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Intracranial Arteriovenous Malformations
Introduction
An intracranial arteriovenous malformation (AVM) is an abnormal connection between arterial and venous vessels without intervening capillary structures. The lack of capillary components results in arterialized veins within a high-flow, low-resistance shunt system.[1] Cerebral AVMs convey a 1% annual risk of epilepsy and a 3% annual risk of hemorrhage.[2] The annual risk of hemorrhage is 2.3% for unruptured AVMs and 4.8% for previously ruptured AVMs.[3][4] Intracranial AVMs vary significantly in size, location, and vascular flow dynamics. AVMs are most commonly identified within the cerebral cortex, brainstem (pons and midbrain), and the cerebellum.[2] AVMs can also be found in the spinal cord.[2]
When ruptured, intracranial AVMs usually present with focal neurological deficits, seizures, and sequelae of increased intracranial pressure. Treatment modalities include surgical resection, endovascular embolization, and stereotactic radiosurgery.[5] The Spetzler-Martin grading scale is a widely used classification system for intracranial AVMs to guide decision-making based on surgical morbidity. (Please refer to "Spetzler-Martin Arteriovenous Malformation Grading System" in the Evaluation section for more information on this classification system.) As the Spetzler-Martin grade increases, so does the risk of surgical morbidity and mortality.
Etiology
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Etiology
Although the exact mechanism of intracranial AVM formation is not fully understood, they are believed to result from an abnormal arrest during embryologic vascular development. Approximately 5% of AVMs are identified in patients with inherited disorders such as autosomal dominant hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome.[6][7] Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a recently described systemic disorder with an autosomal-dominant inheritance pattern that is characterized by multiple small AVMs in the limbs and face.[7]
Multiple genetic mutations have been noted in patients with sporadic AVMs that include somatic activating KRAS mutations, a stop-gain mutation in SMAD9, and increased Notch-3 receptor expression.[8][9][10][11] Increased KRAS activity leads to increased MAPK/ERK pathway activity with downstream elevations in Notch signaling and angiogenesis factors.[8] A significantly lower level of SMAD9 in AVM vessels was observed as was a decrease in SMAD4 phosphorylation. SMAD4 is a downstream factor in the MAPK/ERK pathway.[9] In 2015, Hill-Fellberg et al discovered a significant increase in Notch-3 receptor expression in AVM vasculature compared to normal brain samples without AVMs. In addition, they found a significant decrease in Notch-1 and an increase in Notch-4 receptors.[10] More recently in 2020, Hauer et al evaluated genetic alterations in intracranial AVMs using next-generation RNA sequencing of 12 AVMs and 16 healthy control subjects. Over 700 genes were upregulated in the AVM samples, including those involved in transforming growth factor-β (TGF-β) signaling, the extracellular matrix composition, inflammation, and the angiotensin-Tie pathway.[12]
Epidemiology
Up to 88% of intracranial AVMs are asymptomatic. Of those patients who are symptomatic, 45% present with hemorrhage.[13] A Randomized Trial of Unruptured Brain AVMs (ARUBA) trial identified a 2.2% annual risk of hemorrhage for unruptured cerebral AVMs.[14] The incidence of intracranial AVMs is 1.12 to 1.34 per 100,000 persons, which is significantly lower than that for cerebral aneurysms and other cerebral vascular malformations.[15] No significant sex predisposition is noted in adults.[6] A meta-analysis by Gross and Du published in 2013 reported that the average age at presentation was 33.7 years, with 36% to 38% of initial presentations being first-time hemorrhages.[16] Intracranial AMVs account for 33% of intracranial hemorrhages in patients in the third and fourth decades of life. A 0.02% incidence of intracranial AMVs has been reported in the pediatric population without a sex predilection.
