Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

Clinical Impact and Predictors of Aneurysmal Rebleeding in Poor-Grade Subarachnoid Hemorrhage: Results From the National POGASH Registry.

BACKGROUND: Scarce data are available regarding rebleeding predictors in poor-grade aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVES: To investigate predictors and clinical impact of rebleeding in a national multicentric poor-grade aSAH. METHODS: Retrospective analysis of prospectively collected data from the multicentric Poor Grade Aneurysmal Subarachnoid Hemorrhage Study Group (POGASH) registry of consecutive patients treated from January 1, 2015, to June 30th, 2021. Grading was defined as pretreatment World Federation of Neurological Surgeons grading scale IV-V. Ultra-early vasospasm (UEV) was defined as luminal narrowing of intracranial arteries not due to intrinsic disease. Rebleeding was defined as clinical deterioration with evidence of increased hemorrhage on subsequent computed tomography scans, fresh blood from the external ventricular drain, or deterioration before neuroradiological evaluation. Outcome was assessed by the modified Rankin Scale. RESULTS: Among 443 consecutive World Federation of Neurological Surgeons grades IV-V patients with aSAH treated within a median of 5 (IQR 4-9) hours since onset, rebleeding occurred in 78 (17.6%). UEV (adjusted odds ratio [OR] 6.8, 95% CI 3.2-14.4; P < .001) and presence of dissecting aneurysm (adjusted OR 3.5, 95% CI 1.3-9.3; P = .011) independently predicted rebleeding while history of hypertension (adjusted OR 0.4, 95% CI 0.2-0.8; P = .011) independently reduced its chances. 143 (32.3) patients died during hospitalization. Rebleeding emerged, among others, as an independent predictor of intrahospital mortality (adjusted OR 2.2, 95% CI 1.2-4.1; P = .009). CONCLUSION: UEV and presence of dissecting aneurysms are the strongest predictors of aneurysmal rebleeding. Their presence should be carefully evaluated in the acute management of poor-grade aSAH.

Unruptured Versus Ruptured AVMs: Outcome Analysis from a Multicentric Consecutive Series of 545 Surgically Treated Cases.

BACKGROUND: Recent literature strongly challenged indications to perform preventive surgery in unruptured arteriovenous malformation (AVM) claiming that invasive AVM treatment is associated with a significant risk of complications and thus conservative management may be a preferable alternative in many patients. On the other hand, the recent improvement of surgical instrumentation and treatment strategies (both surgical and interventional) yielded better outcomes than those achieved only a decade ago. Therefore, even among specialists, a wide variety of opinions, concerning the treatment of unruptured AVM, can be found. METHODS: This multicenter retrospective study analyzes a consecutive series of 545 surgically treated AVMs in 10 different hospitals in Italy. RESULTS: Patients with AVMs treated after hemorrhage had an unfavorable (modified Rankin Scale score >1) outcome in more than one third (37.69%) of the cases. Conversely, with proper indications, unruptured AVMs treated preventively have a good outcome in 93.8% of cases, increasing to 95.7%, with no death, if only Spetzler-Martin grades 1-3 are considered (P < 0.05). Outcomes on discharge significantly (P < 0.05) improve at 6 months with the disappearance of many of the initial neurologic deficits that turn out to be transient. CONCLUSIONS: In unruptured low-risk AVMs (Spetzler-Martin grades 1-3), over time, the risk of surgery-associated neurologic deficits becomes lower than that linked to spontaneous hemorrhage, with a crossover point at 6.5 years. Because the average bleeding age is less than 45 years, preventive surgery can be advocated to safeguard the patient and overcome the risks associated with the natural history of AVMs.

What is hiding behind bubbles of air? An unusual Streptococcus pyogenes meningitis.

Streptococcus pyogenes is a rare but aggressive cause of meningitis, which often evolves in a poor outcome with fatal consequences. Although lumbar puncture and CT scan of the brain are the gold standard of diagnosis of cerebral infections, they can have some limitations. We report and describe the clinical history and neuroimaging of a 36-year-old woman admitted to the emergency department of our hospital three days after the onset of earache and otorrhoea. When the patient developed an emergent refractory status epilepticus, the CT scan of the brain showed an unusual pneumocephalus. However, the MRI study of the brain revealed a pachymeningitis with partial thrombosis of the right transverse sinus and subdural empyema due to a S. pyogenes otitis media. Prompt diagnosis and the specific findings of the MRI allowed rapid correct treatment and thus led to a good outcome for the patient.

Shc3 affects human high-grade astrocytomas survival.

A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of neuronal precursors into postmitotic neurons. Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3. Under normal conditions Shc3 is never expressed by glial cells. We now show that in human astrocytomas and glioblastomas, the normal pattern of expression of Shc1/Shc3 is totally subverted, both proteins being present at the same time and in the same cells. Our data indicate that Shc3 is maximally expressed, together with Shc1, in glioblastoma, a highly proliferative tumor with little, if any, indication of neuronal differentiation. In primary cultures of glioblastoma, tumor cells maintain Shc1 expression but downregulate Shc3. Analysis of the phosphorylation status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is tyrosine phosphorylated. Finally, we found that the expression of truncated variants of Shc3 with dominant-negative effects in human high-grade glioma cells that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation and increased apoptosis, thus resulting in impaired survival of the transfected cells. These data suggest that Shc molecules play an important role in glioblastoma cell growth and survival.