Effects of Photobiomodulation on Changes in Cognitive Function and Regional Cerebral Blood Flow in Patients with Mild Cognitive Impairment: A Pilot Uncontrolled Trial.

BACKGROUND: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. OBJECTIVE: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. METHODS: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. RESULTS: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. CONCLUSION: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.

Endovascular Treatment of Carotid Blowout Syndrome.

BACKGROUND: Carotid blowout syndrome (CBS) is a life-threatening disease characterized by compromise of the carotid artery by head and neck cancer (HNC). MATERIALS AND METHODS: We reviewed the characteristics and outcomes of all patients with carotid blowout syndrome who were treated between April 2010 and December 2019. Twelve patients with a history of HNC and radiation therapy were investigated. The balloon occlusion test (BOT) was performed in all patients to confirm collateral circulation. We placed a stent in patients who were intolerant to the BOT. RESULTS: The patients' ages ranged from 50 to 81 years (mean: 68.1 years). Therapeutic occlusion of the affected internal carotid artery was performed in nine patients, while stenting was performed in three patients. Immediate hemostasis was achieved in all patients. Patients treated using stents were administered perioperative DAPT. One patient experienced rebleeding after surgery. Two patients had procedure-related cerebral infarctions. One patient died, but the others survived without major neurological deficits. One patient had persistent aneurysm after surgery that resolved over time. CONCLUSION: Endovascular treatment via occlusion or stent-based reconstruction of the internal carotid artery resulted in immediate hemostasis. Carotid occlusion and covered stent application are safe and efficient techniques to treat CBS secondary to HNC. Surgeons may obtain better outcomes if they perform BOT before occlusion and design treatment accordingly.

Higher Risk for Reintervention in Patients after Stenting for Radiation-Induced Internal Carotid Artery Stenosis: A Single-Center Analysis and Systematic Review.

BACKGROUND: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS). METHODS: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS. RESULTS: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12). CONCLUSIONS: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.

Radiation-induced vascular changes in the intracranial irradiation field in medulloblastoma survivors: An MRI study.

BACKGROUND AND PURPOSE: While survival times after treatment of medulloblastoma are increasing, little is known about radiochemotherapy (RCT)-induced cerebrovascular changes. High resolution vessel wall imaging (VWI) sequences are an emerging tool for the evaluation of cerebrovascular diseases. We performed VWI in medulloblastoma long-term survivors to screen for late sequelae of RCT. MATERIAL AND METHODS: Twenty-two pediatric medulloblastoma survivors (mean age 25.8 years (10-53 years); 16.3 years (mean) post primary RCT (range 1-45 years)) underwent 2D VWI-MRI. Vessel wall thickening, contrast enhancement and luminal narrowing were analyzed. The findings were correlated with the patients' radiation protocols. RESULTS: Vessel wall changes were observed the intracranial internal carotid artery (ICA) and the vertebrobasilar circulation (VBC) in 14 of 22 patients (63.6%). In multivariate analysis, time after RCT (OR = 1.38, p < 0.05) was strongest independent predictor for development of vessel wall alterations. The dose of radiation was not a relevant predictor. CONCLUSIONS: With longer follow-up time intracranial vessel wall changes are observed more frequently in medulloblastoma survivors. Thus VWI is a useful tool to monitor vessel wall alterations of cranially irradiated patients, creating the prerequisite for further treatment of late sequelae.

Pathologic Findings of Symptomatic Carotid Artery Stenosis Several Decades after Radiation Therapy: A Case Report.

Improved long-term survival of malignancy has drawn increased attention to late cerebrovascular toxicity after neck radiotherapy. Recently, neck radiotherapy has been found as a significant risk factor of carotid artery stenosis and ischemic stroke; however, long-term adverse effects of radiation in large arteries remain unknown. Here, we described an autopsied case with recurrent ischemic stroke associated with ipsilateral carotid artery stenosis several decades after neck radiation therapy. Pathologically, there were intima-media fibrosis, endothelial cell loss, and decreased expression of thrombomodulin in irradiated carotid artery stenosis. Our findings support the hypothesis that long-term radiation-induced vascular injury in large arteries is morphologically different from atherosclerotic change. Furthermore, endothelial cell injury may promote fibrin thrombus formation through decreased expression of thrombomodulin, which may cause ischemic stroke associated with radiation-induced carotid artery stenosis.