Pathophysiology
Intracranial AVMs are abnormal arterial to venous structural connections without capillaries or intervening brain tissue. AVMs demonstrate nonphysiological hemodynamics which affects the structure of the vessels within these typically high-flow, low-resistance shunts. This shunting of blood leads to higher-than-normal flow in both the feeding arteries and draining veins.[3] These hemodynamic forces cause progressive vascular remodeling that includes arterial wall thickening, smooth muscle cell phenotype transformation, and immune/inflammatory infiltration.[17][18][19] In addition, the increased hemodynamic stress within the venous system results in to venous hypertension with chronically elevated flow leading to venous outflow stenosis.[18] The low-resistance shunt through the AVM nidus can divert blood flow away from adjacent brain parenchyma that causes "arterial steal." Because of the chronically increased hemodynamic stress on the vessel walls, some intracranial AVMs are accompanied by arterial aneurysm development which increases the risk for intracranial hemorrhage in patients.[20][3]
Histopathology
Histopathological examination may demonstrate a wide range of vascular wall composition that varies from mature arterial and venous structures to immature, thin, and hyalinized vessel walls. Focal regions of wall hyalinization may extend into vessel lumens. Intimal and smooth muscle layers are often malformed or disrupted in the vasculature.[6] Normal capillary architecture and intervening cortical tissue are not present. Hemosiderin staining from prior microhemorrhages is very commonly visible, even in the absence of clinical symptoms.[6] Histopathological studies have demonstrated silent microhemorrhages from nidal blood vessels with perivascular inflammation, neutrophil infiltration into the vessel walls, and an accumulation of macrophages within the vessel walls and adjacent brain parenchyma.[21][22]
History and Physical
Intracranial hemorrhage can result from a variety of pathologies that include chronic hypertension, amyloid angiopathy, vascular malformations, and trauma. Vascular malformations, eg, aneurysms and intracranial AVMs are more likely in occur patients presenting without trauma that are in the second through sixth decades of life that have a significant smoking history and the simultaneous presence of other vascular malformations. The family history may include hereditary hemorrhagic telangiectasia or multiple vascular malformations.
The clinical findings on the physical examination of the patient with an AVM are highly dependent on the location of the intracranial or spinal AVM and the presence or absence of acute hemorrhage. Intracranial AVMs in adults most commonly present with acute hemorrhage. Acute hemorrhage may lead to focal neurological deficits such as weakness, sensory changes, or cranial nerve palsies. Seizures are the second-most common presenting sign and occur in 27% of patients.[2] Seizure presentation is more commonly seen with AVMs located within the temporal lobes. If the hemorrhage is large enough to cause a significant increase in intracranial pressure, patients will often present with headache, nausea and vomiting, and a decreased level of consciousness.
Evaluation
Imaging studies are essential in the evaluation of patients with intracranial AVMs. Patients presenting with headaches or neurologic deficits should have an initial computed tomography (CT) scan of the head without contrast. A noncontrast head CT can reveal acute intraparenchymal hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage and exclude an ischemic injury and other nonhemorrhagic pathologies, eg, lesions or masses. A noncontrast head CT may demonstrate only a subtle hyperdensity in a patient with an unruptured AVM, making their detection difficult.[23]
CT angiography (CTA) provides excellent spatial resolution of vascular architecture. Valuable information concerning the AVM nidus structure, the presence or absence of deep draining veins and associated aneurysms within the intracranial AVM, and the location of significant feeding arteries can be visualized with CT angiography.[23] [24]A study by Gross et al demonstrated that CT angiography detected 90% of cerebral AVMs compared to magnetic resonance angiography (MRA), which had only a 74% sensitivity.[25] Digital subtraction catheter angiography (DSA) is the gold standard for vascular imaging, usually via femoral artery access, that offers higher spatial and temporal sensitivity than other noninvasive imaging modalities.[26] In addition to improved sensitivity, DSA allows for better demonstration of deep venous drainage and associated aneurysms, which have been reported to increase the risk of spontaneous rupture.[27][28][16] Other risk factors for AVM rupture include increasing patient age and having a cerebellar location.[27] Contrast-enhanced MRA offers high spatial resolution and is a valuable adjunct to DSA for evaluating feeding vessels.[29]
In addition to imaging studies, an initial laboratory evaluation must be performed to determine the coagulation status of the patient, their renal function before contrast administration during imaging, and overall health status before considering potential interventions. These laboratory studies often include, but are not limited to, a complete blood count with differential, a comprehensive metabolic panel, an international normalized ratio (INR), a prothrombin time (PT), a partial thromboplastin time (PTT), and a type and screen for possible blood transfusion.
