Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

Human vagus nerve branching in the cervical region

Background: Vagus nerve stimulation is increasingly applied to treat epilepsy, psychiatric conditions and potentially chronic heart failure. After implanting vagus nerve electrodes to the cervical vagus nerve, side effects such as voice alterations and dyspnea or missing therapeutic effects are observed at different frequencies. Cervical vagus nerve branching might partly be responsible for these effects. However, vagus nerve branching has not yet been described in the context of vagus nerve stimulation. Materials and methods: Branching of the cervical vagus nerve was investigated macroscopically in 35 body donors (66 cervical sides) in the carotid sheath. After X-ray imaging for determining the vertebral levels of cervical vagus nerve branching, samples were removed to confirm histologically the nerve and to calculate cervical vagus nerve diameters and cross-sections. Results: Cervical vagus nerve branching was observed in 29%of all cases (26% unilaterally, 3% bilaterally) and proven histologically in all cases. Right-sided branching (22%) was more common than left-sided branching (12%) and occurred on the level of the fourth and fifth vertebra on the left and on the level of the second to fifth vertebra on the right side. Vagus nerves without branching were significantly larger than vagus nerves with branches, concerning their diameters (4.79mm vs. 3.78mm) and cross-sections (7.24 mm2 vs. 5.28mm2). Discussion: Cervical vagus nerve branching is considerably more frequent than described previously. The side-dependent differences of vagus nerve branching may be linked to the asymmetric effects of the vagus nerve. Cervical vagus nerve branching should be taken into account when identifying main trunk of the vagus nerve for implanting electrodes to minimize potential side effects or lacking therapeutic benefits of vagus nerve stimulation

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

X-rays obtained from the cervical spine of a 69 year-old male in the anterior-posterior (3a) and in the lateral projection (3b).

<p>Metal needles indicate the most cranial and caudal part of the vagus nerve that could be visualized with the surgical approach to the carotid triangle. d = dorsal, l = left, r = right, v = ventral; scale bar = 10 mm.</p

Images taken during dissection of the cervical vagus nerve (CVN) in the carotid sheath.

<p>Fig. 1a shows a left-sided CVN without branching and Fig. 1c-d CVN with branches on the left side (1b) or on the right side (1c,d). Arrows indicate the branches. C = (common or internal) carotid artery, J = internal jugular vein, O = superior venter of the omohyoideus muscle; cd = caudal, cr = cranial, m = medial, l = lateral; scale bar = 15 mm (a,b), 12 mm (c,d).</p

Baseline characteristics such as donors’ age and gender are given and the extent to which the vagus nerve could be visualized in vertebral segments.

<p>Baseline characteristics such as donors’ age and gender are given and the extent to which the vagus nerve could be visualized in vertebral segments.</p

X-rays obtained from the cervical spine of a 69 year-old male in the anterior-posterior (3a) and in the lateral projection (3b).

<p>Metal needles indicate the most cranial and caudal part of the vagus nerve that could be visualized with the surgical approach to the carotid triangle. d = dorsal, l = left, r = right, v = ventral; scale bar = 10 mm.</p

Delayed Stroke after Aneurysm Treatment with Flow Diverters in Small Cerebral Vessels: A Potentially Critical Complication Caused by Subacute Vasospasm

Flow diversion (FD) is a novel endovascular technique based on the profound alteration of cerebrovascular hemodynamics, which emerged as a promising minimally invasive therapy for intracranial aneurysms. However, delayed post-procedural stroke remains an unexplained concern. A consistent follow-up-regimen has not yet been defined, but is required urgently to clarify the underlying cause of delayed ischemia. In the last two years, 223 patients were treated with six different FD devices in our center. We identified subacute, FD-induced segmental vasospasm (SV) in 36 patients as a yet unknown, delayed-type reaction potentially compromising brain perfusion to a critical level. Furthermore, 86% of all patients revealed significant SV approximately four weeks after treatment. In addition, 56% had SV with 25% stenosis, and 80% had additional neointimal hyperplasia. Only 13% exhibited SV-related high-grade stenosis. One of those suffered stroke due to prolonged SV, requiring neurocritical care and repeated intra-arterial (i.a.) biochemical angioplasty for seven days to prevent territorial infarction. Five patients suffered newly manifested, transient hemicrania accompanying a compensatorily increased ipsilateral leptomeningeal perfusion. One treated vessel obliterated permanently. Hence, FD-induced SV is a frequent vascular reaction after FD treatment, potentially causing symptomatic ischemia or even stroke, approximately one month post procedure. A specifically early follow-up-strategy must be applied to identify patients at risk for ischemia, requiring intensified monitoring and potentially anti-vasospastic treatment

Hematoxylin-eosin stained histology samples obtained from the vagus nerve (2a) and from a vagus nerve branch (2b) for evaluating the existence of nerve fibers.

<p>A = arterial branch from the inferior thyroid artery, E = epineurium; scale bar = 500 μm.</p

Statistical comparison of vagus nerve diameters and cross-sections (mean value ± standard deviation).

<p>Statistical comparison of vagus nerve diameters and cross-sections (mean value ± standard deviation).</p