David S. Xu

Natural history of brain arteriovenous malformations: a systematic review

OBJECT The authors aimed to systematically review the literature to clarify the natural history of brain arteriovenous malformations (BAVMs). METHODS The authors searched PubMed for one or more of the following terms: natural history, brain arteriovenous malformations, cerebral arteriovenous malformations, and risk of rupture. They included studies that reported annual rates of hemorrhage and that included either 100 patients or 5 years of treatment-free follow-up. RESULTS The incidence of BAVMs is 1.12-1.42 cases per 100,000 person-years; 38%-68% of new cases are first-ever hemorrhage. The overall annual rates of hemorrhage for patients with untreated BAVMs range from 2.10% to 4.12%. Consistently implicated in subsequent hemorrhage are initial hemorrhagic presentation, exclusively deep venous drainage, and deep and infrantentorial brain location. The risk for rupture seems to be increased by large nidus size and concurrent arterial aneurysms, although these factors have not been studied as thoroughly. Venous stenosis has not been implicated in increased risk for rupture. CONCLUSIONS For patients with BAVMs, although the overall risk for hemorrhage seems to be 2.10%-4.12% per year, calculating an accurate risk profile for decision making involves clinical attention and accounting for specific features of the malformation.

Proteomic identification of glutamine synthetase as a differential marker for oligodendrogliomas and astrocytomas

OBJECT Astrocytomas and oligodendrogliomas are primary CNS tumors that remain a challenge to differentiate histologically because of their morphological variability and because there is a lack of reliable differential diagnostic markers. To identify proteins that are differentially expressed between astrocytomas and oligodendrogliomas, the authors analyzed the proteomic expression patterns and identified uniquely expressed proteins in these neoplasms. METHODS Proteomes of astrocytomas and oligodendrogliomas were analyzed using 2D gel electrophoresis and subsequent computerized gel analysis to detect differentially expressed proteins. The proteins were identified using high-performance liquid chromatography accompanied by tandem mass spectrometry. To determine the role of the differentially expressed proteins in astrocytes, undifferentiated glial cell cultures were treated with dibutyryl-cyclic adenosine monophosphate (cAMP). RESULTS Two-dimensional gel electrophoresis revealed that glutamine synthetase was differentially expressed in astrocytomas and oligodendrogliomas. Western blot and immunohistochemical analyses confirmed the increased expression of glutamine synthetase in astrocytomas compared with oligodendrogliomas. Whereas glutamine synthetase expression was demonstrated across all grades of astrocytomas (Grade II-IV [15 tumors]) and oligoastrocytomas (4 tumors), it was expressed in only 1 oligodendroglioma (6% [16 tumors]). Treatment of undifferentiated glial cell cultures with dibutyryl-cAMP resulted in astrocyte differentiation that was associated with increased levels of glial fibrillary acidic protein and glutamine synthetase. CONCLUSIONS These data indicate that glutamine synthetase expression can be used to distinguish astrocytic from oligodendroglial tumors and may play a role in the pathogenesis of astrocytomas.

Adult presentation of a familial-associated vein of galen aneurysmal malformation: Case report

BACKGROUND AND IMPORTANCE: Vein of Galen aneurysmal malformations (VGAMs) arise from persistent arteriovenous shunting from primitive choroidal vessels into the median prosencephalic vein of Markowski, the embryonic precursor of the vein of Galen. VGAMs rarely present past infancy, and their natural history in adults is unknown. We report the first case of a familial-associated VGAM in an asymptomatic adult female patient. The clinical features of this case are presented alongside a systematic review of the literature on adult VGAM cases to assess the natural history, clinical management, and genetic basis of this rare neurovascular lesion. CLINICAL PRESENTATION: A previously healthy 44-year-old woman with a family history of a VGAM in a stillborn presented with an 8-week onset of dizziness and vertigo that spontaneously resolved. Time-resolved magnetic resonance angiography identified a choroidal VGAM. No intervention was undertaken at this time because of the patients asymptomatic status after 9 months of follow-up. CONCLUSION: Based on our review of the literature, this is the first case report of a familial-associated VGAM in an adult patient and suggests that VGAM development can be genetically linked. Of 15 adult VGAM cases previously reported, all patients were either symptomatic or treated, thus precluding determination of VGAM natural history in adults. Patient outcomes correlated with the severity of presenting symptoms, which ranged from asymptomatic to immediately life-threatening. We hypothesize that self-selection may render VGAMs to be more benign for them to persist past childhood. Further investigation of the molecular biology underlying VGAM development is warranted.