Treatment / Management
Ruptured Intracranial Arteriovenous Malformation Management
In patients presenting with a ruptured AVM, the initial management follows the AHA/ASA guidelines for the Management of Spontaneous Intracerebral Hemorrhage.[3] Initially, patients should be assessed and stabilized from a cardiorespiratory standpoint, coagulopathies should be reversed, and patients should be treated for fever, hyperglycemia, and intracranial hypertension. External ventricular drainage may be indicated if there is intraventricular hemorrhage extension and hydrocephalus is present. Emergent surgery may be necessary in cases of large hemorrhages that cause mass effect, midline shift of the brain, and coma. These cases are often treated with decompressive hemicraniectomies, with or without clot evaluation, to decrease intracranial pressure and relieve mass effect on the brain.
Several studies have investigated the optimal timing of AVM surgery after rupture. In a cohort of 87 patients, earlier treatment (post-bleed days 1 to 20) was associated with lower health care costs but similar neurological outcomes compared with delayed surgery (post-bleed days 21 to 180).[30] A more recent meta-analysis found improved outcomes in patients with delayed surgical intervention more than 48 hours after the initial rupture.[31] In a report of 55 patients who underwent delayed treatment of a ruptured AVM by more than 4 weeks, the rehemorrhage rate was only 0.6%, highlighting the safety of delayed treatment.[32](A1)
Unruptured Intracranial Arteriovenous Malformation Management
In patients presenting with unruptured AVMs, the decision to treat the patient or monitor the AVM needs to be examined with respect to the risk of AVM rupture. The risk of AVM rupture was evaluated in the A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial. This study revealed a decreased risk of stroke and mortality in patients managed conservatively compared to patients who underwent interventional therapy.[13] The ARUBA trial compared medical management alone to medical management combined with a prophylactic intervention considered surgical, endovascular, radiosurgical, or a combination thereof. Out of 223 patients with a mean follow-up of 33.3 months, the primary endpoint of death from any cause or stroke occurred in 11 of 109 (10.1%) patients in the medical group compared to 35 of 114 (30.7%) in the interventional group. These results led to the discontinuation of the study after 6 years.[15](B2)
The final follow-up of the ARUBA trial, where the mean follow-up was extended to 50 months, confirmed that medical management remained superior to interventional therapy (HR 0.31, 95% CI 0.17–0.56).[33] This study may overestimate the risk of surgery and underestimate the risk of medical management because surgical complications are usually evident in the short term, whereas the risks of medical management are related to long-term risks of rupture or mass effect.[34] More recent observational data have challenged the ARUBA conclusions. (A1)
Several studies have shown the benefit of treatment compared to conservative management. A cohort study of 1770 patients showed an estimated 5-year hemorrhage-free survival rate of 96.23% in the intervention group compared to 89.00% in the conservative management group. Subgroup analyses showed that in patients with high-grade AVMs or diffuse niduses, the benefit of treatment was similar to that of patients receiving conservative management.[35] Similarly, a 30-year single-center experience of 107 conservatively managed unruptured AVMs found that 17% of patients experienced at least 1 hemorrhage during observation, with an annual hemorrhage risk of 2.7% and a long-term AVM-related mortality rate of 8%.[36] These study results support the concept that treatment may be offered to specific patients even in the post-ARUBA era. The AHA/ASA scientific statement acknowledges the ARUBA findings and their limitations and endorses both intervention and conservative management as reasonable options for unruptured AVMs, with treatment decisions guided by an individualized risk-benefit analysis.[3]
A meta-analysis of 2,525 patients found an overall annual intracranial hemorrhage risk of 2.3%, where the risk of hemorrhage differed substantially between unruptured lesions (1.3%, 95% CI 1.0–1.7) and previously ruptured lesions (4.8%, 95% CI 3.9–5.9).[3] The Multicenter Arteriovenous Malformation Research Study (MARS) of unruptured AVMs reported an annual intracranial hemorrhage rate of 1.40 per 100 person-years, which is lower than the commonly cited 2% to 4% estimates.[27] Risk factors for AVM rupture that have been consistently identified include a history of a prior hemorrhage, deep AVM location, exclusively deep venous drainage, and the presence of associated feeding artery aneurysms.[3]
