), chronic hydrocephalus requiring permanent ventriculoperitoneal shunting (VP shunt 25.4%) and epileptic seizures (9.5%). Despite patient's and clinical characteristics, both presence of epilepsy and need for VP shunt were independently and negatively associated with a favorable functional outcome (epilepsy: adjusted odds ratio [aOR] (95% confidence interval [95% CI]): 0.125 [0.050-0.315]; VP shunt: 0.279 [0.132-0.588]; both p < 0.001) as well as with return to work (aOR [95% CI]: epilepsy 0.195 [0.065-0.584], p = 0.003; VP shunt 0.412 [0.188-0.903], p = 0.027). Multivariable analyses revealed presence of headache, VP shunt, or epilepsy to be significantly related to subjective health impairment (aOR [95% CI]: headache 0.248 [0.143-0.430]; epilepsy 0.223 [0.085-0.585]; VP shunt 0.434 [0.231-0.816]; all p < 0.01). CONCLUSIONS: Long-term complications occur frequently after SAH and are associated with an impairment of functional and social outcomes. Further studies are warranted to investigate if treatment strategies specifically targeting these complications, including preventive aspects, may improve the outcomes after SAH.

Systemic inflammatory response syndrome and long-term outcome after intracerebral hemorrhage.

Objective: To investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018-2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature <36°C or >38°C, respiratory rate >20 per minute, heart rate >90 per minute, or white blood cell count <4,000/µL or >12,000/µL in the absence of infection. The primary outcome consisted of the modified Rankin Scale (mRS) at 3 and 12 months investigated by adjusted ordinal shift analyses. Bias and confounding were addressed by propensity score matching and multivariable regression models. Results: Of 780 patients with ICH, 21.8% (n = 170) developed SIRS during hospitalization. Patients with SIRS showed more severe ICH compared with those without; i.e., larger ICH volumes (18.3 cm3, interquartile range [IQR 4.6-47.2 cm3] vs 7.4 cm3, IQR [2.4-18.6 cm3]; p < 0.01), increased intraventricular hemorrhage (57.6%, n = 98/170 vs 24.8%, n = 79/319; p < 0.01), and poorer neurologic admission status (NIH Stroke Scale score 16, IQR [7-30] vs 6, IQR [3-12]; p < 0.01). ICH severity-adjusted analyses revealed an independent association of SIRS with poorer functional outcome after 3 (OR 1.80, 95% CI [1.08-3.00]; p = 0.025) and 12 months (OR 1.76, 95% CI [1.04-2.96]; p = 0.034). Increased ICH volumes on follow-up imaging (OR 1.38, 95% CI [1.01-1.89]; p = 0.05) and previous liver dysfunction (OR 3.01, 95% CI [1.03-10.19]; p = 0.04) were associated with SIRS. Conclusions: In patients with ICH, we identified SIRS to be predictive of poorer long-term functional outcome over the entire range of mRS estimates. Clinically relevant associations with SIRS were documented for previous liver dysfunction and hematoma enlargement.

Noninvasive Collateral Flow Velocity Imaging in Acute Ischemic Stroke: Intraindividual Comparison of 4D-CT Angiography with Digital Subtraction Angiography.

PURPOSE: The collateral status can be defined not only by its morphological extent but also by the velocity of collateral filling characterized by the relative filling time delay (rFTD). The aim of our study was to compare different methods of noninvasive visualization of rFTD derived from 4D-CT angiography (4D-CTA) with digital substraction angiography (DSA) and to investigate the correlation between functional and morphological collateral status on timing-invariant CTA. MATERIALS AND METHODS: 50 consecutive patients with acute occlusion in the M1 segment who underwent DSA for subsequent mechanical recanalization after multimodal CT were retrospectively analyzed. 4D-CTA data were used to assess the relative filling time delay between the A1 segment of the affected hemisphere and the sylvian branches distal to the occluded M1 segment using source images (4D-CTA-SI) and color-coded flow velocity visualization with prototype software (fv-CTA) in comparison to DSA. The morphological extent of collaterals was assessed on the basis of the Collateral Score (CS) on temporal maximum intensity projections (tMIP) derived from CT perfusion data. RESULTS: There was very good correlation of rFTD between fv-CTA and DSA (n = 50, r = 0.9, p < 0.05). Differences of absolute rFTD values were not significant. 4D-CTA-SI and DSA also showed good correlation (n = 50, r = 0.6, p < 0.05), but mean values of rFTD were significantly different (p < 0.05). rFTD derived from fvCTA and CS derived from timing-invariant CTA showed a negative association (R = - 0.5; P = 0.000). In patients with a favorable radiological outcome defined by a TICI score of 2b or 3, there was a significant negative correlation of CS and mRS at 3 months (R = - 0.4, P = 0.006). CONCLUSION: Collateral status plays an important role in the outcome in stroke patients. rFTD derived from 4D-CTA is a suitable parameter for noninvasive imaging of collateral velocity, which correlates with the morphological extent of collaterals. Further studies are needed to define valid thresholds for rFTD and to evaluate the diagnostic and prognostic value. KEY POINTS: · Collateral supply in anterior circulation stroke can be defined by the velocity of collateral filling. · Relative filling time delay (rFTD) can serve for quantitative measurement of collateral flow and correlates with the morphological extent of collaterals. · 4D-CTA is a suitable noninvasive imaging technique. CITATION FORMAT: · Muehlen I, Kloska SP, Gölitz P et al. Noninvasive Collateral Flow Velocity Imaging in Acute Ischemic Stroke: Intraindividual Comparison of 4D-CT Angiography with Digital Subtraction Angiography. Fortschr Röntgenstr 2019; 191: 827 - 835.

Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility.

Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor survival, such as Grk1 (G protein-coupled receptor kinase 1) and Pgc-1α (peroxisome proliferator-activated receptor γ, coactivator 1alpha). According to their daily dynamics, the genes identified could be clustered in two groups: those with peak expression during the second part of the day which are uniformly promoted to cycle by light/dark transitions and those with peak expression during the second part of the night which are predominantly driven by a clock. Since Grk1 and Pgc-1α belong in the first group, the present results support a concept in which transcriptional regulation of genes by ambient light contributes to the functional adjustment of photoreceptor cells over the 24-h period.

The retinal clock drives the expression of Kcnv2, a channel essential for visual function and cone survival.

PURPOSE: The gene Kcnv2 codes for the voltage-gated potassium channel subunit Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional voltage-gated potassium channels. Mutations in the Kcnv2 gene result in a retinal disorder designated "cone dystrophy with supernormal rod response (CDSRR)," revealing that Kcnv2 is essential for visual processing and cone survival. The aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under circadian regulation and may thus contribute to the clock-driven adjustment of photoreceptor function. METHODS: Expression of the genes was recorded in preparations of the whole retina and microdissected retinal neurons by using quantitative polymerase chain reaction and Western blot. RESULTS: The transcript levels of Kcnv2 and Kv2.1 in preparations of whole retina and photoreceptor cells were found to display daily rhythms, with elevated values during the night. For Kcnv2 this rhythm was shown to evoke a corresponding rhythm in Kv8.2, the protein product of this gene. The daily changes in retinal Kcnv2 and Kv2.1 mRNA levels persisted under constant darkness and are therefore driven by the endogenous retinal clock system, which itself is entrained by light. CONCLUSIONS: The present data provide evidence that the transcriptional regulation of Kcnv2 and Kv2.1 is a way through which the retinal clock system drives the functional adaptation of visual function to the marked daily changes in environmental lighting conditions.