Simulation study of high-dose-rate brachytherapy for early glottic cancer.

PURPOSE: External beam radiation therapy (EBRT) is effective for early glottic cancers, with cure rates of ∼90% for T1 tumors. EBRT has strengths but also disadvantages including radiation to healthy tissues and duration of 5-7 weeks. With advances in laryngeal framework surgery, new devices can provide reliable, minimally invasive access to the larynx. Such devices could be modified to insert brachytherapy catheters. Brachytherapy could provide focused radiation while limiting dose to normal structures in the larynx and neck. As a preliminary step, we performed simulations comparing EBRT to high-dose-rate brachytherapy to assess if this approach could provide dosimetric advantage. METHODS AND MATERIALS: One- and 2-catheter brachytherapy simulations were performed for 3 patients with T1 glottic carcinoma. Percentage of dose delivered to the target and adjacent structures was compared with conventional EBRT using 3D and intensity-modulated radiation therapy approaches. RESULTS: Percentage of structures exposed to 50% of the dose was lower for brachytherapy compared with 3D EBRT and intensity-modulated radiation therapy, particularly for the cricoid and contralateral arytenoid. Dose was also lower for the carotid-internal jugular vein complexes compared with 3D EBRT. Dose profiles did not differ significantly between 1- and 2-catheter simulations. CONCLUSION: Brachytherapy can decrease radiation to normal tissues including laryngeal cartilages and carotid-internal jugular vein complexes. Recent advancements allowing catheter placement may afford the potential to decrease radiation to healthy tissues with decreased treatment time. However, careful, stepwise evaluation of feasibility and outcomes in model systems is required before recommending this approach for such high cure rate cancers in humans.

Effects of neck radiation therapy on extra-cranial carotid arteries atherosclerosis disease prevalence: systematic review and a meta-analysis.

INTRODUCTION: Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli. AIM: To evaluate the effect of radiation therapy on ECCA atherosclerosis progression. METHODS: Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT. RESULTS: Eight studies were included in the final analysis with total of 1070 patients - 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001). CONCLUSION: The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT.

Carotid blowout syndrome: endovascular management of acute hemorrhage with tapering overlapped covered stents.

Carotid blowout is a rare fatal complication most commonly observed in head and neck cancer patients, especially after radiation therapy. Traditional surgical approaches carry extremely high morbidity and mortality rates. We present a case of acute hemorrhage from extracranial carotid artery in a 64-year-old man with history of total laryngectomy, tracheostomy, and chemoradiotherapy for laryngeal cancer. Tumor was noted to be encasing and eroding into the internal and common carotid artery with a large soft tissue neck defect. Hemorrhage was successfully controlled employing 3 Viabahn covered stents of increasing diameter in the internal and common carotid artery in an overlapping fashion under local anesthesia. Deployment of tapering overlapped covered stents in common and internal carotid artery may safely be performed to obtain endovascular control of active hemorrhage in a hostile neck.

Cavernous internal carotid artery aneurysm after radiotherapy presenting with external ophthalmoplegia.

Cranial radiotherapy could cause several types of vasculopathies, which include atherosclerotic occlusive diseases, moyamoya disease, and aneurysm formation. To our knowledge, radiation-induced aneurysms of the internal carotid artery (ICA) are extremely rare. Here, we report a 68-year-old woman who presented with external ophthalmoplegia caused by radiotherapy after the transsphenoidal surgery for metastastic tumor of the clivus region, and the angiography demonstrated a giant aneurysm of the cavernous ICA. After the ICA ligation, the patient recovered well without brain ischemia with a 6-month-long follow-up. The present case is extremely rare with external opthalmoplegia caused by the giant cavernous ICA aneurysm, and the radiotherapy after transsphenoidal surgery might have been critical in the formation of the aneurysm.

[Rupture of an internal carotid artery pseudoaneurysm after irradiation for a nasopharyngeal carcinoma--case report].