The MARS study identified increasing age, flow-associated arterial aneurysms, and cerebellar or deep supratentorial location as independent risk factors for AVM rupture in the untreated course. The management of women of reproductive age with AVMs also requires special consideration. A systematic review of over 2400 women found that the overall hemorrhage rate in untreated women was 2.6%, but the rate of having an initial hemorrhage during pregnancy and postpartum was greater than during nonpregnant fertile time periods (11% vs. 6.7%). The risk of hemorrhage was particularly elevated during the second and third trimesters in comparison to the time of delivery and puerperium, which carried a lower risk.[37] A large prospective cohort study from China confirmed that the risk of AVM rupture was significantly higher during pregnancy compared to nonpregnancy periods, where the independent risk factors included an adolescent or advanced-age pregnancy, prior AVM rupture, diffuse nidus, and multifetal pregnancy.[38] The AHA/ASA scientific statement on maternal stroke notes that the risk of AVM hemorrhage in pregnancy remains controversial, with some studies suggesting no difference, while other studies suggest a 3-fold increased risk.[39](A1)
The VALE scoring system was developed to help predict the risk of AVM rupture by incorporating variables, eg, venous drainage pattern, AVM location, lesion size, and prior hemorrhage. This system demonstrated superior discriminatory ability compared to the R2eD scoring system and provides meaningful risk stratification for clinical decision-making.[40] These scoring systems help determine which patients should undergo an intervention or conservative management.(A1)
Seizures are the second most common presentation for AVMs following hemorrhage.[41] Risk factors for seizure presentation include temporal and frontal lobe locations, cortical involvement, superficial topography, superficial venous drainage, presence of venous varices, a nidus diameter greater than 3 cm, and an arterial border-zone location.[3] Standard anti-epileptic therapy is the primary approach for managing seizures. Prophylactic anticonvulsant medications in the absence of seizures are not routinely recommended.[42]
For patients managed conservatively, long-term surveillance is essential because the hemorrhage risk does not diminish over time.[3] The optimal methods for surveillance of untreated AVMs are not well established in the literature, although surveillance typically involves periodic MRI scanning with and without contrast. The ACR Appropriateness Criteria note that treated lesions usually require long-term follow-up, specifically those AVMs treated with radiosurgery or embolization.[43] The TOBAS (Treatment of Brain Arteriovenous Malformations Study) registry reported that nearly half of all participants were selected for conservative management, demonstrating the importance of ongoing surveillance.[44]
Spetzler-Martin Arteriovenous Malformation Grading System
The primary treatment modalities for intracranial and spinal AVMs include surgical resection, endovascular embolization, stereotactic radiosurgery, or conservative management. These treatment modalities are often used in combination. The Spetzler-Martin AVM Grading System was developed in 1986 to determine the risk of morbidity and mortality with open surgical resection of intracranial AVMs. The grading system requires a correlation between neuroimaging and cerebral angiographic findings. Graded neuroimaging findings include the size and location of the nidus, and graded angiographic findings include the size of the nidus and the pattern of venous drainage. Points are assigned for each finding, and a grade is calculated.[45] The assigned grade is equal to the sum of points from 3 categories; the minimum is grade I (1 point), and the maximum is grade V (5 points).[45] An additional special designation, grade VI, is also used.[45] The following points are assigned for each finding:
- Size of nidus
- Small: < 3 cm = 1 point
- Medium: 3 to 6 cm = 2 points
- Large: > 6 cm = 3 points
- Venous drainage
- Superficial veins only = 0 points
- Deep veins = 1 point
- Eloquence of adjacent brain
- Noneloquent = 0 points
- Eloquent = 1 point
The areas of the brain considered eloquent are the sensory, motor, language, and visual cortices; internal capsule; hypothalamus and thalamus; brainstem; superior, middle, and inferior cerebellar peduncles; and deep cerebellar nuclei.[45] Venous drainage is considered deep if any drainage is to the deep cerebral veins or cerebellar hemispheric veins, unless they drain into the straight or transverse sinuses.[45] In addition to the Spetzler-Martin scale, the Lawton-Young supplementary grading system also incorporates additional factors in evaluating surgical risk. This supplementary scale also includes patient age, hemorrhagic presentation, and compactness of the nidus.[46][47](B3)
