Introduction: Surgical management of intertrochanteric hip fractures is a common surgery with low rates of intraoperative complications. Vascular injuries are exceptionally rare when placing an intramedullary nail without open reduction. There are very few reported cases of direct arterial injury and active bleed at the level of the distal interlocking screw following closed reduction and intramedullary nailing of a hip fracture. We report one such case. Case Presentation: An 88-year-old female presented to the emergency department with a left intertrochanteric hip fracture. Closed reduction with a cephalomedullary nail fixation of the left hip fracture occurred as planned without any obvious intraoperative technical issues. The patient remained stable intraoperatively. No open reduction was required. Postoperatively, the patient developed hemorrhagic shock and required massive transfusion protocol. Angiography demonstrated an intramuscular hematoma at the level of the distal intramedullary nail interlocking screw with active extravasation. The patient subsequently required embolization. Nine days following surgery, she began Eliquis for DVT prophylaxis and was ambulating independently with signs of hematoma resolution. Discussion: Profunda femoris artery injury can stem from various mechanisms during surgery. Atherosclerosis places patients at a higher risk of complication due to rigid vessels. In this case, it is believed that drilling beyond the medial femoral cortex led to the arterial injury. Conclusion: Care should be taken to prevent drills from plunging beyond the medial femoral cortex during surgery. Cautious observation of patient's vitals and clinical course can allow for early detection of vascular complication.

Many conditions that neurosurgeons manage are associated with neuro-ophthalmic and neurologic symptoms. Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure with associated signs and symptoms to include visual disturbances, pulsatile tinnitus, and headache. IIH is considered a lifelong disease. Although elevated intracranial pressure itself may not be life-threatening, the real threat for patients with IIH is visual loss. For that reason, it is imperative that a neuro-ophthalmologist and/or comprehensive eye care provider determine visual function (visual acuity and visual fields) in a patient with IIH. Accurate understanding of the diagnostic criteria, interpretation of visual results, and headache history can help the neurosurgeon in determining whether their patient needs surgery. Many patients with IIH also have associated headache and migraine conditions. The collaboration between a neurologist, ophthalmologist, and neurosurgeon is crucial for providing the highest quality of care for patients with IIH.

Bathini, Abhijith MD; Qazi, Zeeshan MBBS, MS, MCh; Bendok, Bernard R. MD, MSCI Author Information

