Sepide Kashefiolasl

Non-aneurysmal subarachnoid hemorrhage in 173 patients: a prospective study of long-term outcome.

In some patients with subarachnoid hemorrhage (SAH) a bleeding source cannot be identified. Perimesencephalic (PM) SAH is assumed to have an excellent outcome. Our objective was to analyze the long‐term physical and psychological outcome of patients after non‐aneurysmal SAH.

Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non-aneurysmal subarachnoid hemorrhage: the underestimated risk of Fisher 3 blood distribution

Objective Recent data have shown increasing numbers of non-aneurysmal subarachnoid hemorrhage (NASAH). However, data are limited and often only small series have been published. Our objective was to analyze the rate of cerebral vasospasm (CVS), delayed cerebral infarction (DCI), and their influence on the clinical outcome, especially in patients with diffuse Fisher 3 bleeding pattern NASAH (Fi3). Methods Between 1999 and 2014, 225 patients had NASAH. CVS, DCI, and outcome (according to the modified Rankin Scale at 6 months) were analyzed retrospectively. Patients were stratified according to the bleeding type. After univariate analysis a multivariate analysis was performed and NASAH Fi3 was also compared with aneurysmal SAH Fi3. Results Patient characteristics and the outcome of perimesencephalic (PM) and non-PM (NPM) SAH were similar. Excluding Fi3, PM and NPM without Fi3 had similar patient characteristics, clinical course, and outcome. In particular, the Fi3 subgroup had a significantly increased risk of CVS, DCI, unfavorable outcome, hydrocephalus, and death. Early hydrocephalus was associated with Fi3 and intraventricular hemorrhage. The multivariate regression model showed the variables elderly patients, Fi3, and early hydrocephalus as independent and significant predictors for an unfavorable outcome. A further comparison of NASAH Fi3 with aneurysmal SAH Fi3 showed similar characteristics, CVS rate, and mortality. Conclusions Patients with NASAH without a Fi3 bleeding pattern had a similar excellent outcome to patients with PM-SAH. Patients with Fi3 had a high risk for early hydrocephalus, CVS, DCI, and an unfavorable outcome, similar to patients with aneurysmal SAH. After multivariate analysis, early hydrocephalus, elderly patients, and Fi3 were identified as negative prognostic factors. Therefore, patients with Fi3 are at risk and need careful clinical observation.

Benefit of Stereotactic Procedures in a Series of 43 Children

Objectives: Stereotactic biopsies are procedures that enable neurosurgeons to obtain tissue samples of brain tumors located in eloquent areas with a low risk of perioperative complications. In this study, we examined stereotactic procedures (STX) in children. We focused on effectiveness, safety, and histopathological results to evaluate the benefits of the procedure. Methods: We performed a retrospective analysis of our prospective database and included 43 children aged less than 18 years who underwent STX between 1998 and May 2015. All MRIs were evaluated by a single, experienced neuroradiologist. For all biopsies, Leksell stereotactic frame was used and fixed to the children’s head with four pins. Entry and targetpoints were calculated by BrainLab navigation system. We assessed age, tumor localization, number of samples, histological diagnosis, and postoperative treatment. Results: Median age of the patients was 11 years (range 1-18 years), and median number of tissue samples taken was 12 (range 1 with mere puncture of a cyst to 36). Histopathological examination revealed a final diagnosis in all patients. 3 patients underwent puncture of a cyst. 27 patients had a postoperative imaging. Only in 3 patients, CT scan revealed blood in the area where the biopsy had been taken. All bleedings were small and without clinical sequelae. Conclusion: Stereotactic procedures are accurate and save surgeries to obtain tumor tissue from eloquent areas to base further therapy on. This not only applies to adults but also to children of all ages.