Interventions for Intracranial Arteriovenous Malformations
Surgical resection is generally preferred for superficial lesions, and stereotactic radiosurgery is preferred for AVM locations in the deep brain that include the basal ganglia, thalamus, and brainstem.[48][49][48] The risk of perioperative morbidity and mortality increases with increasing Spetzler-Martin grade. This grading system does not necessarily correlate with risks associated with endovascular embolization or stereotactic radiosurgery. However, Spetzler-Martin grades I and II AVMs are usually managed with open surgical resection, grade III AVMs with endovascular embolization, and grades IV and V AVMs with stereotactic radiosurgery.[50][51][50]Endovascular embolization can also be used to decrease the AVM nidus volume before performing stereotactic radiosurgery.[26][52][26] Grade VI AVMs are considered inoperable.[45] (A1)
While detailed surgical strategies are beyond the scope of this review, the basic tenets of AVM resection are as follows. The skin incision and craniotomy should be large enough to ensure adequate exposure of the entire lesion. A surgical adjunct that helps characterize feeding arteries and draining veins is the use of indocyanine green (ICG) videoangiography. The dissection begins with identifying the main arterial feeders, which can be followed towards the nidus, coagulated, and divided. As the feeders are coagulated, dissection should proceed circumferentially around the nidus, with careful attention directed at trying not to coagulate the nidus. As the dissection extends deeper into the brain, the arterial feeders are identified and coagulated. After the arterial feeders are coagulated and the entire nidus is dissected around, the last step is the coagulation and transection of the main draining vein. Once the vein is sectioned, the nidus can be excised en bloc.[53]
Endovascular therapy is primarily used as an adjunct to surgery or radiation treatment and is rarely used as a standalone technique.[54] The Buffalo Score is another grading system that estimates risk and predicts the complications associated with AVM embolization.[55] In a meta-analysis of over 1400 patients who underwent curative embolization, the obliteration rate was 52% with a retreatment rate of 25%.[54] (A1)
Another study reported a 56% obliteration rate with endovascular therapy alone, compared to a 71% obliteration rate with stereotactic radiosurgery.[56] When specifically evaluating obliteration rates for AVMs with Spetzler-Martin grades 1 to 3, a similar rate of 55.3% has been reported.[57] While obliteration rates are lower with embolization alone than with surgery or radiation treatment, the Society of NeuroInterventional Surgery Standards and Guidelines Committee still recommends targeted embolization of high-risk features in ruptured AVMs to reduce the risk of recurrent hemorrhage and also for symptomatic AVMs for which curative therapy is not possible.[26]
Future therapies
The discovery that the majority of sporadic AVMs harbor somatic activating mutations in the KRAS gene and other components of the RAS/MAPK/ERK signaling pathway has led scientists to evaluate new therapeutic targets. Trametinib, an FDA-approved MEK inhibitor, has shown improved survival and reduced hemorrhagic volume in mouse models.[58] Dual MAPK/VEGF inhibition has shown significantly prolonged survival in mice with KRAS-mutated AVMs.[59] Bevacizumab, a monoclonal antibody targeting VEGF, is also under investigation. In a systematic review, Bevacizumab as a standalone treatment showed no reduction in the nidus volume but was associated with clinical and radiographic improvements in patients with perilesional edema following stereotactic radiosurgery.[60] (A1)
Differential Diagnosis
Intracranial AVMs can be diagnosed after symptomatic presentation with hemorrhage, mass effect, or seizures. Intracranial AVMs are also frequently diagnosed in asymptomatic patients that have cranial imaging for an unrelated indication. The differential diagnosis of a patient presenting with an acute intracranial hemorrhage includes AVM, ruptured aneurysm, dural arteriovenous fistula, cerebral amyloid angiopathy, hemorrhagic tumor, lacunar hemorrhage from hypertensive lipohyalinosis, and a traumatic injury. For patients presenting with seizures, the differential diagnosis includes pathologies that cause cerebral edema and include AVM, tumor, abscess, meningitis, and hydrocephalus, or neurologic etiologies causing seizures that include focal cortical dysplasia, mesial temporal sclerosis, and hereditary seizure disorders.