Learning Objectives:After participating in this CME activity, the neurosurgeon should be better able to: Interpret the current evidence regarding the natural history of brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia. Describe the diagnosis and management of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia. Define some of the knowledge gaps in our current understanding of arteriovenous malformations associated with hereditary hemorrhagic telangiectasia. Category: Cerebrovascular Brain arteriovenous malformations (bAVMs) are an important cause of hemorrhagic stroke, with an estimated prevalence of 10 to 18 cases per 10,000 adults.1 Although significant treatment advances have been made, there is a paucity of literature regarding the clinical course of bAVMs in hereditary hemorrhagic telangiectasia (HHT), a condition that confers increased risk of systemic vascular abnormalities.2 Moreover, evidence suggesting a different natural history of HHT-related bAVMs compared with sporadic bAVMs has raised the debate as to whether these lesions should be managed with different guidelines than sporadic bAVMs.3-7 In this article we review the natural history, diagnosis, and management of bAVMs in HHT patients with up-to-date and evidence-based recommendations. Brain Arteriovenous Malformations: Overview bAVMs represent abnormal vascular lesions characterized by the shunting of arterial blood into the venous circulation without a capillary system (Figure 1).8 Patients harboring bAVMs are prone to experience intracranial hemorrhage (ICH), seizures, and neurologic deficits. ICH constitutes the most frequent and serious presentation. The hemorrhage risk of sporadic bAVMs is highly variable, with reported risk concentrated between 1% and 4% per year. Actual risk can vary from 1% to 40% annually depending on presentation, angiographic features, and biological factors, the understanding of which remains elusive to date.8,9Figure 1.: Blood flow in a healthy capillary bed (left) versus in the presence of an AVM (right).Although the etiology of bAVMs remains incompletely elucidated, important evidence on the dynamic nature of bAVMs has expanded on initial conceptions of their congenital origin.10-12 Some authors have theorized that genetic abnormalities alone may not be enough to trigger bAVM formation, and that factors causing angiogenesis may be required. These variables are termed “second hit” and could potentially include different stimuli such as radiation exposure, hypoxic insult, trauma, epilepsy, an inflammatory process, a neuronal migration disorder, hydrocephalus, or a hormonal disturbance.10,12 In a small percentage of cases, bAVMs have been associated with familial occurrence in the presence of genetic syndromes such as HHT and hereditary neurocutaneous angiomatosis.13,14 Although the scope of our article has been centered around bAVMs in the context of HHT, a separate and distinct category of bAVMs termed “familial” is recognized. Familial bAVMs are defined as bAVMs occurring in 2 or more relatives (up to third-degree relatives) in a family without any known associated disorders.11 Hereditary Hemorrhagic Telangiectasia Epidemiology HHT, also known as “Osler-Weber-Rendu disease,” is an autosomal dominant disorder characterized by multisystemic vascular dysplasia.15 The prevalence of HHT is estimated to range from 1 in 5000 to 1 per 10000 people; however, it is postulated to be an underdiagnosed condition due to a variable, age-related clinical expression, and challenges associated with diagnosing exceedingly small arteriovenous malformations (AVMs).14-18 Clinical Diagnosis HHT can present with a wide array of symptoms leading to acute hemorrhage, chronic intermittent bleeding, and multiple complications from aberrant vascular lesions. Epistaxis constitutes the most frequent symptom, followed by mucocutaneous telangiectasias, gastrointestinal tract bleeding, and pulmonary AVM-related symptoms.5,15 In fact, chronic gastrointestinal bleeding, anemia, and symptomatic liver AVMs have been associated with increased mortality.19 Neurologic manifestations can be secondary to emboli related to pulmonary AVMs (PAVMs), cerebral or spinal AVMs, and portal-systemic encephalopathy.20 In about two-thirds of the cases, neurologic symptoms are attributed to PAVMs, which cause paradoxical cerebral emboli resulting in cerebral infarction or brain abscess. Other mechanisms include systemic hypoxia due to right-to-left arteriovenous shunting, air embolism, and secondary polycythemia.3,20,21 As a result, patients may experience headaches, recurrent syncope, diplopia, vertigo, visual and auditory disturbances, dysarthria, focal or generalized seizures, and paresthesias.20 When formulating the diagnosis of HHT, clinicians can refer to the Curaçao criteria, which describes the presence of (i) spontaneous and recurrent epistaxis, (ii) multiple telangiectasias at characteristic sites such as the lips, oral cavity, fingers, or nose, (iii) visceral lesions including gastrointestinal telangiectasia, or pulmonary, hepatic, cerebral and spinal AVMs, and (iv) a family history of a first-degree relative with HHT according to these criteria. A patient can be considered to have a definite, possible, or unlikely diagnosis based on the criteria they meet (Table 1).22 Table 1. - Curaçao Criteria for Clinical Diagnosis of Hemorrhagic Hereditary Telangiectasia The HHT diagnosis is:DefinitePossible or suspectedUnlikely If 3 criteria are presentIf 2 criteria are presentIf fewer than 2 criteria are present CriteriaEpistaxisTelangiectases Spontaneous, recurrent nose bleedsMultiple at characteristic sites:LipsOral cavityFingersNose Visceral lesions Such asGastrointestinal telangiectasia (with or without bleeding)Pulmonary AVMHepatic AVMCerebral AVMsSpinal AVM Family history A first-degree relative with HHT, according to these criteria AVM, arteriovenous malformation. HHT, hereditary hemorrhagic telangiectasia. Adapted from Am J Med Genet. 2000;91(1):66-67. Genetics Approximately 97% of patients with a definite clinical diagnosis have a causative mutation related to alterations in the superfamily signaling genes of transforming growth factor β1 (TGF-β1).23,24 In most cases (∼90%), a loss-of-function mutation in one copy of the endoglin (ENG) or activin-like receptor kinase 1 (ACVRL1) genes has been accounted responsible for the phenotypes HHT type 1 (HHT-1) and HHT type 2 (HHT-2), respectively. Less common phenotypes include HHT-juvenile polyposis syndrome, HHT-like, and RASA-1-related disorder (capillary malformation-arteriovenous malformation syndrome) (Table 2).23 Table 2. - Genetics of Hereditary Hemorrhagic Telangiectasia Phenotype Gene Location Frequency HHT-1 ENG 9q34.11 39%–59% HHT-2 ACVRL1 12q13.13 25%–57% HHT-juvenile polyposis SMAD4 18q21.1 1%–2% HHT-like GDF2 10q11.22 <1% RASA-1 related disorders RASA-1 5q14.3 Unknown HHT, hereditary hemorrhagic telangiectasia. Adapted from J Clin Med. 2022;11:5245. HHT-Related bAVMs: Epidemiology and Clinical Characteristics Accounting for 3% of bAVMs, HHT represents the most common genetic etiology.25-29 Intracranial AVMs are the most common neurovascular manifestation in about 5% to 23% of patients, especially in the phenotypes HHT-1 and HHT-2.3,25,30-34 Findings from a meta-analysis suggest a frequent symptomatic course and higher prevalence in the HHT-1 phenotype.35 Described neurologic manifestations include headaches, bruits, focal or generalized seizures, syncope, transient and permanent focal motor deficits, temporary loss of vision, homonymous hemianopia, or ataxia.20 Of particular significance, bAVMs in HHT patients are diverse. Three main subtypes have been described, including nidal AVMs, capillary vascular malformations (CVMs), and pial arteriovenous fistulas (pAVFs). Nidal AVMs represent the classic architecture of sporadic AVMs, which are vascular lesions comprised of dilated feeding arteries and draining veins with an intervening nidus, an abnormal network of blood vessels. On the other hand, CVMs are an abnormal bunch of smaller vessels without a shunt. As such, they are only seen in the capillary phase of angiograms without a dilated feeding artery or dilated draining vein. pAVFs are often single-hole direct fistulas without an intervening nidus or capillaries. They are considered high-shunt lesions with a dilated and tortuous feeding artery and draining vein. A systematic review studying the prevalence of various brain AVMs noted that nidal AVMs represent the most common subtype (62.3%), followed by CVMs (23.9%) and pial AVFs (10.7%).35 In addition, HHT patients can harbor other nonshunting vascular lesions such as capillary telangiectasias (2.4%), cavernous malformations (3.5%), and developmental venous anomalies (12%).30 Imaging of HHT-Related bAVMs MR imaging modalities are helpful to screen, characterize, and detect high-risk features that could increase the rupture risk of HHT-related bAVMs such as presence of prior hemorrhage, nidus or feeding artery aneurysms, and venous outflow stenoses.36,37 Digital subtraction angiography (DSA) and superselective angiography have been considered ideal methods for diagnosis, as they allow characterization of associated