Edward A. M. Duckworth

NF-κB protects neurons from ischemic injury after middle cerebral artery occlusion in mice

Knowledge about the molecular mechanisms of neuronal survival following ischemia is crucial to the development of therapeutic interventions for victims of stroke. Previous research in our laboratory has implicated nuclear factor-kappaB (NF-kappaB) as contributing to neuronal survival in response to toxic or ischemic brain insult, with in vivo models having focused on the rat. To take advantage of genetic alterations available in the mouse, we utilized a murine transient endovascular middle cerebral artery occlusion (MCAO) model to examine the influence of NF-kappaB on neuronal survival. When brains were immunostained for the nuclear localization sequence (NLS) of the p50 subunit of NF-kappaB, a unilateral increase in immunoreactivity was seen, especially in pyramidal cell layers of the ipsilateral (stroked) hippocampus. When transgenic mice lacking p50 were compared with non-transgenic counterparts using Fluoro-Jade, a marker for neurodegeneration, both the hippocampus and striatum showed enhanced neurodegeneration at various survival times after 1 h of MCAO. In the hippocampus specifically, there was an eightfold increase in Fluoro-jade staining in the p50 knockout group vs. the non-transgenic group. Sections double stained for Fluoro-Jade and NF-kappaB activity (using a mouse engineered with a NF-kappaB responsive promoter driving a LacZ gene to produce beta galactosidase) demonstrated neuronal degeneration only in regions sparsely showing NF-kappaB activity, and those demonstrating NF-kappaB activity failed to degenerate. These data provide evidence that NF-kappaB participates in survival signaling following temporary focal ischemia, and thus may represent an attractive target for pharmacologic activation in the treatment of stroke.

Temporary focal ischemia in the mouse: Technical aspects and patterns of Fluoro-Jade evident neurodegeneration

Animal models of cerebral infarction are crucial to understanding the mechanisms of neuronal survival following ischemic brain injury and to the development of therapeutic interventions for victims of all types of stroke. Rodents have been used extensively in such research. One rodent model of stroke utilizes either permanent or temporary occlusion of the middle cerebral artery (MCAO) to produce ischemia. Since the development of an endovascular method for this was published in 1989, MCAO has been applied commonly to the rat, and often paired with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining for stroke volume measurement. Meanwhile, advances in the ability to genetically alter mice have allowed exciting lines of research into ischemia. Because of technical demands and issues with survival, relatively few laboratories have investigated the MCAO method in the mouse. Our present work utilizes a mouse middle cerebral occlusion (MCAO) model of embolic stroke to study neuronal degeneration following temporary focal cerebral ischemia. C57Bl/6J mice were used to examine the exact effects of MCAO using Fluoro-Jade, a marker of neurodegeneration that allows observation of specific brain regions and cells destined to die. A time course of escalating neuronal degeneration from 10 min to 7 days following MCAO was established. Technical aspects of this popular method for transient focal ischemia as it applies to the mouse are discussed.

Comparison between anterior cervical discectomy fusion and cervical corpectomy fusion using titanium cages for reconstruction: analysis of outcome and long-term follow-up

Retrospective comparative study of 80 consecutive patients treated with either anterior cervical discectomy fusion (ACDF) or anterior cervical corpectomy fusion (ACCF) for multi-level cervical spondylosis. To compare clinical outcome, fusion rates, and complications of anterior cervical reconstruction of multi-level ACDF and single-/multi-level ACCF performed using titanium mesh cages (TMCs) filled with autograft and anterior cervical plates (ACPs). Reconstruction of the cervical spine after discectomy or corpectomy with titanium cages filled with autograft has become an acceptable alternative to both allograft and autograft; however, there is no data comparing the outcome of multi-level ACDF and single-/multi-level ACCF using this reconstruction. We evaluated 80 consecutive patients who underwent surgery for the treatment of multi-level cervical spondylosis at our institution from 1998 to 2001. In this series, 42 patients underwent multi-level ACDF (Group 1) and 38 patients underwent ACCF (Group 2). Interbody TMCs and local autograft bone with ACPs were used in both procedures. Medical records were reviewed to assess outcome. Clinical outcome was measured by Odom’s criteria. Operative time and blood loss were noted. Radiographs were obtained at 6 and 12xa0weeks, 6xa0months, 1xa0year, and 2xa0years (if necessary). Early hardware failures and pseudarthroses were noted. Cervical sagittal curvature was measured by Ishihara’s index at 1xa0year. Group 1 had a mean age 46.2xa0years (range 35–60xa0years). Group 2 had a mean age 50.1xa0years (range 35–70xa0years).The operative time was significantly lower (Pxa0<xa00.001) and blood loss significantly higher (Pxa0<xa00.001) in Group 2 than in Group 1. At a minimum of 1xa0year follow up, patients in both groups had equivalent improvement in their clinical symptoms. The fusion rates for Group 1 were 97.6 and 92.1% for Group 2. The rates of early hardware failure were higher in Group 2 (2.6%) than in Group 1 (0%). The fusion rates for Group 1 were not significantly higher than Group 2 (Pxa0>xa00.28). There was one patient in Group 1 and 2 patients in Group 2 with pseudarthroses. Complication rates in Group 2 were not significantly higher (Pxa0>xa00.341). Cervical lordosis was well-maintained (80%) in both groups. Both multi-level ACDF and ACCF with anterior cervical reconstruction using TMC filled with autograft and ACP for treatment of multi-level cervical spondylosis have high fusion rates and good clinical outcome. However, there is a higher rate of early hardware failure and pseudarthroses after ACCF than ACDF. Hence, in the absence of specific pathology requiring removal of vertebral body, multi-level ACDF using interbody cages and autologous bone graft could result in lower morbidity.