Radiation Oncology
Stereotactic radiosurgery is another modality that is used to treat AVMs.[61] Several classification systems have been developed to predict outcomes after radiosurgery that include the Pittsburgh and Virginia scales.[55] Radiation treatment causes injury to the vascular endothelium that results in proliferation of smooth muscle cells and extracellular collagen deposition. This process then causes progressive stenosis of the arterial vessels and obliteration of the nidus.[62] Radiation can be delivered using different techniques such as the Gamma Knife, linear accelerators (LINAC), or proton beam therapy. The Gamma Knife is the most extensively studied technique for AVMs, although modern LINAC systems can achieve comparable AVM obliteration rates.[63]
AVMs smaller than 3 cm in diameter with deep draining veins located within the eloquent cortex are ideal AVMs for stereotactic radiosurgery treatment, where the morbidity and mortality for open surgical resection of these lesions is considered substantial. Stereotactic radiosurgery can achieve a 70% to 90% AVM obliteration rate in appropriately selected patients.[3] The standard single-treatment radiation dose administered in these cases is 22 Gy, delivered to the 50% isodose line.[64] Radiosurgical treatment for AVMs measuring greater than 10 cm in diameter is still under investigation, where multiple dose fractions are required to deliver an adequate total radiation dose while minimizing the development of adjacent cerebral edema.[65]
Outcomes following radiosurgery are strongly grade-dependent, with higher obliteration rates for lower-grade AVMs. In a multicenter series, Spetzler-Martin grade 1 or 2 lesions had the best treatment outcomes, with 70% of AVMs showing complete obliteration without complications, compared with 56% of grade 3 AVMs and 35% of grade 4 lesions.[66] A meta-analysis of stereotactic radiosurgery for high-grade (Spetzler-Martin grades IV-VI) AVMs found an overall obliteration rate of only 34.2% with a median follow-up of 50 months and a posttreatment hemorrhage rate of 12.2%.[67] The complications of stereotactic radiosurgery for AVM treatment include seizures and hemorrhage during the latency period. The primary concern for stereotactic radiosurgery in AVM management is that obliteration rate and radiation treatment effects can take 2 to 3 years to occur.[64] During this latent period after treatment, patients remain at risk for AVM rupture.
Prognosis
The prognosis for an intracranial AVM is dependent on the history of rupture. Unruptured AVMs have a 2.2% annual risk of rupture, with previously ruptured AVMs having a 4% annual risk.[64] In 2019, Fengali et al introduced a predictive index to stratify the risk of hemorrhage that was called the R2eD AVM Score. Factors that increased the risk of hemorrhage included small AVM nidus size, non-White ethnicity, deep brain location, having a single arterial feeder, and deep venous drainage.[68] The volume and location of the rupture determine the extent of the residual neurologic deficit and the likelihood of functional recovery. The Treatment of Brain Arteriovenous Malformations Study (TOBAS) included 2 randomized trials of patients undergoing treatment or conservative therapy for brain AVMs.
In the surgical arm, 88% of patients had curative treatment.[69] In the conservatively managed cohort, 434 patients were included in the study, with a primary endpoint of death or dependency (mRS >2) at 10 years. The primary endpoint was reached in 23/434 (5%) of patients, with worse outcomes occurring in patients with a history of prior AVM rupture, infratentorial AVM locations, and in those older than 55 years of age.[44] Within this registry, endovascular embolization was selected as the primary treatment modality in 116 patients and for an additional 92 patients undergoing presurgical embolization. In this cohort, the primary endpoint of death or disability occurred in 15/106 (14%) of patients in the curative group and in 9/77 (12%) undergoing presurgical embolization. In those where cure was attempted, endovascular therapy alone resulted in an obliteration rate of 30% (32/106).[70] Functional outcome after surgical resection is largely dependent on a history of prior AVM rupture, with a worse prognosis in large AVMs, AVMs with a higher Lawton-Young supplementary grade, and the presence of combined venous drainage.[71]
Complications
The optimal management of intracranial AVMs is still widely debated because the risk of surgical treatment complications must be weighed against the risk of lesion rupture or repeat rupture. Surgical complications include stroke, intracranial hemorrhage, seizure, and death. The ARUBA trial evaluated the cumulative outcomes of intervention for unruptured AVMs compared to the outcomes of observation alone, with a significantly increased rate of death from any cause or stroke in the intervention group.[14]
Other complications of intracranial AVMs include the vascular steal phenomenon and mass effect on the brain. Normal perfusion pressure breakthrough is another complication seen after AVM resections. This phenomenon was first reported by Dr. Spetzler and refers to postoperative edema and hemorrhage.[72][73][74] Due to the high-flow nature of AVMs, the surrounding brain is chronically oligemic, which results in maximal vasodilation in the microvasculature. After AVM resection, the immediate increase in blood flow to the chronically oligemic parenchyma causes cerebral edema and hemorrhage within a few hours to days after the surgical resection. This outcome has resulted in the recommended treatment of staged endovascular embolization followed by maintaining hypotension postoperatively.[75]