lesions such as aneurysms and venous stenoses, which have been shown to increase the risk of hemorrhage from AVMs.36,38 In fact, many micro-AVMs can be easily missed by other imaging modalities such as MRI and MR angiography (MRA) and can only be detected on DSA.30 However, some vascular malformations are only detected on MR imaging. Therefore, both DSA and MRI are recommended.39 Superselective angiography and 3-dimensional (3D) angiography can be very helpful in localizing and assessing the morphology of these lesions. Data from these images can be integrated into neuronavigation, virtual reality, and augmented reality systems for surgery. Distinct angiographic characteristics of bAVMs can be recognized in patients with HHT (Table 3). These lesions tend to be small, multiple, demonstrate superficial venous drainage, supratentorial localization, and a Spetzler-Martin (SM) grading scale of 2 or less.30,35 Due to the small size of these lesions, it has been suggested that expert neurovascular surgeons and neuroradiologists carefully analyze imaging findings. Additionally, the multiplicity of bAVMs could have clinical relevance in conducting a thorough examination for HHT.25 Table 3. - Characteristics of Brain Arteriovenous Malformations in Patients With Hereditary Hemorrhagic Telangiectasia Feature Description SizeMultiplicityVenous drainageAnatomic locationSpetzler-Martin gradeAssociated findings <3 cm≥2 lesionsSuperficialSupratentorial≤2Low incidence of high-risk features including venous stenosis, flow-related aneurysms Postcontrast high spatial-resolution volumetric MRI with susceptibility-weighted imaging (SWI) and time-of-flight MRA has been recommended for screening purposes.36 Comparison of various pulse sequences has revealed that more bAVMs were seen with 3D and 2D postgadolinium T1-weighted sequences than with SWI, MRA, or T2 imaging, particularly at 3.0T rather than 1.5T.39 For patients who had catheter angiogram-confirmed bAVMs, the sensitivity and specificity of MR imaging for detecting the bAVMs were 80.0% and 94.4%, with a negative predictive value of 65.4% in one study.39 However, in pregnant patients, MRI without contrast is advisable.14 Guidelines recommend that in pregnant women with incidental bAVMs seen on MRI, potential treatment should be deferred until after delivery.2 With the use of contrast-enhanced MRI and multiphase biplanar selective 4-vessel angiography, Krings et al40 characterized the 3 distinct phenotypes of HHT-related bAVMs that have been used broadly in the literature (Table 4). Table 4. - Imaging Characteristics of bAVM Subtypes bAVM Subtype Imaging Findings Nidus-type bAVM Presence of a shunt with early filling of a vein through a dilated network of abnormal vessels Capillary vascular malformation Blush of abnormal vessels without visible shunt in the capillary phase of angiography and absence of dilated feeding arteries or draining veins in MRI Pial AVF Absence of an intervening nidus between the feeding artery and the draining vein in the presence of a shunt AVF, arteriovenous fistula; bAVM, brain arteriovenous malformation. Natural History–HHT-Related bAVMs Over the past several decades, few studies have explored the bleeding risk of vascular malformations associated with HHT,3-6 with one of the shortcomings being the nondifferentiation of the natural history of the distinct bAVMs seen with HHT. A 2000 study involving 196 HHT patients, of which 24 subjects presented with 28 bAVMs, estimated the annual hemorrhage rate to be 0.4% to 0.7%. This value was retrospectively calculated assuming a congenital nature of bAVMs and during an observation period extending from the time of birth to the time of hemorrhage or treatment.3 This methodology tends to underestimate the risk of bleeding given that risk is not equally distributed throughout life span. In 2015, a large-scale study from the Brain Vascular Malformation Consortium (BVMC) estimated an overall ICH rate of 1.02% per year (95% confidence interval, 0.42%–2.44%) with higher risk of subsequent hemorrhage in ruptured versus unruptured lesions at presentation (10.07 % vs 0.43%).4 This study included 153 patients with HHT-related bAVMs who were followed up for a mean period of 3.2 ± 4.3 years. The ICH rate was calculated as “number of first ICH events/patient-years at risk × 100.” The follow-up time was determined after the date of bAVM diagnosis until the date of hemorrhage, censoring at the date of the first treatment, death, or last follow-up, and truncated at 15 years from diagnosis.4 In 2016, Yang et al5 compared for the first time the bleeding risk of HHT-related bAVMs between 12 and 519 patients with and without HHT, respectively. The calculation was based on the number of ICHs divided by the total patient-years or lesion-years during the observation period of bAVMs, which was defined as the interval between the date of diagnosis and the date of the last follow-up.5 Although HHT-related bAVMs had a lower annualized bleeding risk than the sporadic type (1.3% vs 3.0%; P = 0.37), this difference was not statistically significant and the small number of patients along with the retrospective evaluation of hemorrhage represented major limitations.5 It is again worth mentioning that the vascular lesions in HHT are diverse, ranging from an elevated risk for direct pial fistulas to low-risk capillary malformations. From a hemodynamic standpoint, direct pial fistulas represent high-pressure shunting systems with increased risk of hemorrhage as compared with capillary malformations, which are nonshunting, low-pressure systems. Pial fistulas are therefore more likely to be symptomatic and present at an earlier phase of life as supported by the Bicetre series, in which the average age of presentation in patients with AVFs was 3 years.41 The majority of patients in that series were AVFs followed by nidal AVMs, with more than 50% of the patients symptomatic. On the other hand, CVMs are likely highly benign lesions. In 2017, Brinjikji et al6 studied 22 HHT patients with 42 CVMs, who were followed up for 4.6 ± 3.7 years. There was no incidence of hemorrhage, development of seizure, or other neurologic deficits related to those lesions. A potential caveat of large population-based studies describing the natural history of HHT-related bAVMs is the lack of differentiation of vascular lesions in these patients. Therefore, the reported hemorrhage risk is an averaged bleeding risk from all types of lesions and is not likely representative of true brain AVMs (nidal AVMs) when comparing with sporadic AVMs. Considering the substantial proportion of CVMs in HHT patients with benign course, there is a bias toward false lower rate of hemorrhage in these patients. In summary, the comparison of bleeding risks between sporadic and HHT-related bAVMs remains a matter of debate as the current evidence remains inconclusive. Limitations in calculating a true estimate of the hemorrhage risk have included differences in screening protocols, the small sample size of enrolled subjects, nonstratification of bAVM subtypes, short follow-up times, and retrospective assessment of the hemorrhagic risk. This significant knowledge gap has generated interest in further studies that will hopefully shed light on this important question. One such effort is being driven by the BVMC, which has established national and international collaborations to retrieve patient data and conduct large-scale studies through HHT Centers of Excellence.42 Treatment of HHT-Related bAVMs Management of these lesions remains controversial, and establishing a treatment protocol is difficult because of the diverse subtypes of bAVMs.3-5,7,14,35 Management options have included conservative treatment, microsurgery, radiosurgery, and embolization therapy. Conservative Treatment The main rationale for recommending conservative management is the avoidance of procedural risks.3-5,43 Specifically, this approach has been advised for CVMs.6 It is important to recognize that patients with HHT-related bAVMs are young compared with sporadic AVMs.5 Considering the small size and lower SM grade in these lesions, one may argue favoring treatment to achieve cure with minimal risk. Microsurgical Intervention Because of its curative potential and the possibility of protecting patients from future hemorrhage, microsurgery is one of the main treatment options for bAVMs.43 Patients with prior evidence of hemorrhage can particularly benefit from surgical intervention as they are at higher risk of recurrent ICH.4,43,44 Another argument for considering surgical resection is the fact that these lesions have favorable angiographic characteristics including smaller size, superficial and supratentorial location, predominantly superficial feeders with an SM grading scale of 2 or less.7,45 Meybodi et al43 suggested that surgical resection is a reasonable option associated with minimal surgical morbidity. The authors found no significant difference in the functional outcomes—measured by the modified Rankin scale—between 19 patients who underwent surgery and 22 patients who received nonsurgical treatment (ie, observation, radiosurgery, or embolization). However, the conclusions of this study