Kuo-Chuan Wang

Clinical Significance of Posterior Circulation Changes after Revascularization in Patients with Moyamoya Disease

Objective: It has been noted that the posterior circulation serves as an important source of collateral blood supply in moyamoya disease. Since most of the literature has focused on non-operative cases and many symptomatic patients receive surgical revascularization, we evaluated the posterior circulation changes after revascularization and found that progressive posterior cerebral artery (PCA) steno-occlusive changes after revascularization caused cerebral hemodynamic compromise and clinical deterioration in a significant portion of patients. Methods: Twenty-three moyamoya disease patients with ischemic presentation who received revascularization with complete angiography and xenon CT during a minimum of 3 years’ clinical follow-up were enrolled. Revascularization was performed in 38 hemispheres. Pre- and postoperative angiography were reviewed to determine the internal carotid artery (ICA) stage, PCA stage, leptomeningeal collateral (LMC) grade, and Matsushima synangiosis grade. The postoperative regional cerebral blood flow (CBF) and cerebral vascular reserve (CVR) were recorded and correlated with angiographic findings and clinical outcome. Results: Progression of ICA staging was noted in 23 sides (55.2%), and progression of PCA staging was noted in 18 sides (47.4%). Among the 18 cases of PCA stage progression, an associated decrease in LMC grade was noted in 12 sides (66.7%). These changes were associated with decreased regional CBF and CVR, which also explained the recurrent ischemic symptoms in 27.8% of these patients. In contrast, LMC grade increased in 15 (65.2%) sides of patients with ICA progression. Conclusions: Progressive steno-occlusive change in the PCA after revascularization is associated with a reduction in LMC blood flow and cerebral ischemia in moyamoya patients. This phenomenon might cause recurrent ischemic symptoms in 27.8% of patients.

Brain stem cavernous malformations

We retrospectively reviewed the clinical experience of 30 patients with brain stem cavernous malformations (BSCM) treated operatively and non-operatively at our hospital between 1983 and 2005 to elucidate the natural history of BSCM and the factors that affect surgical outcome. Inpatient charts, imaging studies, operative records, and follow-up results were evaluated. The average follow up was 48.5 months. Twenty-two patients (73.3%) received surgical extirpation and of these 86.4% improved or stabilized and 13.6% deteriorated with permanent or severe morbidity. There was no mortality. Size, preoperative status, and surgical timing were factors related to surgical outcome. In the non-operative group, 50% of the patients were the same or better, 25% deteriorated, and 25% died. With appropriate patient selection, resection of BSCM can be achieved with acceptable morbidity compared with the ominous natural history of these lesions.

Risk profile of patients with poor-grade aneurysmal subarachnoid hemorrhage using early perfusion computed tomography.

OBJECTIVE To determine whether perfusion computed tomography (CT) is useful for identifying patients with poor-grade subarachnoid hemorrhage (SAH) with reversible etiologies and whether early obliteration in patients with poor-grade aneurysmal SAH leads to favorable outcomes. METHODS Patients with new-onset aneurysmal SAH in World Federation of Neurological Surgeons (WFNS) grade IV or V neurologic condition who had perfusion CT performed at admission were eligible for the study. The study retrospectively enrolled 38 patients seen between January 2007 and July 2009. The decision to perform an early obliteration was made by the family after a discussion with the neurosurgeons, neurointensivists, and interventional radiologists. The functional outcomes were correlated with the Glasgow Outcome Scale (GOS) at 6 months, and quantitative perfusion CT data were collected. RESULTS This study included 10 (26%) grade IV and 28 (74%) grade V patients. Favorable outcomes occurred in 19 (50%) patients, and 11 (29%) patients died. After a multivariate logistic regression analysis of the parameters, older age (odds ratio 1.104, P = 0.0317), bilateral prolonged mean transient time (MTT) at the thalami (odds ratio 4.155, P = 0.0362), and early obliteration (odds ratio 0.098, P = 0.003) were predictive of poor outcome. CONCLUSIONS Early bilateral prolonged MTT at the thalami and old age are associated with a poor outcome. Early obliteration benefits a significant portion of SAH patients.

Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan.

Moyamoya disease (MMD) is a disorder characterized by stenosis of bilateral internal carotid arteries with compensatory angiogenesis of the perforating blood vessels. Familial transmission in MMD is common. Recently, mutations in human RNF213 and ACTA2 genes were identified to be responsible for MMD. The present study was to determine whether Taiwanese MMD patients carried mutations in these two genes. Of the 36 MMD patients, eleven was found to have RNF213 mutations. Direct genetic sequencing identified four different RNF213 mutations in the 11 patients from 8 families: five with a p.R4810K, one with p.A1622V, one with p.V3933M, and the other one with p.R4131C. The latter three represent novel missense mutations. No mutation in ACTA2 gene was identified. Clinically, cerebral infarction was common in patients with an RNF213 mutation (9/11). In addition, four mutant patients had developmental delay (4/11) and two had mental dysfunction (2/11). The magnetic resonance angiography of asymptomatic mutant carriers demonstrated high incidence of multiple stenosis of intracranial vessels (3/6, 50%). Since 30.6% (11/36) of Taiwanese moyamoya patients carry an RNF213 mutation and intracranial arterial stenosis was found in half of the asymptomatic mutant carriers, it is suggested that the RNF213 mutation should form part of the diagnostic workup for MMD in clinical practice.

The hemodynamic effects during sustained low-efficiency dialysis versus continuous veno-venous hemofiltration for uremic patients with brain hemorrhage: a crossover study

OBJECT Hemodynamic instability occurs frequently during dialysis treatment and remains a significant cause of patient morbidity and mortality, especially in patients with brain hemorrhage. This study aims to compare the effects of hemodynamic parameters and intracranial pressure (ICP) between sustained low-efficiency dialysis (SLED) and continuous veno-venous hemofiltration (CVVH) in dialysis patients with brain hemorrhage. METHODS End-stage renal disease (ESRD) patients with brain hemorrhage undergoing ICP monitoring were enrolled. Patients were randomized to receive CVVH or SLED on the 1st day and were changed to the other modality on the 2nd day. The ultrafiltration rate was set at between 1.0 kg/8 hrs and 1.5 kg/8 hrs according to the patients fluid status. The primary study end point was the change in hemodynamics and ICP during the dialytic periods. The secondary end point was the difference between cardiovascular peptides and oxidative and inflammatory assays. RESULTS Ten patients (6 women; mean age 59.9 ± 3.6 years) were analyzed. The stroke volume variation was higher with SLED than CVVH (generalized estimating equations method, p = 0.031). The ICP level increased after both SLED and CVVH (time effect, p = 0.003) without significant difference between modalities. The dialysis dose quantification after 8-hour dialysis was higher in SLED than CVVH (equivalent urea clearance by convection, 62.7 ± 4.4 vs 50.2 ± 3.9 ml/min; p = 0.002). Additionally, the endothelin-1 level increased after CVVH treatment (p = 0.019) but not SLED therapy. CONCLUSIONS With this controlled crossover study, the authors provide the pilot evidence that both SLED and CVVH display identical acute hemodynamic effects and increased ICP after dialysis in brain hemorrhage patients. CLINICAL TRIAL REGISTRATION NO.: NCT01781585 (ClinicalTrials.gov).