The primary treatment of nasopharyngeal carcinoma (NPC) has been external radiotherapy. Rupture of an internal carotid artery (ICA) pseudoaneurysm is a rare complication of irradiation therapy for a nasopharyngeal carcinoma. A 78 years old man had a history of NPC treated with radiotherapy in 1993. He was admitted to the hospital because of epistaxis. Angiography showed an ICA pseudoaneurysm pointing medially to the nasopharynx. Coil embolization of the ICA was performed, but cerebral infarction occurred. Internal carotid artery (ICA) pseudoaneurysms are an uncommon but potentially lethal condition. Angiography is the mainstay of diagnosis of the aneurysm and planning the embolization of the ICA. We should be more aware of this complication in NPC patients.

Carotid stenosis after adjuvant cervical radiotherapy in patients with head and neck cancers: a prospective controlled study.

OBJECTIVES: To determine the prevalence of radiation-induced carotid stenosis, in patients who were treated for head and neck malignancies, using colour-flow duplex scanning. DESIGN: Prospective controlled study at a single medical centre. PARTICIPANTS: We enrolled two groups of patients. The first (radiotherapy group) consisted of patients who received surgical treatment and adjuvant radiotherapy of the neck. The control group consisted of patients with head and neck malignancies who received only surgical treatment. MAIN OUTCOME MEASURES: All patients were evaluated with carotid artery ecoDoppler imaging 1 week before and 36 months after the surgical procedure. Intima-media thickness was measured bilaterally at the internal carotid artery and at the bifurcation. Carotid obstruction was classified as low (0-30%), moderate (31-49%) or severe (≥50%). RESULTS: The preoperative stenosis grade did not differ between groups. In 15/25 patients (60%) in the radiotherapy group, mild stenosis evolved to moderate stenosis, while only 6/37 (16%) of the controls did (P = 0.004). Additionally, 9/39 (23%) patients in the radiotherapy group progressed to severe stenosis compared with only 3/54 (6%) controls (P = 0.029). The overall evolution showed that stenosis worsened in 24/32 (62%) patients in the radiotherapy group and 9/54 (17%) patients in the control groups (P < 0.0001). CONCLUSIONS: These results highlight the need to study the long-term incidence of cerebrovascular events in these two different populations (radiation treated and surgically treated) to identify increased cerebrovascular morbidity.

A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN) were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT) and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs), internal carotid arteries (ICAs) and basal artery (BA) were estimated through Transcranial Color Doppler (TCD). The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05). IMT had positive correlation with post radiation interval (p = 0.049). Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001). Plaques were more common in patients with TLN than patients without TLN (p = 0.038). In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001). Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001). CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

Carotid tortuosity in patients with prior cervical radiation: increased technical challenge during carotid stenting.

INTRODUCTION: Anatomic distortion associated with radiation-induced tissue changes may pose challenges for patients with prior cervical irradiation undergoing carotid stenting. We sought to evaluate the effect of these changes on carotid intervention. METHODS: Carotid angioplasty and stenting (CAS) for high-grade stenosis was performed in 203 patients. In all, 12 consecutive patients with prior ipsilateral cervical irradiation were age-/sex-matched to 24 controls. Degree of internal carotid (IC) tortuosity was assessed by 4 methods: (a) deviation of IC from common carotid (CCA) axis, (b) number of intersections between this axis and the course of the IC, (c) total degrees of angulation along the course of the extracranial IC, and (d) the IC length to straight-line distance ratio. RESULTS: Carotid angioplasty and stenting was successful in all patients. Mean age was 72.8 ± 10 years; 58.4% were male. Twenty-nine percent were symptomatic (14.4% transient ischemic attack [TIA], 8.5% cardiovascular accident [CVA], and 6.5% amaurosis). Comorbidities were similar between the entire cohort and the subgroups of irradiated/control patients. The IC revealed a higher degree of deviation from the axis of the CCA in the previously irradiated patients compared to those without radiation (29.2° ± 4.5° vs 13.0° ± 2.0°, P = .001) and was more likely to intersect this axis in those with a history of cervical irradiation (83.3% vs 14.3%, P < .05). Irradiated patients also exhibited a significantly greater degree of tortuosity versus nonirradiated patients when assessed by total angulation along the course of the carotid (171.8° ± 26.0° vs 74.2° ± 20.2°, P = .014) and by the IC length:distance ratio (1.14 ± 0.05 vs 1.04 ± 0.03, P = .020). Despite increased IC tortuosity in patients with prior irradiation, all procedures were successfully completed and there did not appear to be a predilection for a specific filter type. CONCLUSIONS: A history of cervical irradiation is associated with increased tortuosity of the IC, leading to potential challenges for filter and stent deployment. However, this increased procedural complexity did not affect technical success rate or device selection in this series.