are limited by the small sample size and short follow-up time. It is important to acknowledge that the presence of multiple lesions requires thorough preoperative planning and possibly even staged procedures.7 Preoperatively, it is advisable that patients should be screened for PAVMs. In case PAVMs are found, preventative embolization is recommended to reduce perioperative risks such as intrapulmonary hemorrhage, stroke, or brain abscess. When emergent surgery of bAVMs is needed, and the PAVM status is unknown, PAVMs should be assumed to be present, and precautions should follow, including antibiotic prophylaxis and the use of intravenous air filters until screening can be done postoperatively.7 Stereotactic Radiosurgery Stereotactic radiosurgery (SRS) represents a noninvasive technique that allows gradual sclerosis of the blood vessels and thrombosis of the bAVM.46 In theory, SRS could be beneficial as small lesions with Virginia Radiosurgery AVM grade 1 or 2 can respond favorably. However, it is worth mentioning that patients could remain at risk for bleeding during the latency period between the radiation administration period and bAVM obliteration. In addition, complications from radiation can include necrosis, edema, and cyst formation.7,43,46-48 Embolization Therapy Embolization can in select cases be used as a complementary therapy to microsurgery or radiosurgery.46 Although the small size of the lesions could be advantageous for effective treatment, the associated distal and small feeding arteries and superficial location can represent a challenge for safe and successful catheterization of the arteries for embolization.7 Case Illustration To illustrate the complex decision-making scenario, we present the case of a 65-year-old man who was diagnosed with HHT after an episode of hemoptysis secondary to PAVMs. Subsequently, he was referred to the neurosurgical department for a brain MRI screening. He was otherwise neurologically asymptomatic, and his neurologic examination was intact. A brain MRI revealed a small area of chronic infarction with encephalomalacia and gliosis in the right cerebellar hemisphere (Figure 2). An adjacent subcentimeter area of subtle enhancement in the posterior right cerebellar hemisphere without an obvious dilated artery or draining vein suggested the presence of a small “CVM” (Figure 3A). A second focus of vascular enhancement was seen in the left posterior inferior cerebellar vermis (Figure 3B). In addition, a third area of subtle enhancement consisted of a faint vascular blush in the right parietal lobe posteriorly within a sulcus (Figure 3C).Figure 2.: Brain MRI findings.Figure 3.: Right vertebral lateral angiogram (A) showing the right cerebellar AVM feeding from the right AICA/PICA. Superselective catheterization of the right AICA/PICA and lateral angiogram (B) showing the AVM with the draining vein. Left vertebral anteroposterior (AP) (C) and lateral (D) angiogram showing the vermian AVM fed by the left PICA. Right MCA superselective catheterization and AP (E) and lateral (F) angiogram showing the right parietal AVM feeding from the distal branches of superior division of MCA.A cerebral angiogram revealed a subcentimeter right cerebellar AVM with a compact nidus fed by the distal right AICA/PICA (anterior inferior cerebellar artery/posterior inferior cerebellar artery) with early venous drainage (Figures 3A and 3B), and a vermian AVM being supplied by the left PICA (Figures 3C and 3D). Additionally, a subcentimeter right parietal AVM was seen being fed by the distal superior division MCA (middle cerebral artery) with a large cortical draining vein into the superior sagittal sinus (Figures 3E and 3F). Furthermore, a functional MRI was performed to visualize the motor tracts and speech area in relation to the right parietal AVM [Video 1]. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1.","caption":"Case illustration, microsurgical resection of HHT-related brain AVMs guided by augmented reality.","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_27fj3hch"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} After careful discussion with the patient and his family regarding the available management options, risks, and benefits, he opted to undergo microsurgical resection of his 3 bAVMs [Video 1]. The surgery was performed in a staged fashion: in the first surgery, the 2 cerebellar bAVMs were resected from a midline suboccipital approach. Subsequently, after several months of recovery, the right parietal AVM was resected. For the bAVM located in the right parietal lobe, motor mapping and augmented reality were used to enhance visualization and safe resection of the bAVM. His neurologic course was uneventful on follow-up, with no associated neurologic deficits. Postoperative angiograms demonstrated no residual AVM in the surgical bed along the right cerebellar, left median vermian region, and right parietal lobe [Video 1]. International Guidelines for the Diagnosis and Management of HHT Although controversy persists regarding the management options in these patients, important efforts to optimize HHT patient care have led to the publication of the International Guidelines for the Diagnosis and Management of HHT. The International Guidelines for the Diagnosis and Management of HHT, published in 2011 and updated in 2020, have guided clinicians to standardize their practice with evidence-based recommendations.2,14 These statements have focused on 3 main groups, including adult, pediatric, and pregnant patients affected by HHT. The management of adult patients with brain vascular malformations has discussed the MRI screening protocols, invasive testing, definitive management, and decision-making during pregnancy (Table 5). Moreover, it has been recommended that patients with HHT and bAVMs should be referred to centers with neurovascular expertise for invasive testing, individualized management, and definitive treatment, especially in cases presenting with hemorrhage secondary to bAVMs.14 Table 5. - Recommendations for the Management of Brain Vascular Malformations in Adult Patients With Hereditary Hemorrhagic Telangiectasia Expert Panel Recommendation Agreement Level of Evidence Strength of Recommendation The use of MRI for brain vascular malformation screening in adults with possible or definite HHT using a protocol with and without contrast administration and using sequences that detect blood products to maximize sensitivity 100% III Weak Adults presenting with an acute hemorrhage secondary to a brain vascular malformation be considered for definitive treatment in a center with neurovascular expertise 94% III Strong All other adults with brain vascular malformations should be referred to a center with neurovascular expertise for invasive testing and individualized management 84% III Strong Pregnant women with suspected or confirmed HHT harboring an asymptomatic brain vascular malformation during pregnancy can have definitive treatment of their brain vascular malformations deferred until after delivery of their fetusThe expert panel recommends that the delivery of the fetus follows obstetrical principles 80% III Weak HHT, hereditary hemorrhagic telangiectasia. In the pediatric population, the panel of experts has based most of their recommendations on case series studies and has included: (1) performing screening for brain vascular malformations in asymptomatic children with HHT or at risk for HHT at the time of presentation/diagnosis, and (2) treatment of these lesions with high-risk features (eg, prior microhemorrhage, venous stenosis, and feeding artery aneurysms).14 For pregnant women, the expert panel has recommended (1) testing with unenhanced MRI in pregnant women with symptoms suggestive of brain vascular malformations, (2) management at a tertiary care center by a multidisciplinary team if they have untreated pulmonary AVMs and brain vascular malformations or have not been recently screened for pulmonary AVMs, and (3) that patients with known, non–high-risk brain vascular malformations can labor and proceed with vaginal delivery, and may require an assisted second stage of labor on a case-by-case basis.14 Conclusions HHT is a clinical condition that confers increased risk for systemic vascular abnormalities, including bAVMs. Although HHT has been deemed to be a rare condition, it constitutes the most common genetic cause of bAVMs. Evidence about the comparative bleeding risk of HHT-associated bAVMs compared with sporadic AVMs remains inconclusive and further investigation is needed. Microsurgery can be offered to the majority of patients with a high safety profile, but it is important to distinguish AVMs and fistulas from capillary malformations. True capillary malformations do not need treatment. The International Guidelines for the Diagnosis and Management of HHT advise referring patients to centers with neurovascular expertise for testing, definitive treatment, and multidisciplinary management. However, as a treatment protocol has not been established, it is relevant to offer management on a case-by-case basis considering the clinical history of HHT, bAVM subtype, high-risk features for hemorrhage, and patients' preferences.

