Search

Essential fatty acids (EFA) play a critical role in the brain and regulate many of the processes altered in Alzheimer's disease (AD). Technical advances are allowing for the dissection of complex lipid pathways in normal and diseased states. Arachidonic acid (AA) and specific isoforms of phospholipase A2 (PLA2) appear to be critical mediators in amyloid-β (Aβ)-induced pathogenesis, leading to learning, memory, and behavioral impairments in mouse models of AD. These findings and ongoing research into lipid biology in AD and related disorders promise to reveal new pharmacological targets that may lead to better treatments for these devastating conditions.

Young age is considered an important factor in determining outcomes after microsurgical resection of arteriovenous malformations (AVMs), but better results in children have not been adequately explained. A consecutive series of pediatric and adult patients was reviewed to determine whether differences in outcomes between these two groups were due to differences in AVM anatomy, rupture rates, neurological condition at presentation, treatment techniques, or other causes.As assessed using the modified Rankin Scale (mRS), patient characteristics, clinical presentation, AVM anatomy, treatment techniques, and outcomes were compared between age groups. Thirty-two pediatric and 192 adult patients underwent microsurgical AVM resection during a 6.4-year period; complete resection was achieved in 97% of the children and 98% of adults. Superior outcomes were observed in children, who had better final mRS scores (p = 0.003) and more favorable changes in these scores (the condition of 94% of children improved or remained unchanged, compared with 70% of adults; p = 0.001). The change in the mean mRS scores was 1.31 for children and 0.14 for adults (p = 0.001). There were no significant clinical, anatomical, or therapeutic differences between children and adults.This analysis confirms the observation that children fare better than adults after microsurgical AVM resection. This discrepancy cannot be explained by differences in AVM anatomy, lesion rupture rates, presenting neurological condition, or treatment techniques, leading the authors to infer that neural plasticity may augment surgical tolerance and recovery in children. These findings bolster the choice of aggressive microsurgical management of AVMs and recalibration of surgical risk assessment in children.

Malignant subfrontal (olfactory) peripheral nerve sheath tumors (MPNSTs) are exceedingly rare. Although meningiomas are the most common subfrontal extra-axial lesions, it is important to recognize that MPNSTs, which are radiographically similar to meningiomas, can also be present in this location. MPNSTs require more aggressive surgical and postoperative management than meningiomas. In this paper, we describe a patient with a subfrontal MPNST with unusual histological characteristics and present a review of the literature. A 49-year-old woman presented with chronic sinusitis and progressive headaches. A neurological examination revealed left-sided anosmia. Brain-imaging studies revealed a large left subfrontal mass with extension into the frontal and ethmoid sinuses and the nasal cavity. The patient underwent both a bifrontal transbasal craniotomy and a transnasal approach for an attempt at total resection of both the intradural and extradural components of the MPNST. The patient was treated postoperatively with radiation therapy, and had no evidence of recurrence at her follow-up examination 1-year after treatment. Subfrontal PNSTs are extremely rare and usually benign. The specific cell and nerve of origin for these tumors remains unknown. Our case shows that these rare lesions can present as a malignant variant and thus require aggressive surgical and postoperative management to provide long-term tumor control.

Object Trigeminal neuralgia (TN) is characterized by paroxysmal lancinating pain in the trigeminal nerve distribution. When TN is refractory to medical management, patients are referred for microvascular decompression (MVD), radiofrequency ablation, or radiosurgery. After the initial treatment, patients may have refractory or recurrent symptoms requiring retreatment. The purpose of this study was to determine what factors are associated with the need for retreatment and which modality is most effective. Methods To define this population further, the authors evaluated a cohort of patients who required retreatment for TN. The mean follow-up periods were 51 months from the first treatment and 23 months from the last one, and these were comparable among treatment groups. Conclusions Trigeminal neuralgia can recur after neurosurgical treatment. In this study the authors demonstrate that the number of patients requiring retreatment is not negligible. Lower retreatment rates were seen in patients who initially underwent radiosurgery, compared with those in whom MVD or radiofrequency ablation were performed. Radiosurgery was more likely to be the final treatment for recurrent TN regardless of the initial treatment. After retreatment, the majority of patients attained complete or very good pain relief. Pain relief after retreatment correlates with postoperative facial numbness.