Nontraumatic and postirradiated intracavernous carotid hemorrhage: an unusual case of epistaxis and review of the literature.

Intracavernous carotid hemorrhage is a rare cause of epistaxis. We present a case of epistaxis caused by postradiotherapy and nontraumatic cavernous internal carotid artery (ICA) hemorrhage. An 80-year-old man was admitted to our hospital with a one week history of recurrent left-sided epistaxis and a past history of radiotherapy after radical maxillectomy. Emergent angiography revealed a leak in the cavernous segment of the ICA and subsequent detachable balloon occlusion embolization of the left internal carotid artery was performed without sequelae. We conclude that carotid artery hemorrhage must be considered in the differential diagnosis of profuse and recurrent epistaxis, especially for patients after craniofacial radiotherapy. ICA embolization is the definitive treatment provided cross circulation is adequate.

Radiation-associated carotid artery atherosclerosis: case report and review of contemporaneous literature.

Radiation therapy (RT) is a component of the treatment of patients with head and neck malignancies. This therapy may damage the nearby carotid arteries, thereby initiating or accelerating the atherosclerotic process (atheroma formation). Dentists treating patients who have been irradiated should examine the patient's panoramic radiograph for evidence of atheroma-like calcifications, which appear 1.5 to 2.5 cm posterior and inferior to the angle of the mandible. Patients with evidence of such lesions should be referred to their primary care physician with the suggestion that an ultrasound examination of the carotid arteries is indicated.

Radiation carotid blowout syndrome in nasopharyngeal carcinoma: angiographic features and endovascular management.

OBJECTIVE: To report clinical manifestations, angiographic features, and outcomes of endovascular management in 14 patients with 15 radiation carotid blowout syndromes of nasopharyngeal carcinomas. STUDY DESIGN AND SUBJECTS: Retrospective chart review of 14 patients with nasopharyngeal carcinomas (mean age 49 years) with 15 radiation carotid blowout syndromes who had undergone endovascular embolization to manage oronasal bleeding in the past 10 years. RESULTS: Average radiation dose to affected carotid artery was 73 gray units (latent period: 33 months). Radiation carotid blowout syndrome was detected in internal (n = 10), external (n = 4), or common carotid artery (n = 1). Detachable balloons were used in 11 affecting arteries for vascular occlusion; 4 were treated by liquid adhesives or coil. Endovascular treatment was successful in all 15 radiation carotid blowout syndromes with cessation of hemorrhage. One patient had hemiparesis after embolization. Mean clinical follow-up was 21 months. CONCLUSION: Radiation carotid blowout syndrome in nasopharyngeal carcinoma may occur in various periods or arteries. Endovascular embolization provides both safe and effective management.

Internal carotid occlusion following gamma knife radiosurgery for cavernous sinus meningioma.

Gamma knife radiosurgery is a safe and effective treatment for cavernous sinus meningioma, associated with a very low morbidity. However, a high dose of radiation could lead to modifications of the vascular wall such as in radiosurgical treatment of arteriovenous malformations. We present a patient treated by gamma knife radiosurgery for a left cavernous sinus meningioma using a margin dose of 13 Gy at the 50% isodose. A complete occlusion of the intracavernous segment of the ICA occurred during the follow-up, in combination with a regression of the meningioma volume. The patient sustained no neurological deficit. We found that a hot spot of dose was administered to the intracavernous segment of the internal carotid artery, with a maximum dose of 22.3 Gy. Dose heterogeneity inside the target volume can produce hot spots of dose inside the internal carotid artery that can lead to a vascular occlusion. Therefore, we recommend shifting the hot spot during the dosimetry planning in order to reduce the incidence of such vascular injury.