Bathini, Abhijith MD*; Olson, Vita BS*; Batjer, H. Hunt MD*; Bendok, Bernard R. MD, MSCI*,‡,§,‖,¶ Author Information

Improved Patient Outcomes In A Specialized Neurological Emergency Department Introduction: Stroke is now the fifth leading cause of death in the U.S., but remains the leading cause of long term disability. Target: Stroke helps hospitals achieve improved stroke outcomes through reduced door-to-needle times for eligible stroke patients. Phase III of the American Heart Association/American Stroke Association initiative set more aggressive targets for timely treatment with IV alteplase. To achieve rapid treatment times and better patient outcomes, we created a neurologic emergency department (Neuro ED). Neuro ED hours are staffed by emergency physicians with specialized neuroscience training and administer IV alteplase independently, compared to the traditional ED (TED) where emergency providers consult neurology. Methods: This is a retrospective observational study from 2019-2021 comparing outcomes of acute ischemic stroke patients who received IV alteplase following implementation of the Neuro ED compared to a TED. The following metrics were calculated for each patient: Door to Needle times (DTN), door to CT times (DTCT), and pre and post National Institute of Health Stroke Scale (NIHSS) Results: 74 patients were treated in the Neuro ED and 45 patients were treated in the TED. Average DTN times in the Neuro ED were 27 minutes compared to 65 minutes in the TED. Patients treated in the Neuro ED achieved DTN times of 45 min or less 87% of cases, while only 24% of the time in the TED. Patients treated in the Neuro ED achieved DTN times of 30 min or less 65% of cases, with only 4% of cases in the TED. Average DTCT times in the Neuro ED were 8 minutes faster than the TED. No differences in admission NIHSS were found with an average of 8.75, but a significant improvement was found in discharge NIHSS. Average discharge NIHSS was 3.8 for Neuro ED stroke patients compared with 5.6 for TED patients (p<0.001). Conclusion: Implementation of a Neuro ED led to swift management and improved symptoms for stroke patients. A dedicated Neuro ED is highly effective in improving DTN times, DTCT times, and overall stroke outcomes.

