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Raymond Sawaya, Mario Zuccarello and Robert Highsmith

✓ This study was undertaken to confirm the presence of alpha-1-antitrypsin (α 1-AT) in human brain tumors and to attempt to elucidate its significance. Seventy-seven consecutive unselected patients with various brain tumors were entered in this study. The α 1-AT and α 2-macroglobulin contents of the tumor extracts were qualitatively assessed by Ouchterlony immunodiffusion techniques. Plasminogen activator (PA) activity was assayed electrophoretically on sodium dodecyl sulfate gels. The patients were divided into two groups according to the positivity of their tumors to α 1-AT. Sixty-eight percent of the tumors were positive for α 1-AT, and all specimens were negative for α 2-macroglobulin. Clinical and biological parameters obtained in all study patients failed to show statistically significant differences between the two groups with the exception of PA activity (p = 0.001), the peritumoral edema as seen on computerized tomography, and the preoperative serum fibrinogen level. These three parameters were higher in the group with specimens positive to α 1-AT.

This study supports the hypothesis that α 1-AT is produced primarily by tumor cells in proportion to the regional proteolytic and inflammatory activity, and may protect the tumor cells.

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Norberto Andaluz and Mario Zuccarello

Object

The most appropriate treatment for cerebral aneurysms, both ruptured and unruptured, is currently under debate, and updated guidelines have yet to be defined. The authors attempted to identify trends in therapy for cerebral aneurysms in the US as well as outcomes.

Methods

The authors retrospectively reviewed data from the Nationwide Inpatient Sample hospital discharge database (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality) for the period 1993–2003. Multiple variables were categorized and subjected to statistical analysis for International Classification of Diseases, 9th Revision, Clinical Modification codes related to subarachnoid hemorrhage (SAH), unruptured aneurysm, and clipping and endovascular treatment of cerebral aneurysm.

Results

During the study period, the numbers of discharges remained stable for SAH but doubled for unruptured aneurysms. Concomitantly, the number of aneurysms treated with clip placement remained stable, and the number treated by means of endovascular procedures doubled. By the study's end, the mortality rates had decreased 20% for SAH and 50% for unruptured aneurysms. Increasing age was associated with increased mortality rates, mean length of hospital stay (LOS), and mean charges (p < 0.01). Endovascular treatment was used more often in older patients (p < 0.01). Teaching status and larger hospital size were associated with higher charges and longer hospital stays (although the association was not statistically significant) and with better outcomes (p < 0.05) and lower mortality rates (p < 0.05), especially in patients who underwent aneurysm clipping (p < 0.01). Endovascular treatment was associated with significantly higher mortality rates in small hospitals (p < 0.001) and steadily increasing morbidity rates (45%). Morbidity rates, mean LOS, and mean charges were higher for aneurysm clipping (p < 0.01).

Conclusions

From 1993 to 2003, endovascular techniques for aneurysm occlusion have been increasingly used, while the use of surgical clipping procedures has remained stable. Toward the end of the study period, better overall outcomes were observed in the treatment of cerebral aneurysms, both ruptured and unruptured. Large academic centers were associated with better results, particularly for surgical clip placement.

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Norberto Andaluz and Mario Zuccarello

Object

Recently updated guidelines failed to reflect significant progress in the treatment of intracerebral hemorrhage (ICH). Using data from a nationwide hospital database, the authors identified recent trends in therapy and outcomes for ICH, as well as the effect of associated comorbidities and procedures, including surgery.

Methods

Data from the Nationwide Inpatient Sample hospital discharge database (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality) for the period 1993–2005 was retrospectively reviewed. Multiple variables were categorized and subjected to statistical analysis for codes related to ICH from the International Classification of Diseases, 9th revision, Clinical Modification. Data linked by the Nationwide Inpatient Sample database to associated diagnoses and procedures were also retrieved and analyzed.

Results

The number of discharges remained constant for ICH. The mortality rate remained unchanged at an average of 31.6%, whereas routine discharges (home) steadily declined by 25%, and discharges other than home doubled (p < 0.01). By the end of the study, length of hospital stay decreased by 30% (p < 0.01), and mean hospital charges steadily increased to more than twice the original figures. Arterial hypertension was the most frequently associated comorbidity. Seizures were associated with longer hospital stays and higher mean hospital charges. Craniotomy was associated with decreased mortality rates but also with worse outcomes and lower rates of patients discharged home (p < 0.01). No geographic differences in treatment and outcomes were noted.