Object Trigeminal neuralgia (TN) is a painful disorder that frequently causes lancinating, electrical shock–like pain in the trigeminal distribution. Common surgical treatments include microvascular decompression (MVD), radio-surgery, and radiofrequency ablation, and complete pain relief is generally achieved with a single treatment in 70 to 85% of cases for all modalities. In a subset of patients with multiple sclerosis (MS), however, the rates of surgical treatment failure and the need for additional procedures are significantly increased compared with those in patients without MS. In this study the authors report their experience with a cohort of 11 patients with TN who also had MS, and assess the efficacy of MVD, gamma knife surgery (GKS), and radiofrequency ablation in achieving complete or partial long-term pain relief. Methods Eleven patients with TN and MS who were treated by the senior author (N.B.) at the University of California, San Francisco were included in this study. All patients underwent GKS and/or radiofrequency ablation, and four received MVD. A detailed clinical history and intraoperative findings were recorded for each patient and frequent follow-up evaluations were performed, with a mean follow-up duration of 40.6 months (range 1–96 months). Pain was assessed for each patient by using the Barrow Neurological Institute scale (Scores I–V). Conclusions Achieving complete pain relief in patients with TN and MS required significantly more treatments compared with all other patients with TN who did not have MS (p = 0.004). Even when compared with a group of 32 patients who had highly refractory TN, the cohort with MS required significantly more treatments (p = 0.05). Radiosurgery proved to be an effective procedure and resulted in fewer retreatments and longer pain-free intervals compared with MVD or radiofrequency ablation.

Object Cerebral autoregulation may be altered after traumatic brain injury (TBI). Recent evidence suggests that patients' autoregulatory status following severe TBI may influence cerebral perfusion pressure management. The authors evaluated the utility of incorporating a recently upgraded parenchymal thermal diffusion probe for the measurement of cerebral blood flow (CBF) in the neurointensive care unit for assessing cerebral autoregulation and vasoreactivity at bedside. Methods The authors evaluated 20 patients with severe TBI admitted to San Francisco General Hospital who underwent advanced neuromonitoring. Patients had a parenchymal thermal diffusion probe placed for continuous bedside monitoring of local CBF (locCBF) in addition to the standard intracranial pressure and brain tissue oxygen tension (PbtO2) monitoring. The CBF probes were placed in the white matter using a separate cranial bolt. A pressure challenge, whereby mean arterial pressure (MAP) was increased by about 10 mm Hg, was performed in all patients to assess autoregulation. Cerebral CO2 vasoreactivity was assessed with a hyperventilation challenge. Local cerebral vascular resistance (locCVR) was calculated by dividing cerebral perfusion pressure by locCBF. Local cerebral vascular resistance normalized to baseline (locCVRnormalized) was also calculated for the MAP and hyperventilation challenges. Results In all cases, bedside measurement of locCBF using a cranial bolt in patients with severe TBI resulted in correct placement in the white matter with a low rate of complications. Mean locCBF decreased substantially with hyperventilation challenge (−7 ± 8 ml/100 g/min, p = 0.0002) and increased slightly with MAP challenge (1 ± 7 ml/100 g/min, p = 0.17). Measurements of locCBF following MAP and hyperventilation challenges can be used to calculate locCVR. In 83% of cases, locCVR increased during a hyperventilation challenge (mean change +3.5 ± 3.8 mm Hg/ml/100 g/min, p = 0.0002), indicating preserved cerebral CO2 vasoreactivity. In contrast, we observed a more variable response of locCVR to MAP challenge, with increased locCVR in only 53% of cases during a MAP challenge (mean change −0.17 ± 3.9 mm Hg/ml/100 g/min, p = 0.64) indicating that in many cases autoregulation was impaired following severe TBI. Conclusions Use of the Hemedex thermal diffusion probe appears to be a safe and feasible method that enables continuous monitoring of CBF at the bedside. Cerebral autoregulation and CO2 vasoreactivity can be assessed in patients with severe TBI using the CBF probe by calculating locCVR in response to MAP and hyperventilation challenges. Determining whether CVR increases or decreases with a MAP challenge (locCVRnormalized) may be a simple provocative test to determine patients' autoregulatory status following severe TBI and helping to optimize CPP management.

