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Free access

Chul Han, Michael J. Lang, Candice L. Nguyen, Ernesto Luna Melendez, Shwetal Mehta, Gregory H. Turner, Michael T. Lawton, and S. Paul Oh


Hereditary hemorrhagic telangiectasia is the only condition associated with multiple inherited brain arteriovenous malformations (AVMs). Therefore, a mouse model was developed with a genetics-based approach that conditionally deleted the causative activin receptor-like kinase 1 (Acvrl1 or Alk1) gene. Radiographic and histopathological findings were correlated, and AVM stability and hemorrhagic behavior over time were examined.


Alk1-floxed mice were crossed with deleter mice to generate offspring in which both copies of the Alk1 gene were deleted by Tagln-Cre to form brain AVMs in the mice. AVMs were characterized using MRI, MRA, and DSA. Brain AVMs were characterized histopathologically with latex dye perfusion, immunofluorescence, and Prussian blue staining.


Brains of 55 Tagln-Cre+;Alk1 f/f mutant mice were categorized into three groups: no detectable vascular lesions (group 1; 23 of 55, 42%), arteriovenous fistulas (AVFs) with no nidus (group 2; 10 of 55, 18%), and nidal AVMs (group 3; 22 of 55, 40%). Microhemorrhage was observed on MRI or MRA in 11 AVMs (50%). AVMs had the angiographic hallmarks of early nidus opacification, a tangle of arteries and dilated draining veins, and rapid shunting of blood flow. Latex dye perfusion confirmed arteriovenous shunting in all AVMs and AVFs. Microhemorrhages were detected adjacent to AVFs and AVMs, visualized by iron deposition, Prussian blue staining, and macrophage infiltration using CD68 immunostaining. Brain AVMs were stable on serial MRI and MRA in group 3 mice (mean age at initial imaging 2.9 months; mean age at last imaging 9.5 months).


Approximately 40% of transgenic mice satisfied the requirements of a stable experimental AVM model by replicating nidal anatomy, arteriovenous hemodynamics, and microhemorrhagic behavior. Transgenic mice with AVFs had a recognizable phenotype of hereditary hemorrhagic telangiectasia but were less suitable for experimental modeling. AVM pathogenesis can be understood as the combination of conditional Alk1 gene deletion during embryogenesis and angiogenesis that is hyperactive in developing and newborn mice, which translates to a congenital origin in most patients but an acquired condition in patients with a confluence of genetic and angiogenic events later in life. This study offers a novel experimental brain AVM model for future studies of AVM pathophysiology, growth, rupture, and therapeutic regression.

Free access

Jacob F. Baranoski, Ankush Bajaj, Colin J. Przybylowski, Joshua S. Catapano, Fabio A. Frisoli, Michael J. Lang, and Michael T. Lawton

Supracerebellar transtentorial (SCTT) approaches have become a popular option for treatment of a variety of pathologies in the medial and basal temporal and occipital lobes and thalamus. Transtentorial approaches provide numerous advantages over transcortical approaches, including obviating the need to traverse eloquent cortex, not requiring parenchymal retraction, and circumventing critical vascular structures. All of these approaches require a tentorial opening, and numerous techniques for retraction of the incised tentorium have been described, including sutures, fixed retractors, and electrocautery. However, all of these techniques have considerable drawbacks and limitations. The authors describe a novel application of clip retraction of the tentorium to the supracerebellar approaches in which an aneurysm clip is used to suspend the tentorial flap, and an illustrative case is provided. Clip retraction of the tentorium is an efficient, straightforward adaptation of an established technique, typically used for subtemporal approaches, that improves visualization and surgical ergonomics with little risk to nearby venous structures. The authors find this technique particularly useful for the contralateral SCTT approaches.

Open access

Sirin Gandhi, Tsinsue Chen, Justin R. Mascitelli, Claudio Cavallo, Mohamed A. Labib, Michael J. Lang, and Michael T. Lawton

This video illustrates a contralateral supracerebellar transtentorial (cSCTT) approach for resection of a ruptured thalamic cavernous malformation in a 56-year-old woman with progressive right-sided homonymous hemianopsia. The patient was placed in the sitting position, and a torcular craniotomy was performed for the cSCTT approach. The lesion was resected completely. Postoperatively, the patient had intact motor strength and baseline visual field deficits with moderate right-sided paresthesias. The cSCTT approach maximizes the lateral surgical reach without the cortical transgression seen with alternative transcortical routes. Contralaterality is a defining feature, with entry of the neurosurgeon’s instruments from the craniotomy edge of the craniotomy, contralateral to the lesion, allowing access to the lateral aspect of the lesion. The sitting position facilitates gravity-assisted cerebellar retraction and enhances the superior reach of this approach (Used with permission from Barrow Neurological Institute, Phoenix, Arizona).

The video can be found here:

Free access

Michael T. Lawton and Michael J. Lang

Despite the erosion of microsurgical case volume because of advances in endovascular and radiosurgical therapies, indications remain for open resection of pathology and highly technical vascular repairs. Treatment risk, efficacy, and durability make open microsurgery a preferred option for cerebral cavernous malformations, arteriovenous malformations (AVMs), and many aneurysms. In this paper, a 21-year experience with 7348 cases was reviewed to identify trends in microsurgical management. Brainstem cavernous malformations (227 cases), once considered inoperable and managed conservatively, are now resected in increasing numbers through elegant skull base approaches and newly defined safe entry zones, demonstrating that microsurgical techniques can be applied in ways that generate entirely new areas of practice. Despite excellent results with microsurgery for low-grade AVMs, brain AVM management (836 cases) is being challenged by endovascular embolization and radiosurgery, as well as by randomized trials that show superior results with medical management. Reviews of ARUBA-eligible AVM patients treated at high-volume centers have demonstrated that open microsurgery with AVM resection is still better than many new techniques and less invasive approaches that are occlusive or obliterative. Although the volume of open aneurysm surgery is declining (4479 cases), complex aneurysms still require open microsurgery, often with bypass techniques. Intracranial arterial reconstructions with reimplantations, reanastomoses, in situ bypasses, and intracranial interpositional bypasses (third-generation bypasses) augment conventional extracranial-intracranial techniques (first- and second-generation bypasses) and generate innovative bypasses in deep locations, such as for anterior inferior cerebellar artery aneurysms. When conventional combinations of anastomoses and suturing techniques are reshuffled, a fourth generation of bypasses results, with eight new types of bypasses. Type 4A bypasses use in situ suturing techniques within the conventional anastomosis, whereas type 4B bypasses maintain the basic construct of reimplantations or reanastomoses but use an unconventional anastomosis. Bypass surgery (605 cases) demonstrates that open microsurgery will continue to evolve. The best neurosurgeons will be needed to tackle the complex lesions that cannot be managed with other modalities. Becoming an open vascular neurosurgeon will be intensely competitive. The microvascular practice of the future will require subspecialization, collaborative team effort, an academic medical center, regional prominence, and a large catchment population, as well as a health system that funnels patients from hospital networks outside the region. Dexterity and meticulous application of microsurgical technique will remain the fundamental skills of the open vascular neurosurgeon.