Conclusions

From 1993 to 2005, no significant progress in treatment and prevention of ICH was noted. There were no regional differences in the treatment and outcome of ICH. The role of surgery for ICH remains uncertain, and large-scale controlled studies are greatly needed to clarify this role.

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Norberto Andaluz, Mario Zuccarello and Charles Kuntz IV

Object

Few data exist regarding long-term outcomes after cervical corpectomy for spondylotic cervical myelopathy and radiculomyelopathy. In this retrospective review, long-term radiographic outcomes are reported for 130 patients after 1- or 2-level cervical corpectomy for spondylotic myelopathy or radiculomyelopathy.

Methods

Electronic medical records including clinical data and radiographic images during a 15-year period (1993–2008) were reviewed at the Cincinnati Department of Veterans Affairs Medical Center. All patients underwent radiographic follow-up for at least 12 months (range 12–156, mean 45 ± 39.3 months), as well as clinical follow-up performed by neurosurgery staff for a mean of 29.3 ± 39.6 months (range 4–156 months). Clinical parameters at surgery and last examination included the Chiles modified Japanese Orthopaedic Association (mJOA) Myelopathy Scale. Measurements included cervical spine sagittal alignment on lateral radiographs preoperatively and postoperatively, focal Cobb angles at operated levels, and C2–7 regional alignment. Statistical analysis included the Student t-test and chi-square test. Perioperative complications and additional surgery in the cervical spine were recorded.

Results

The mJOA scores improved from a mean of 11.91 ± 2.4 preoperatively to 14.9 ± 2.33 postoperatively. The mean sagittal lordosis of the C2–7 spine increased from −16.2° ± 9.2° preoperatively to −18.5° ± 11.9° at last follow-up. Focal Cobb angles averaged a slight kyphotic angulation of 4.1° ± 2.3° at latest radiographic follow-up; of note, 7 patients (5.4%), all who had cylindrical titanium mesh cages (CTMCs), showed severe kyphotic angulation (+8.4° ± 2.4°). Patients with preoperative myelopathy showed clinical improvement at follow-up. The fusion rate was 96.2%; 3 of the 5 patients with radiographic evidence of nonfusion were smokers. Patients with postoperative kyphosis had significantly more chronic neck pain (visual analog scale score >4 lasting more than 6 months) and visits related to pain (p <0.01). Those with CTMCs had higher rates of postoperative kyphosis, chronic neck pain, and visits related to pain, irrespective of the number of levels fused (p <001). At latest follow-up, although a kyphotic increase occurred in the focal cervical sagittal Cobb angles, lordosis increased in C2–7 sagittal Gore angles. Two patients (1.5%) underwent revision of the implanted graft and/or hardware, and 5 patients (3.8%) had another procedure for adjacent-level pathologies 1–9 years later (mean 4.4 ± 2.7 years).

Conclusions

Long-term follow-up data in our veteran population support cervical corpectomy as an effective, long-lasting treatment for spondylotic myelopathy of the cervical spine. Use of CTMCs without end caps was associated with statistically significant increased postoperative kyphotic angulation and chronic pain. Despite an increase in focal kyphosis over time, regional cervical sagittal lordotic alignment had increased at the latest follow-up. Further investigation will include the association of chronic neck pain and postoperative kyphosis, and high fusion rates among a veteran population of heavy smokers.

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Mario Zuccarello, Raymond Sawaya, Robert Lukin and Gabrielle deCourten-Myers

✓ A 24-year-old man developed a spontaneous cerebellar hematoma 5 years after the implantation of cerebellar electrodes. No vascular malformations were found either intraoperatively or radiographically. The histopathological findings of the cerebellar tissue obtained at biopsy from the region surrounding the electrodes support the hypothesis of a causal relationship between the spontaneous cerebellar hemorrhage and chronic cerebellar stimulation.

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Editorial

Cervical myelopathy

Vincent C. Traynelis

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Mario Zuccarello, Giovanni B. Soattin, Adam I. Lewis, Volker Breu, Hussein Hallak and Robert M. Rapoport

✓ The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET)A/B receptor antagonist Ro 47-0203, 4-tert-butyl-N-[6-(hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2′-bipyrimidin-4-yl]-benzenesulfonamide (bosentan), and the ETA receptor antagonist 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy-phenyl)-4-oxobut-2-enoic acid monosodium salt (PD155080), in the prevention of subarachnoid hemorrhage (SAH)—induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% of control as determined by angiography. Oral bosentan and PD155080 administration after the initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155080 levels were consistent with concentrations reported to inhibit ET-1 constriction of blood vessels in vitro. These results support the use of oral administration of ETA/B and ETA receptor antagonists as potential specific treatment for vasospasm resulting from SAH in humans.