Adverse effects of stereotactic radiosurgery can be categorized into early radiation-induced changes, delayed adverse radiation effects, and late radiation-induced complications. Early radiation-induced changes occur in approximately 10% of patients and include perinidal T2-weighted signal changes. The majority of these changes are transient and asymptomatic, although permanent neurological deficits can be seen in 2% to 3% of patients.[3][76] Late adverse radiation effects include delayed cyst formation and chronic encapsulated hematoma development. These delayed findings commonly develop many years after stereotactic radiosurgery treatment.[77][78] Radiation-induced neoplasms have been reported, but these complications are very rare compared to the early and late adverse effects of stereotactic radiosurgery.[79]
Consultations
Patients presenting with intracranial or spinal hemorrhage and radiologic evidence of an AVM require neurocritical care team consultation for the management of blood pressure parameters, neurologic observation, and overall critical care management during the posthemorrhagic period. Neurosurgical consultation at the initial diagnosis of hemorrhage is required. Patients with radiological evidence of an intracranial or spinal AVM require neurosurgical consultation for lesion evaluation, risk stratification, and development of appropriate future intervention plans. If patients present with seizures, neurologic consultation is also beneficial in order to obtain an optimal antiepileptic medication regimen.
Deterrence and Patient Education
Arteriovenous malformations are congenital abnormal connections between arteries and veins without intervening normal brain tissue. Patients with AVMs are often asymptomatic until the third or fourth decade of life. Intracranial AVMs can cause seizures from mass effect on the brain or small hemorrhages, weakness or numbness from mass effect, or rupture with significant hemorrhage. The location of the AVM determines which neurologic symptoms will be present. The treatment of intracranial AVMs is dependent on specific characteristics of the lesion, including its size, location, and the presence of deep draining veins.
Asymptomatic AVMs are often diagnosed during cranial or spinal imaging for evaluation of other neurologic complaints such as headaches or back pain. Patients with incidentally diagnosed AVMs should consult with a neurosurgeon to discuss the risks of and possible disease progression associated with observation alone. Neurosurgical observation over time, in combination with neurologic examinations and surveillance imaging, is highly recommended.
The majority of AVMs are sporadic, although a history of certain disorders, eg, hereditary hemorrhagic telangiectasia, may increase the risk of having multiple AVMs. Treatment options for intracranial AVMs include surveillance with imaging, stereotactic radiosurgery, endovascular embolization, and open surgical resection.
Enhancing Healthcare Team Outcomes
Intracranial AVMs are high-flow vascular shunts lacking capillary beds with abnormal hemodynamics that increase the risk of hemorrhage, seizures, and progressive neurologic injury. Intracranial AVMs may present acutely with headache, focal neurological deficits, seizures, or altered level of consciousness, particularly after AVM rupture. The diagnosis relies on neuroimaging with CT identifying acute hemorrhage and advanced vascular imaging such as CT angiography and digital subtraction angiography being used to define the lesion anatomy and to guide management decisions. Treatment strategies are individualized based on the lesion characteristics and patient factors and include surgical resection, endovascular embolization, stereotactic radiosurgery, or conservative monitoring, with careful risk stratification to balance intervention-related morbidity against the risk of hemorrhage.
Interprofessional collaboration is essential to optimize clinical outcomes and ensure patient safety. Emergency clinicians initiate stabilization, imaging, and hemorrhage management, while radiologists characterize lesion features. Neurologists assist with seizure management and antiepileptic medication regimen selection in addition to acute and chronic stroke management. The critical care team coordinates care for multiple medical comorbidities and is essential for medical optimization during the acute and subacute periods after symptom onset. The neurosurgical, endovascular, and radiation oncology services evaluate, determine, and perform appropriate interventions based on the AVM and patient characteristics. Nurses provide continuous monitoring and early detection of clinical changes, and pharmacists guide medication management, including anticoagulation reversal and blood pressure control. Primary care clinicians and advanced practitioners support longitudinal care, facilitate timely referrals, and reinforce adherence to follow-up evaluations. Coordinated communication and shared decision-making with patients and caregivers enable individualized care plans, reduce complications, and improve long-term outcome results.
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