Trephine epilepsy surgery: the inferior temporal gyrus approach.

OBJECTIVEnTo describe our technique for temporal lobe epilepsy surgery using a minimal-access approach.nnnMETHODSnOur epilepsy surgery registry was reviewed, and all patients with at least 2 years follow-up were queried. Clinical data included age, sex, side of lesion, presence of mesial temporal sclerosis, surgical complications, and Engel class outcome. Our operation was performed through a 6- to 8-cm linear vertical incision extending upward from just anterior to the tragus. An oval trephine (2 x 3 cm) craniotomy was performed flush with the middle fossa floor. Resection of part of the inferior temporal gyrus provided a corridor to the mesial temporal lobe. Identification of the temporal horn of the lateral ventricle was followed by resection of the parahippocampal gyrus, the amygdala, and the uncus. Segregation of the hippocampus and its subsequent resection in subpial fashion preserved perimesencephalic vasculature. Use of a fine suture for skin closure produced a cosmetic result.nnnRESULTSnIn our 8-year series of 201 patients with a minimum follow-up duration of 2 years, we have observed a low number (1.5%) of complications and a 78% rate of Engel Class I seizure-free outcome. Surgery times were short (average, 2-5 h; range, 2 h 20 min-4 h 10 min) and hospital stays brief (<3 d; range, 1-4 d).nnnCONCLUSIONnOur results suggest that the trephine craniotomy with the inferior temporal gyrus approach has the advantage of minimal invasiveness, including brief operative times and postoperative stays, and also effectively reduces or eradicates medically intractable seizures.

Rats receiving systemic 3-nitropropionic acid demonstrate impairment of memory in Morris water maze

A recent hypothesis for the etiology of Huntingtons disease (HD) postulates that impaired mitochondrial energy production and/or the presence of reactive free radical species may lead to slow excitotoxic neuronal death. Consistent with this hypothesis, systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats produces selective striatal neuropathology mimicking that seen in HD. Such injections of 3-NP additionally produce motor changes thought to model HD, but possible cognitive changes have not been well described. The present study explores this issue. Sixteen rats underwent acquisition training and subsequent memory assessment in a Morris water maze apparatus. Training over 5 consecutive days consisted of trials during which each rat could escape swimming by finding a permanently located submerged platform. Following training, the rats were divided into two groups and received daily intraperitoneal injections of either 3-NP (15 mg/kg) or saline vehicle for 7 days. On Day 8, a retention trial was conducted, in which the platform was removed and the rats were allowed to swim for 2 min. Swimming patterns were tracked and recorded. The rats receiving 3-NP had impaired memory of the platform location, as represented by decreased time swimming over the platform area, fewer entries into the area, and longer latency to entering the area. These results suggest that the 3-NP rat model produces cognitive dysfunctions that parallel HD dementia.

Completion angiography for surgically treated cerebral aneurysms: An economic analysis - Commentary

OBJECTIVETo compare cost-effectiveness of different strategies for completion angiography after cerebral aneurysm clipping. METHODSA literature search was used to determine the outcome probabilities and costs of various strategies. The pooled results were used in a Markov cost-effectiveness model to compare quality-adjusted life-years and costs of each strategy. Sensitivity (threshold) analyses and Monte Carlo simulation were used to test variation in the model. RESULTSRoutine (for all cases) intraoperative angiography proved to be slightly more cost-effective than selective (only for cases deemed “high risk”) intraoperative angiography, being both less costly and more effective. Routine postoperative angiography was the least cost-effective. However, in centers whose rates of clip-induced arterial compromise are much lower than the averages reported in the literature, selective angiography might be warranted. CONCLUSIONRoutine intraoperative angiography remains the most cost-effective form of completion angiography after aneurysm clipping, at least at our present state of technology.

Double-barrel bypass for cerebral ischemia: technique, rationale, and preliminary experience with 10 consecutive cases.