Malignant pleural mesothelioma represents a rare etiology of lung cancer metastasis to the brain. Neurologically symptomatic presentations are extremely rare as these metastatic lesions are detected in the late stages of the disease. Despite many highly heterogenous treatment techniques reported in the literature, overall survival is poor. A 72-year-old male with a history of mesothelioma presented with recurrent episodes of altered mental status, confusion and expressive aphasia. Imaging indicated a large hemorrhagic, enhancing lesion in the anterior left frontal lobe resulting in midline shift of 6 mm. He underwent a left frontal craniotomy for resection, after which he had complete resolution of symptoms. The resected mass was metastatic high-grade malignant mesothelioma. On a 1-month follow-up, new lesions in the bilateral frontal lobes were discovered, and despite undergoing adjuvant stereotactic radiosurgery, the right one grew significantly, causing notable mass effect. The patient successfully underwent a right craniotomy for resection.

Intradural spinal lipomas are extremely rare tumors, especially in the craniocervical junction. In a review of the literature, few articles share details on such cases and the best practices for clinical management of this pathology. In the following report, the authors present the case of a 62-year-old man who presented with acute onset dizziness and headache. A CT scan of the cervical spine revealed fatty tissue that was further confirmed by an MRI to be an intradural lipoma at C1-C2 level causing minimal mass effect on spinal cord without myelopathy or hydrocephalus. Therefore, the patient was treated conservatively through an appropriate course of medications with complete resolution of his symptoms.