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Hasan Kocaeli, Norberto Andaluz, Ondrej Choutka and Mario Zuccarello

✓Cerebral revascularization procedures have been used in the clinical management of actual or threatened cerebral ischemic states and unclippable cerebral aneurysms. An alternative to a low-flow bypass graft (for example, with the superficial temporal artery) is the use of high-flow grafts created using the saphenous vein (SV) or radial artery (RA). These high-flow grafts are particularly useful when otherwise adequate collateral flow is insufficient to enable sacrifice of the parent vessel without the risk of cerebral ischemia. In their clinical series of 13 patients who underwent high-flow bypass with an RA graft, the authors describe 8 women and 5 men whose ages ranged from 44 to 69 years (mean 57.84 ± 9.05 years). Indications for RA graft bypass were unclippable aneurysms in 10 patients and occlusive cerebrovascular disease in 3 patients. The authors review the properties of the 2 most common conduits, the SV and RA grafts. They present the technique of high-flow extracranial–intracranial bypass produced using RA grafts in the management of occlusive atherosclerotic disease and complex intracranial aneurysms that are not otherwise amenable to either clip ligation or coil occlusion.

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Mario Zuccarello, Jeffery T. Marsch, Gerald Schmitt, James Woodward and Douglas K. Anderson

✓ The purpose of this study was to use a new 21-aminosteroid (U-74006F) with in vitro antioxidant and antilipolytic properties as a pharmacological probe to assess the role of lipid hydrolysis and peroxidation in a rabbit model of subarachnoid hemorrhage (SAH)-induced vasospasm. Cerebral angiograms were performed on 15 rabbits. Eighteen hours later, 1 cc/kg of autologous blood was infused into the cisterna magna of all 15 animals. Six rabbits received no treatment, six received U-74006F starting 30 minutes after SAH, and three rabbits received the vehicle for U-74006F starting 30 minutes after SAH. At 72 hours post-SAH, a second angiogram was obtained. Digital subtraction angiographic techniques were used to measure the diameter of and contrast material flow through the basilar artery. At 72 hours post-SAH, vasospasm was evident in all untreated and vehicle-treated rabbits. The diameter of and the flow through the basilar artery were significantly reduced 42.3% ± 6.6% and 46.8% ± 5.8%, respectively, below pre-SAH levels (means ± standard error of the means). Treatment with U-74006F eliminated the SAH-induced vasospasm; in treated animals, both the flow through and the diameter of the basilar arteries were at pre-SAH levels. These findings indicate that: 1) membrane lipid changes (that is, hydrolysis with eicosanoid production and/or peroxidation) contribute to the chronic vasospasm resulting from SAH, and 2) U-74006F prevents the SAH-induced chronic vasospasm in this model by limiting these pathological membrane events.

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Ralph Rahme, Mario Zuccarello, Dawn Kleindorfer, Opeolu M. Adeoye and Andrew J. Ringer

Object

Although decompressive hemicraniectomy has been shown to reduce death and improve functional outcome following malignant middle cerebral artery territory infarction, there is ongoing debate as to whether surgery should be routinely performed, considering the very high rates of disability and functional dependence in survivors. Through a systematic review of the literature, the authors sought to determine the outcome from a patient's perspective.

Methods

In September 2010, a MEDLINE search of the English-language literature was performed using various combinations of 12 key words. A total of 16 papers were reviewed and individual study data were extracted.

Results

There was significant variability in study design, patient eligibility criteria, timing of surgery, and methods of outcome assessment. There were 382 patients (59% male, 41% female) with a mean age of 50 years, 25% with dominant-hemisphere infarction. The mortality rate was 24% and the mean follow-up in survivors was 19 months (range 3–114 months). Of 156 survivors with available modified Rankin Scale (mRS) scores, 41% had favorable functional outcome (mRS Score ≤ 3), whereas 47% had moderately severe disability (mRS Score 4). Among 157 survivors with quality of life assessment, the mean overall reduction was 45%: 67% for physical aspect and 37% for psychosocial aspect. Of 114 screened survivors, depression affected 56% and was moderate or severe in 25%. Most patients and/or caregivers (77% of the 209 interviewed) were satisfied and would give consent again for the procedure.

Conclusions

Despite high rates of physical disability and depression, the vast majority of patients are satisfied with life and do not regret having undergone surgery.