BACKGROUND: In selected patients, extracranial-intracranial bypass remains an important treatment for the prevention of stroke. Traditionally, superficial temporal artery–middle cerebral artery (STA-MCA) bypass uses 1 STA branch. We have adopted a “double-barrel” technique in which both branches are joined with MCA recipients in distinct vascular territories. OBJECTIVE: To assess the feasibility of routinely using both branches of the STA for cerebral revascularization. METHODS: Ten consecutive patients underwent double-barrel bypass. Patients were selected if they demonstrated symptomatic MCA hypoperfusion resistant to medical therapy or had symptomatic moyamoya disease. Flow-directed bypass was performed to augment flow to the territories most at risk in each case, based on preoperative and intraoperative data. Computed tomography perfusion was routinely performed to evaluate baseline deficits and postoperative augmentation. Clinical data were analyzed to assess patient demographics and outcomes. RESULTS: The double-barrel bypass was no more difficult technically than the traditional approach, with the second branch harvested through a small satellite incision. By isolating temporary occlusion to each territory, there was no additional ischemia to each brain region. No intraoperative complications or wound-healing issues occurred. Postoperative computed tomography perfusion studies all showed improvement, and delayed vascular imaging demonstrated universal graft patency. Nine of 10 patients have been asymptomatic since surgery, whereas 1 patient demonstrated symptoms in a separate vascular distribution. CONCLUSION: Double-barrel STA-MCA bypass is both feasible and potentially advantageous. In our series, both bypass branches remained patent, augmenting flow to the territories most at need. ABBREVIATIONS: CTP, computed tomography perfusion ICA, internal carotid artery ICG, indocyanine green MMA, middle meningeal artery STA-MCA, superficial temporal artery–middle cerebral artery TIA, transient ischemic attack

The 1-piece transbasal approach: operative technique and anatomical study

OBJECTnThe transbasal approach (TBA) is an anterior skull base approach, which provides access to the anterior skull base, sellar-suprasellar region, and clivus. The TBA typically involves a bifrontal craniotomy with orbital bar and/or nasal bone osteotomies performed in 2 separate steps. The authors explored the feasibility of routinely performing this approach in 1 piece with a quantitative cadaveric anatomical study, and present an operative case example of their approach.nnnMETHODSnSeven latex-injected cadaveric heads underwent a 1-piece TBA, followed by additional bone removal typical for a traditional 2-piece approach. Six surgical angles relative to the pituitary stalk, as well as the surface area of the orbital roof osteotomy, were measured before and after additional bone removal. The vertical angle from the frontonasal suture to the foramen cecum was measured in all specimens. In addition to an anatomical study, the authors have used this technique in the operating room, and present an illustrative case of resection of an anterior skull base meningioma.nnnRESULTSnMorphometric results were as follows: the vertical angle from the frontonasal suture to the foramen cecum ranged from 17.4° to 29.7° (mean 23.8° ± 4.8°) superiorly. Of the 6 surgical angle measures, only the middle horizontal angle was increased in the 2-piece versus the 1-piece approach (mean 43.4° ± 4.6° vs 43.0° ± 4.3°, respectively; p = 0.049), with a mean increase of 0.4°. The surface area of the orbital osteotomy was increased in the 2-piece versus the 1-piece approach (mean 2467 mm(2) ± 360 mm(2) vs 2045 mm(2) ± 352 mm(2), respectively; p < 0.001). The patient in the illustrative clinical case had a good outcome, both clinically and cosmetically.nnnCONCLUSIONSnThe 1-piece TBA provides an alternative to the traditional 2-piece approach. It allows easier reconstruction, potentially decreased operative time, and improved cosmesis. While more of the orbital roof can be removed with the 2-piece approach, this additional bone removal offers only a small increase in 1 of 6 surgical angles that were measured.

Management of infections complicating the orbitocranial approaches: Report of two cases and review of literature

Background: The orbitocranial approaches are now indispensible for treating lesions of the skull base, providing access to lesions in the anterior and middle cranial fossae, as well as the upper clivus and anterior brainstem. The management of infectious complications of the orbitocranial approaches, however, has evaded the literature. Case Description: We present two cases of patients who underwent orbitocranial approach whose clinical course was complicated by wound infection and osteomyelitis. One patient was treated with antibiotics and then had a custom implant placed for cranioplasty. The other case was managed with removal of bone and wire-mesh cranioplasty. Conclusion: Management of orbitocraniotomy infections can be difficult due to the complex geometry of the flap and to cosmetic considerations. Once the infection involves the bone, the bone can be replaced after cleaning or discarded and a cranioplasty performed. Cranioplasty can be performed with wire-mesh or a custom implant made by computer-assisted modeling.

Microvascular decompression of a C-2 segmental-type vertebral artery producing trigeminal hypesthesia

The authors report a case of trigeminal hypesthesia caused by compression of the spinal cord by a C-2 segmental-type vertebral artery (VA) that was successfully treated with microvascular decompression. Aberrant intradural VA loops have been reported as causes of cervical myelopathy, some of which improved with microvascular decompression. A 52-year-old man presented with progressive complaints of headache, dizziness, left facial numbness, and left upper-extremity paresthesia that worsened when turning his head to the right. Magnetic resonance imaging of the cervical spine showed the left VA passing intradurally between the axis and atlas, foregoing the C-1 foramen transversarium, and impinging on the spinal cord. The patient underwent left C-1 and C-2 hemilaminectomies followed by microvascular decompression of an aberrant VA loop compressing the spinal cord. The patient subsequently reported complete resolution of symptoms.