Effect of heparin on secondary brain injury in patients with subarachnoid hemorrhage: an additional ‘H’ therapy in vasospasm treatment

Objective Secondary brain injury leads to high morbidity and mortality rates in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, evidence-based treatment strategies are sparse. Since heparin has various effects on neuroinflammation, microthromboembolism and vasomotor function, our objective was to determine whether heparin can be used as a multitarget prophylactic agent to ameliorate morbidity in SAH. Methods Between June 1999 and December 2014, 718 patients received endovascular treatment after rupture of an intracranial aneurysm at our institution; 197 of them were treated with continuous unfractionated heparin in therapeutic dosages after the endovascular procedure. We performed a matched pair analysis to evaluate the effect of heparin on cerebral vasospasm (CVS), cerebral infarction (CI), and outcome. Results The rate of severe CVS was significantly reduced in the heparin group compared with the control group (14.2% vs 25.4%; p=0.005). CI and multiple ischemic lesions were less often present in patients with heparin treatment. These effects were enhanced if patients were treated with heparin for >48 hours, but the difference was not significant. Favorable outcome at 6-month follow-up was achieved in 69% in the heparin group and in 65% in the control group. Conclusions Patients receiving unfractionated continuous heparin after endovascular aneurysm occlusion have a significant reduction in the rate of severe CVS, have CI less often, and tend to have a favorable outcome more often. Our findings support the potential beneficial effects of heparin as a multitarget therapy in patients with SAH, resulting in an additional ‘H’ therapy in vasospasm treatment.

Hematoma expansion in experimental intracerebral hemorrhage is not altered by peracute treatment with recombinant tissue plasminogen activator

Recombinant tissue-type plasminogen activator (rt-PA) is the mainstay of acute stroke treatment and the only approved medical therapy so far. Because of its fibrinolytic action, it is presumed to aggravate intracerebral hemorrhage (ICH). Since clinical features do not discriminate between ischemic stroke and ICH, brain imaging is strictly required before the initiation of thrombolysis. A recent study has shown that rt-PA does not worsen (primary) ICH in two different experimental mouse models. Here, we further explored this surprising finding and examined hematoma expansion and long-term outcome after rt-PA treatment in a murine model of ICH. We induced ICH by collagenase injection into the right basal ganglia of C57BL/6 mice. At 30 min, 90 min or 4h after ICH induction, respectively, mice were treated with vehicle or 10mg/kg rt-PA. In parallel, we administered the vascular tracer Evans Blue (EB) and sacrificed the mice 2h after injection to assess EB extravasation as a marker of ongoing bleeding and rt-PA induced rebleeding. Additionally, we observed mice which were treated with vehicle or rt-PA 30 min after ICH induction for 72 h and quantified functional outcome and hematoma volume. EB extravasation was highest in the groups that were treated after 30 min and decreased thereafter according to a cessation of active bleeding. At all three time points covering the early phase of ICH, treatment with rt-PA did not increase EB extravasation. In the 72 h observation, there was also no difference in functional outcome and hematoma volume. In our experimental study, we were not able to demonstrate that peracute rt-PA treatment in (primary) ICH has detrimental effects on hematoma expansion, hematoma volume or functional outcome. This finding needs careful consideration in future translational studies.

Non-aneurysmal non-perimesencephalic subarachnoid hemorrhage: effect of rehabilitation at short-term and in a prospective study of long-term follow-up

Background: A recently published prospective study identified an impaired outcome of patients with non-perimesencephalic (NPM) subarachnoid hemorrhage (SAH). Our objective was to analyze the long-term outcome of patients with subsequent rehabilitation after NPM SAH. Methods: A comparison of patients with NPM SAH receiving subsequent in-patient rehabilitation was done at discharge (using the modified Rankin scale (mRS)), short-term outcome after 6 months (mRS), and prospectively using a questionnaire (short-form health survey with 36 questions (SF-36)), which was sent to 66 patients. Results: Thirty-seven patients answered the SF-36, on average 6.3 years after ictus (range 1.5–14 years). After NPM SAH, the mRS is impaired. Patients with subsequent rehabilitation had a significant better improvement until short-term follow-up. Until long-term outcome, the psychological items were non-significantly reduced, whereas all physical items (physical functioning, role limitations because of physical health problems, bodily pain, and general health perceptions) were significantly decreased compared to the standard population. In patients with subsequent rehabilitation, all items were only non-significantly reduced. About 16% of the patients developed secondary neurological and/or psychiatric diseases. Conclusions: The quality of life (QoL) is decreased after NPM SAH. In the long-term follow-up, a significant reduction in physical items was identified. Due to subsequent in-patient rehabilitation after NPM SAH, the impairment can be improved significantly until short-term follow-up. Whereas patients with NPM SAH had a significantly decreased QoL at long-term follow-up, for patients with rehabilitation, the QoL was only slightly (non-significantly) reduced. Therefore, patients should receive subsequent rehabilitation after NPM SAH to improve the functional short-term outcome (mRS) and long-term QoL. www.clinicaltrials.gov (Identifier No. NCT02334657).