Bocanegra-Becerra, Jhon E. MD*,‡,§; Patra, Devi P. MD§; Bathini, Abhijith MD§; Di Nome, Marie A. MD‖; Phelps, Taylor PA-C§; Nguyen, Brandon BA§,¶; Bendok, Bernard R. MD, MSCI*,‡,§,#,** Author Information

We present a case series of two patients who developed unilateral cranial nerve III (CNIII) palsy following non-aneurysmal SAH (NASAH). Subarachnoid hemorrhage (SAH) can present with various signs and symptoms. Early diagnosis is paramount to determine treatment course. Thus, clinicians must be aware of the variable clinical presentations of this condition. Two patients were admitted to a single institution for SAH. Patient 1, 52-year-old male, presented with headache, left eye ptosis, and painless diplopia. A non-contrast head computed tomography (CT) demonstrated a SAH within the left sylvian fissure and blood surrounding the mesencephalon and falx. Patient 2, 70-year-old male, presented with mild headache, acute onset of blurry vision, and right eye ptosis. A non-contrast head CT demonstrated a diffuse SAH predominantly in the Sylvian and suprasellar cisterns. Patients were admitted to the neuro intensive care unit and underwent diagnostic angiograms to identify possible aneurysms. Magnetic resonance imaging and angiograms for both patients were negative. Patients were managed with best medical therapy and followed up in the outpatient setting. Unilateral CNIII palsy in the setting of NASAH was identified in both patients. Diagnostic angiograms were negative for aneurysms; therefore, SAH were determined to be spontaneous. We propose that unilateral CNIII palsy is a possible sign of NASAH.

Acute myeloid leukemia (AML) accounts for 16% of all leukemias in children. Prognosis in the pediatric population is better than that of older populations, with a younger age at diagnosis being a favorable prognostic factor [1]. Diplopia is a rare first presenting sign of AML. We present a 15 year old male complaining of diplopia and unilateral orbital swelling. Workup in the emergency department found normal neuroimaging but revealed a markedly elevated leukocytosis with anemia and thrombocytopenia. Peripheral smear showed increased blast cells >10%. This patient was ultimately diagnosed with AML. This case demonstrates an atypical presentation of AML and urges a thorough work up for patients presenting with unexplained diplopia.

Spontaneous spinal epidural hematoma (SSEH) is a neurological condition that can lead to severe deficits if it is not properly diagnosed and surgically evacuated. Due to the rarity of the disease, few cases have been reported, and the etiology poorly understood; however, identifying the risk factors associated with SSEH can allow for both a swift and accurate diagnosis, as well as better health outcomes. Here, we present two cases of SSEH with stroke-like symptoms that occurred in the setting of hypertensive emergency and uncontrolled hypertension (210/112 and 181/117, respectively). MRI confirmed diagnoses of SSEH, and subsequent hemilaminectomies were performed, resulting in significant improvement of neurological function and discharge to outpatient rehabilitation. To the best of the authors' knowledge, we could only identify few other reports of SSEH attributed to uncontrolled hypertension. Considering that SSEH is an emergent condition requiring rapid diagnosis and surgical treatment, physicians should consider SSEH as a possible differential in hypertensive patients, particularly when presenting with stroke-like symptoms.

Flexible intramedullary nailing is gaining popularity as an effective method of treating long-bone fractures in children.We retrospectively reviewed the records and radiographs of 56 unstable fractures of the tibia in 54 children treated between March 1997 and May 2005. All were followed up for at least two months after the removal of the nails.Of the 56 tibial fractures, 13 were open. There were no nonunions. The mean time to clinical and radiological union was ten weeks. Complications included residual angulation of the tibia, leg-length discrepancy, deep infection and failures of fixation. All achieved an excellent functional outcome.We conclude that flexible intramedullary fixation is an easy and effective method of management of both open and closed unstable fractures of the tibia in children.

BACKGROUND Moyamoya disease is a condition with potentially devastating and permanent neurological sequelae. Adequate volume status and blood pressure, tight control of carbon dioxide to achieve normocarbia, and providing postoperative analgesia to prevent hyperventilation are typical goals that are used during anesthetic care in these patients. The purpose of this study was to assess postanesthesia neurological complications in moyamoya patients undergoing general anesthesia for imaging studies and surgical procedures excluding neurosurgical revascularization. METHODS We performed a retrospective cohort study examining moyamoya patients who received general anesthesia for imaging studies and nonneurosurgical-revascularization procedures between January 1, 2001 and December 1, 2016 at our quaternary care pediatric hospital. A general anesthetic encounter was excluded if it occurred within 30 days after a revascularization surgery. The electronic medical records of study patients were analyzed for perioperative management, and neurological outcomes within 30 days of an anesthetic were assessed. RESULTS A total of 58 patients undergoing 351 anesthesia exposures were included in the study. Three patients experienced neurological complications, which included focal neurological weakness, seizure, and altered mental status. The incidence of complications during anesthesia encounters was 0.85% (3/351) with a 95% confidence interval of 0.28-2.62. CONCLUSIONS Over a 16-year period at our hospital, 3 children with moyamoya disease who underwent anesthesia for nonneurosurgical-revascularization purposes demonstrated postanesthesia neurological symptoms. The symptoms were consistent with transient ischemic attacks and all resolved without long-term sequelae.