OBJECTIVE Stereotactic radiosurgery makes brain arteriovenous malformations (AVM) more manageable during their microsurgical resection. To better characterize these effects, we compared results of microsurgical resection of radiated (RS) and nonradiated (RS) AVMs to demonstrate that previous radiosurgery facilitates surgery and decreases operative morbidity. METHODS From our series of 344 patients who underwent AVM resections at the University of California, San Francisco (1997-2007), 21 RS patients were matched with 21 RS patients based on pretreatment clinical and AVM characteristics. Matching was blinded to outcomes, which were assessed with the modified Rankin Scale. RESULTS Mean AVM volume was reduced by 78% (P < 0.01), and Spetzler-Martin grades were reduced in 52% of RS patients (P < 0.001). Preoperative embolization was used less in RS than in RS patients (P < 0.001). Mean operative time (P < 0.01), blood loss (P < 0.05), and length of hospital stay (P < 0.05) were lower in the RS group. Surgical morbidity was 14% higher in RS patients, and they demonstrated significant worsening in modified Rankin Scale scores after surgery, whereas RS patients did not (P < 0.01). RS patients deteriorated between AVM diagnosis and surgery owing to hemorrhages during the latency period (P < 0.05). CONCLUSION Previous radiosurgery facilitates AVM microsurgery and decreases operative morbidity. Radiosurgery is recommended for unruptured AVMs that are not favorable for microsurgical resection. Microsurgical resection is recommended for radiated AVMs that are not completely obliterated after the 3-year latency period but are altered favorably for surgery, even in asymptomatic patients. Prompt resection of persistent AVMs should be considered to avoid the risk of postlatency hemorrhage and to optimize patient outcomes.

Neuronal expression of familial Alzheimer's disease-mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-beta (Abeta) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer's disease pathogenesis is uncertain. We used a lipidomics approach to generate a broad profile of fatty acids in brain tissues of hAPP-expressing mice and found an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A(2) (GIVA-PLA(2)). The levels of activated GIVA-PLA(2) in the hippocampus were increased in individuals with Alzheimer's disease and in hAPP mice. Abeta caused a dose-dependent increase in GIVA-PLA(2) phosphorylation in neuronal cultures. Inhibition of GIVA-PLA(2) diminished Abeta-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA(2) protected hAPP mice against Abeta-dependent deficits in learning and memory, behavioral alterations and premature mortality. Inhibition of GIVA-PLA(2) may be beneficial in the treatment and prevention of Alzheimer's disease.

Objective Tentorial dural arteriovenous fistulae (DAVF) are rare, have a high risk of hemorrhage, often cannot be obliterated endovascularly, and frequently require microsurgical interruption of the draining vein. We differentiated these fistulae into six types and developed specific operative strategies on the basis of these types. Methods During a 9-year period, 31 patients underwent microsurgical treatment for tentorial fistulae: seven galenic DAVF, eight straight sinus DAVF, three torcular DAVF, three tentorial sinus DAVF, eight superior petrosal sinus DAVF, and two incisural DAVF. Results The posterior interhemispheric approach was used with galenic DAVF; the supracerebellar-infratentorial approach was used with straight sinus DAVF; a torcular craniotomy was used with torcular DAVF; the supratentorial-infraoccipital approach was used with tentorial sinus DAVF; the extended retrosigmoid approach was used with superior petrosal sinus DAVF; and a pterional or subtemporal approach was used with incisural DAVF. Angiographically, 94% of the fistulae were obliterated completely. Four patients had transient neurological morbidity, none had permanent neurological morbidity; and there was no operative mortality (mean follow-up, 4.2 yr). Conclusion Tentorial DAVF can be differentiated on the basis of fistula location, dural base, associated sinus, and direction of venous drainage. The operative strategy for each type is almost algorithmic, with each type having an optimum surgical approach and an optimum patient position that allows gravity to retract the brain, open subarachnoid planes, and shorten dissection times. No matter the type, the fistula is treated microsurgically by simple interruption of the draining vein.