Delayed cranial nerve palsy after coiling of carotid cavernous sinus aneurysms: Case report

OBJECTIVEDetachable endovascular coils have become a common treatment strategy for carotid cavernous sinus aneurysms (CCAs), but previously unrecognized postprocedure complications may emerge as longer follow-up data are accumulated. In this report, the authors document the first known cases of delayed cranial neuropathy following CCA coiling in 3 patients, all of whom present at least a year postprocedure without aneurysm regrowth. The potential mechanisms underlying this syndrome are discussed as well as their implications on the selection and optimal endovascular management of CCA patients. CLINICAL PRESENTATIONThree previously healthy females aged 50, 60, and 62 underwent CCA coiling at our institution and subsequently developed ipsilateral cranial nerve palsies at 56, 28, and 14 months, respectively, post-procedure. At presentation, all 3 patients had a new, recurrent area of flow in their CCA without changes in aneurysm size. INTERVENTIONOne patient declined further treatment. In the other 2 patients, a stent was placed across the aneurysm neck, and one patient underwent additional coiling. Unfortunately, all 3 patients remained symptomatic at their latest follow-up. ConclusionBecause of the intimate anatomic environment of the cavernous sinus, neural elements within it may be particularly susceptible to persistent mass or dynamic effects exacerbated by remnant or recurrent flow across the neck of a coiled aneurysm. These 3 cases prompted the authors to advocate for more aggressive efforts to achieve and maintain CCA occlusion. Furthermore, when such efforts are unsuccessful, consideration of traditional carotid occlusion strategies with or without bypass is warranted.

External carotid artery stenting to treat patients with symptomatic ipsilateral internal carotid artery occlusion: A multicenter case series

BACKGROUNDThe external carotid artery (ECA) anastomoses in many distal territories supplied by the internal carotid artery (ICA) and is an important source of collateral circulation to the brain. Stenosis of the ECA in ipsilateral ICA occlusion can produce ischemic sequelae. OBJECTIVETo examine the effectiveness of ECA stenting in treating symptomatic ipsilateral ICA occlusion. METHODSWe retrospectively reviewed patient databases from 5 academic medical centers to identify all individuals who underwent ECA stenting after 1998. For all discovered cases, coinvestigators used a common submission form to harvest relevant demographic information, clinical data, procedural details, and follow-up results for further analysis. RESULTSTwelve patients (median age, 66 years; range, 45–79 years) were identified for our cohort. Vessel disease involvement included severe ECA stenosis ≥ 70% in 11 patients and ipsilateral ICA occlusion in all patients. Presenting symptoms included signs of transient ischemic attack, stroke, and amaurosis fugax. ECA stenting was associated with preservation of neurological status in 11 patients and resolution of symptoms in 5 patients at a median follow-up time of 26 months (range, 1–87 months; mean, 29 months). Symptomatic in-stent restenosis did not occur within any patient during the follow-up course. CONCLUSIONWe found ECA stenting in symptomatic ipsilateral ICA disease to be a potentially effective strategy to preserve neurological function and to relieve ischemic symptoms. Further investigation with larger studies and longer follow-up periods is warranted to elucidate the true indications of this management strategy.

Techniques and Outcomes of Gore-Tex Clip-Wrapping of Ruptured and Unruptured Cerebral Aneurysms

OBJECTIVE Some aneurysms without a definable neck and associated parent vessel pathology are particularly difficult to treat and may require clipping with circumferential wrapping. We report the largest available contemporary series examining the techniques of Gore-Tex clip-wrapping of ruptured and unruptured intracranial aneurysms and patient outcomes. METHODS The presentation, location, and shape of the aneurysm; wrapping technique; outcome at discharge and last follow-up; and any change in the aneurysm at last angiographic follow-up were reviewed retrospectively in 30 patients with Gore-Tex clip-wrapped aneurysms. RESULTS Gore-Tex clip-wrapping was used in 8 patients with ruptured aneurysms and 22 patients with unruptured aneurysms. Aneurysms included 23 fusiform, 3 blister, and 4 otherwise complex, multilobed, or giant aneurysms. Of the 30 aneurysms, 63% were in the anterior circulation. The overall mean patient age was 52.5 years (range, 17-80 years). Postoperatively, there were no deaths or worsening of neurologic status and no parent vessel stenoses or strokes. The mean Glasgow Outcome Scale score at last follow-up was 4.7. The mean follow-up time was 42.3 months (median, 37.0 months; range, 3-96 months). There were 105.8 patient follow-up years. Aneurysms recurred in 2 patients with Gore-Tex clip-wrapping. No patients developed rehemorrhage. Overall risk of recurrence was 1.9% annually. CONCLUSIONS Gore-Tex has excellent material properties for circumferential wrapping of aneurysms and parent arteries. It is inert and does not cause a tissue reaction or granuloma formation. Gore-Tex clip-wrapping can be used safely for microsurgical management of ruptured and unruptured cerebral aneurysms with acceptable recurrence and rehemorrhage rates.