BACKGROUND:Vertebral osteomyelitis can be attributed to many factors including immunosuppression, diabetes, malignancy, collagen disease, periodontal disease, open fractures, and endoscopic procedures. Anaerobic bacteria, such as Veillonella species, are found in the oral cavity and are rarely implicated in the infection. This report describes vertebral osteomyelitis secondary to a dental abscess with positive Veillonella cultures.CASE DESCRIPTION:A 76-year-old man presented to the hospital due to back pain with a four-day history of fever and chills. CT scans revealed several abscesses in the lumbar region as well as indications of vertebral osteomyelitis. After a psoas drain, the patient began antibiotics with a combination of ampicillin-sulbactam, metronidazole, and levofloxacin, but due to the patient's penicillin allergy, he was initially desensitized to this antibiotic for a significant period of time. Laminectomies, foraminotomies, and facetectomies were performed, but the infection spread to vertebral levels. The patient was then switched to a combination of vancomycin, metronidazole, and levofloxacin which eliminated the infection. Final laminectomy was performed with posterior segmental instrumentation and arthrodesis. Post-operatively, there were no signs of infection. The patient recovered well and regained mobility. Deeper examination of the patient's medical history revealed a severe tooth abscess immediately before the onset of bacteremia.CONCLUSION:We believe that a delay in the onset of antibiotic treatment is what led to the initial bacteremia that ultimately took root in the lower lumbar vertebrae. To the best of our ability, we could identify only one other case that linked vertebral osteomyelitis to the oral cavity.

Hedayat, Hirad S MD; Gofman, Natalie; Bathini, Abhijith; Faber, Randall; Binning, Mandy J Author Information

The suprachiasmatic nucleus (SCN) is the neural network that drives daily rhythms in behavior and physiology. The SCN encodes environmental changes through the phasing of cellular rhythms across its anteroposterior axis, but it remains unknown what signaling mechanisms regulate clock function along this axis. Here we demonstrate that arginine vasopressin (AVP) signaling organizes the SCN into distinct anteroposterior domains. Spatial mapping of SCN gene expression using in situ hybridization delineated anterior and posterior domains for AVP signaling components, including complementary patterns of V1a and V1b expression that suggest different roles for these two AVP receptors. Similarly, anteroposterior patterning of transcripts involved in Vasoactive Intestinal Polypeptide- and Prokineticin2 signaling was evident across the SCN. Using bioluminescence imaging, we then revealed that inhibiting V1A and V1B signaling alters period and phase differentially along the anteroposterior SCN. V1 antagonism lengthened period the most in the anterior SCN, whereas changes in phase were largest in the posterior SCN. Further, separately antagonizing V1A and V1B signaling modulated SCN function in a manner that mapped onto anteroposterior expression patterns. Lastly, V1 antagonism influenced SCN period and phase along the dorsoventral axis, complementing effects on the anteroposterior axis. Together, these results indicate that AVP signaling modulates SCN period and phase in a spatially specific manner, which is expected to influence how the master clock interacts with downstream tissues and responds to environmental changes. More generally, we reveal anteroposterior asymmetry in neuropeptide signaling as a recurrent organizational motif that likely influences neural computations in the SCN clock network.

The suprachiasmatic nucleus (SCN) is the central circadian clock in mammals. It is entrained by light but resistant to temperature shifts that entrain peripheral clocks [1-5]. The SCN expresses many functionally important neuropeptides, including vasoactive intestinal peptide (VIP), which drives light entrainment, synchrony, and amplitude of SCN cellular clocks and organizes circadian behavior [5-16]. The transcription factor LHX1 drives SCN Vip expression, and cellular desynchrony in Lhx1-deficient SCN largely results from Vip loss [17, 18]. LHX1 regulates many genes other than Vip, yet activity rhythms in Lhx1-deficient mice are similar to Vip-/- mice under light-dark cycles and only somewhat worse in constant conditions. We suspected that LHX1 targets other than Vip have circadian functions overlooked in previous studies. In this study, we compared circadian sleep and temperature rhythms of Lhx1- and Vip-deficient mice and found loss of acute light control of sleep in Lhx1 but not Vip mutants. We also found loss of circadian resistance to fever in Lhx1 but not Vip mice, which was partially recapitulated by heat application to cultured Lhx1-deficient SCN. Having identified VIP-independent functions of LHX1, we mapped the VIP-independent transcriptional network downstream of LHX1 and a largely separable VIP-dependent transcriptional network. The VIP-independent network does not affect core clock amplitude and synchrony, unlike the VIP-dependent network. These studies identify Lhx1 as the first gene required for temperature resistance of the SCN clockworks and demonstrate that acute light control of sleep is routed through the SCN and its immediate output regions.