Hyperacute cerebral aneurysm rerupture during CT angiography

OBJECT The object of this study was to identify the clinical features and outcomes of a subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) who had active contrast extravasation from a ruptured aneurysm during initial cerebral CT angiography (CTA). METHODS The authors performed a retrospective study of spontaneous SAH cases involving patients treated at their institute. They identified 9 cases in which active contrast extravasation was evident on the initial CT angiogram. Another 12 similar cases were also identified in a literature review and data was gathered from these cases to evaluate the outcomes. RESULTS Analysis of all 21 cases revealed that the overall outcomes in cases characterized by active aneurysmal bleeding during CTA were poor. Seventy-six percent of patients had unfavorable results. Patients who showed poor neurological status at presentation died no matter what kind of treatment they received. In contrast, patients who presented with good neurological status initially had a chance of favorable outcome. Among the patients with good initial neurological status, most demonstrated rapid deterioration of their condition during the CTA examination; only those who received immediate and effective decompressive surgery and aneurysm obliteration had good results. CONCLUSIONS Active aneurysmal rebleeding during CTA is an uncommon but devastating event. Though the mortality of this distinct group of patients remains high, a clinical subgroup may benefit from immediate surgery. Patients with good initial neurological status who show rapid neurological deterioration may still have a favorable outcome if they undergo timely and successful decompressive surgery and proper aneurysm obliteration. Patients who present with poor neurological status do badly, and there is no effective treatment for such patients.

Prognostic value of intrathecal heme oxygenase-1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage

OBJECT Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. METHODS Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. RESULTS The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy). CONCLUSIONS The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.

Acute cerebral ischemia following intraventricular hemorrhage in moyamoya disease: early perfusion computed tomography findings : Case report

The authors present a rare case of an infarction complication 15 days following acute intraventricular bleeding due to moyamoya disease. Before the infarction occurred, perfusion CT imaging disclosed early but reversible ischemic injury on the day of hemorrhage. Dehydration and hypotension are both possibly contributing factors of progressive injury from reversible ischemia due to infarction. Although the patient underwent successful bypass surgery, 1 month after the ictus the neurobehavior evaluation still showed marked executive dysfunction. The authors address that, in hemorrhagic-type moyamoya disease, early perfusion CT scanning is not only a powerful tool to identify the high-risk group of patients who could experience subacute infarction, but also alarms neurosurgeons to eliminate any predisposing factors when it shows reversible ischemic injuries.

A Larger Dose of Vancomycin Is Required in Adult Neurosurgical Intensive Care Unit Patients Due to Augmented Clearance.

Background: The objective of this study was to explore the pharmacokinetics of vancomycin and determine an appropriate dosage regimen for vancomycin in adult neurosurgical intensive care unit (ICU) patients. Methods: First, a 20-month therapeutic drug monitoring database at a medical center was used to retrospectively analyze the pharmacokinetic parameters of vancomycin in adult neurosurgical patients. Significant covariates were selected through Pearson or Spearman correlation tests and multiple linear regressions. Pharmacokinetic models were built using significant covariates to predict vancomycin clearance. Second, a 12-month prospective cohort of neurosurgical ICU patients was recruited to validate the models. Urine and cerebrospinal fluid samples were collected, and vancomycin concentrations were determined using a high-performance liquid chromatography assay. The relation between the model-predicted and observed pharmacokinetic parameters was assessed by Pearson correlation. Results: In the retrospective cohort, 98 sets of peak/trough serum concentrations obtained from 73 patients were analyzed. These patients had a mean age of 54 ± 16 years, an estimated creatinine clearance (eClCr) of 83 ± 29 mL/min, a total vancomycin clearance (ClVan) of 101 ± 41 mL/min, and a volume of distribution (Vd) of 0.93 ± 0.27 L/kg. In a subgroup analysis, the ClVan of ICU patients was higher than the ClVan of non-ICU patients (1.57 ± 0.34-fold versus 1.16 ± 0.32-fold of eClCr, P < 0.05). Fifteen patients enrolled in the prospective cohort had an average age of 67 ± 12 years, an eClCr of 108 ± 44 mL/min, a ClVan of 112 ± 29 mL/min, and a Vd of 1.03 ± 0.55 L/kg. Conclusions: Adult neurosurgical ICU patients have a significantly elevated ClVan. In this study, 2 dosing equations were derived to achieve optimal serum vancomycin concentrations for this special population.

Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage.

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fishers grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005–1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fishers grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.