Dolichoectatic aneurysms of the vertebrobasilar system: clinical and radiographic factors that predict poor outcomes

OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

Diagnostic and Surgical Implications of Ventral Vertebrobasilar Displacement by Posterior Fossa Neurenteric Cysts

OBJECTIVE Neurenteric cysts (NECs) are uncommonly encountered lesions of the central nervous system with heterogeneous imaging characteristics. The object of this study was to review the preoperative imaging findings represented among a cohort of surgically treated posterior fossa NECs. These findings are considered in the context of surgical technique, and inform an understanding of aberrant neuroembryological development associated with NECs. METHODS A single-institution, multisurgeon series of 7 consecutive patients (5 female and 2 male patients, mean age 36 years, range 19 to 57 years) treated surgically for histopathologically confirmed posterior fossa NECs was retrospectively reviewed. Lesion imaging and anatomic characteristics were noted on preoperative magnetic resonance imaging (MRI). Imaging comparisons were made against an additional cohort of 266 consecutive surgically treated posterior fossa masses to validate unique anatomic findings. RESULTS T1 and T2 MRI signal characteristics were variable when compared across lesions. All NECs were found to be anteriorly located within the posterior fossa, but always situated between the brainstem pial surface and the vertebrobasilar system, causing ventral displacement of vertebrobasilar vessels. CONCLUSIONS Posterior fossa NECs display variable patterns of MRI signal and are commonly considered as part of a broad differential of cystic posterior fossa masses. We identified tumor insinuation between the ventral brainstem and vertebrobasilar system as a highly sensitive and specific radiographic sign for NECs. This finding was not observed among a large cohort of posterior fossa masses representative of other multiple pathologies.

A von Hippel-Lindau disease-associated microcystic adenoma of the ethmoid sinus: case report.

BACKGROUND AND IMPORTANCE:We present a unique case of an anterior cranial base von Hippel-Lindau disease (VHL)–associated microcystic neoplasm. To determine the lesions relationship with VHL and its appropriate management, we discuss its salient clinical, pathological, and molecular features. CLINICAL PRESENTATION:A 36-year-old woman with VHL presented with a 3-month history of phantosmia. Serial magnetic resonance imaging studies revealed a lesion within the ethmoid and frontal sinus region that was first evident 18 months before symptom development and demonstrated progressive growth over the interval period. The lesion was resected via a transbasal approach. Histopathological and immunohistochemical analysis revealed a microcystic lesion composed of bland clear cells and underlying endothelial cells consistent with a VHL-associated microcystic neoplasm that are not known to metastasize. Molecular testing demonstrated loss of heterozygosity of the VHL locus, verifying the tumor as a VHL-related neoplasm. CONCLUSION:Because primary VHL-associated microcystic tumors in the anterior cranial base have not been described previously, the natural history of these tumors remains unclear. Based on the benign features of these lesions, they can be managed conservatively with close observation and surgical intervention reserved for those that produce symptoms.

Use of Intracranial Pressure Monitoring Frequently Refutes Diagnosis of Idiopathic Intracranial Hypertension

BACKGROUND The diagnosis and management of patients with idiopathic intracranial hypertension (IIH) frequently relies on lumbar puncture to ascertain intracranial pressure (ICP). However, ICP values derived this way may be spurious owing to patient body habitus and behavior. We recently incorporated direct continuous ICP monitoring into the work-up for IIH. METHODS Through billing records, we identified all patients during a 3-year period who had a diagnosis of IIH and who underwent ICP monitoring before shunt placement or revision. Patient demographics and clinical data were reviewed. RESULTS Of 30 patients who underwent ICP monitoring with an intraparenchymal wire, 17 had undergone lumbar puncture within the previous 6 months. Results from lumbar punctures showed an elevated opening pressure in all 17 patients, whereas only 2 patients (12%) were found to have consistently elevated ICP with direct ICP monitoring. Of 15 patients being evaluated for shunting, 4 (27%) were found to have elevated ICP. Of the 15 patients with existing shunts, 2 patients (13%) were found to have malfunctioning shunts after pressure monitoring, and 3 patients (20%) had shunts that were found to be unnecessary and were removed. No patient experienced any complication from invasive monitoring. CONCLUSIONS Direct ICP monitoring is the gold standard for determining ICP and can be safely and effectively applied to the work-up and treatment of patients with IIH to reduce the occurrence of misdiagnosis and unnecessary surgery.