A benchmark approach to hemorrhage risk management of cavernous malformations

Objective Despite the low annual risk of hemorrhage associated with a cavernous malformation (CM) (0.6%–1.1% per year), the risk of rehemorrhage rate and severity of neurologic deficits is significantly higher; therefore, we aimed to evaluate the rupture risk of CMs depending on various factors. Methods We retrospectively analyzed medical records of all patients with CM admitted to our institution between 1999 and April 2016. Cavernoma volume, location of the lesion, existence of a developmental venous anomaly (DVA), number of cavernomas, and patient characteristics (sex, age, hypertension, and antithrombotic therapy) were assessed. Results One hundred fifty-four patients with CM were included; 89 (58%) ruptured CMs were identified. In statistical univariable analysis, the existence of a DVA was significantly higher in the ruptured cavernoma group (p < 0.001; odds ratio [OR] 4.6). A multivariable analysis of all included independent risk factors designated young age (<45 years) (p < 0.05; OR 2.2), infratentorial location (p < 0.01; OR 2.9), and existence of a DVA (p < 0.0001; OR 4.7) with significantly higher risk of rupture in our patient cohort. A separate analysis of these anatomical locations, supratentorial vs infratentorial, indicated that the existence of a DVA (p < 0.01; OR 4.16) in ruptured supratentorial cases and CM volume (≥1 cm3) (p < 0.0001; OR 3.5) in ruptured infratentorial cases were significant independent predictors for hemorrhage. Conclusions Young age (<45 years), infratentorial location, and the presence of a DVA are associated with a higher hemorrhage risk. CM volume (≥1 cm3) and the existence of a DVA were independently in accordance with the anatomical location high risk factors for CM rupture.

MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH

Background Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH. Methods We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA. Results 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI. Conclusion Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.

Graphite furnace atomic absorption spectrophotometry—A novel method to quantify blood volume in experimental models of intracerebral hemorrhage

Intracerebral hemorrhage (ICH) accounts for 10% of all strokes and has a significantly higher mortality than cerebral ischemia. For decades, ICH has been neglected by experimental stroke researchers. Recently, however, clinical trials on acute blood pressure lowering or hyperacute supplementation of coagulation factors in ICH have spurred an interest to also design and improve translational animal models of spontaneous and anticoagulant-associated ICH. Hematoma volume is a substantial outcome parameter of most experimental ICH studies. We present graphite furnace atomic absorption spectrophotometric analysis (AAS) as a suitable method to precisely quantify hematoma volumes in rodent models of ICH.

Influence of ABO blood type on the outcome after non-aneurysmal subarachnoid hemorrhage

BackgroundIn patients with non-aneurysmal subarachnoid hemorrhage (NA-SAH), the etiology is unknown and the bleeding source remains unidentified. However, the ABO blood type system has a profound role in patient’s hemostasis and thrombosis. To date, the aspect of ABO blood type in incidence, clinical course, and outcome after NA-SAH has not been investigated.MethodsIn this retrospective analysis, 81 patients with non-traumatic and non-aneurysmal subarachnoid hemorrhage treated between 2010 and 2014 at the author’s institution were included. WFNS admission status, cerebral vasospasm, delayed infarction, ventriculoperitoneal shunt necessity, the Fisher grade, and the modified Rankin Scale were analyzed for their association with ABO blood type. Four hundred seventy patients with aneurysmal subarachnoid hemorrhage served as a control group.ResultsThe AB blood type is more frequent in NA-SAH compared to aneurysmal patients and the German population (OR 2.45, p ≤ 0.05). Furthermore, NA-SAH with AB blood type showed a similar sequelae compared to aneurysmal patients in terms of shunt necessity (OR 2.00, p ≥ 0.05), cerebral vasospasm (OR 1.66, p ≥ 0.05), and delayed infarctions (OR 1.07, p ≥ 0.05).ConclusionThe clinical course of NA-SAH AB blood type patients shows similar severity as of aneurysmal subarachnoid hemorrhage. Therefore, patients with AB blood type should be under intensified observation.