✓Distal aneurysms of basilar perforating and circumferential arteries are exceedingly rare. The authors encountered one patient with a distal basilar perforating artery aneurysm and two with aneurysms arising from circumferential branches of the basilar artery (BA). The diagnostic features, microsurgical treatment, and outcomes in these three patients are described. The first patient, a 27-year-old man, presented with an angiogram-negative subarachnoid hemorrhage (SAH), and subsequent readmission for a new hemorrhage revealed a centrally thrombosed aneurysm arising from a basilar apex perforating artery. The second patient, a 68-year-old man, presented for follow-up evaluation 2 months after an angio-gram-negative SAH, and an aneurysm was identified on a circumferential artery originating from the BA trunk. The third patient, a 2-year-old boy, presented with blunt head trauma and a pseudoaneurysm arising from a basilar apex circumferential artery. All three aneurysms were managed microsurgically with aneurysm trapping, via either an orbitozygomatic or an extended retrosigmoid approach. Occlusion of the distal perforating or circumferential artery was well tolerated in all cases, with no neurological sequelae resulting from surgery. Features common to all three aneurysms were dolichoectatic morphology, intraluminal thrombus, and SAH. These aneurysms may be difficult to diagnose given their small size and delayed filling on angiographic studies. Consequently, their presence in cases of angiogram-negative SAH may be underestimated. These aneurysms are not amenable to endovascular treatment, but excellent results can be obtained with microsurgical exposure and trapping.

Circumferential cervical decompression and fusion (CCDF) is an important technique for treating patients with severe cervical myelopathy. While circumferential cervical decompression and fusion may provide improved spinal cord decompression and stability compared to unilateral techniques, it is commonly associated with increased morbidity and mortality. We performed a retrospective analysis of patients undergoing CCDF at the University of California, San Francisco (UCSF) between January 2003 and December 2004. We identified 53 patients and reviewed their medical records to determine the effectiveness of CCDF for improving myelopathy, pain, and neurological function. Degree of fusion, functional anatomic alignment, and stability were also assessed. Operative morbidity and mortality were measured. The most common causes of cervical myelopathy, instability, or deformity were degenerative disease (57%) and traumatic injury (34%). Approximately one-fifth of patients had a prior fusion performed elsewhere and presented with fusion failure or adjacent-level degeneration. Postoperatively, all patients had stable (22.6%) or improved (77.4%) Nurick grades. The average preoperative and postoperative Nurick grades were 2.1 +/- 1.9 and 0.4 +/- 0.9, respectively. Pain improved in 85% of patients. All patients had radiographic evidence of fusion at last follow-up. The most common complication was transient dysphagia. Our average clinical follow-up was 27.5 +/- 9.5 months. We present an extensive series of patients and demonstrate that cervical myelopathy can successfully be treated with CCDF with minimal operative morbidity. CCDF may provide more extensive decompression of the spinal cord and may be more structurally stable. Concerns regarding operation-associated morbidity should not strongly influence whether CCDF is performed.

✓Epithelioid angiosarcoma of bone is a rare, high-grade lesion that is highly vascular and can be associated with a bleeding diathesis. An association has been reported in angiosarcomas in other locations with coagulopathy from tumor-related disseminated intravascular coagulopathy and fibrinolysis. The authors report the case of a rare occurrence of a primary sacral epithelioid angiosarcoma associated with a large epidural hematoma and a severe bleeding diathesis. A 25-year-old woman presented with weakness, fatigue, neck and low-back pain, and progressive left S-1 radiculopathy. Imaging studies revealed a large ventral epidural hematoma extending from the sacral region rostrally to C-2 and a vascular tumor located in the sacrum. The patient underwent a sacral laminectomy, complicated by postoperative bleeding from the wound, and required massive transfusions. Ultimately, multimodal therapy was required to obtain hemostasis, including the use of endovascular embolization, radiation therapy, and an infusion of epsilon-aminocaproic acid with heparin. This case represents the first report of a primary epithelioid angiosarcoma in the sacrum and emphasizes that the coagulopathy seen in angiosarcoma is also a feature of this epithelioid variant.