Workup of Noncerebral Systemic Arterial Embolic Source. A meta-analysis of 7 studies showed that delayed contrast-enhanced cardiac MR had a pooled sensitivity of 100% and a specificity of 99% for detecting left atrial and left atrial appendage thrombus in patients with atrial fibrillation [45]. In another meta-analysis, there was no significant difference in sensitivity and specificity between cardiac CT and cardiac MR in the detection of left atrial appendage thrombus [29]. Contrast- enhanced cardiac MR had a sensitivity of 88% and a specificity of 99% compared to surgical or pathological 9 Workup of Noncerebral Systemic Arterial Embolic Source confirmation of left ventricular thrombus [46]. Cardiac MR is also an accurate imaging modality for the evaluation of valvular disease, including aortic and mitral valve vegetations, which can dislodge and result in arterial embolism [37,47]. Additionally, cardiac MR offers detailed soft tissue characterization for the analysis of benign and malignant intracardiac neoplasms [39,48]. MRI Heart Function and Morphology Without IV Contrast Cardiac MR without contrast provides a detailed anatomic evaluation of the heart chambers. In the workup of embolic sources, the primary role of cardiac MR is in the identification of intracardiac thrombus. A meta-analysis of 7 studies showed that cine cardiac MR had a pooled sensitivity of 91% and a specificity of 93% for detecting left atrial and left atrial appendage thrombus in patients with atrial fibrillation [45]. Furthermore, cine cardiac MR had an 82% sensitivity and a 100% specificity in detecting left ventricle thrombus in postmyocardial infarction patients compared with a standard delayed enhancement cardiac MR [49]. Cardiac MR without contrast is also capable of identifying valvular pathology and cardiac neoplasms, although data on its applicability in the setting of systemic arterial embolism are lacking.


Workup of Noncerebral Systemic Arterial Embolic Source. US Duplex Doppler Abdomen There is no relevant literature to support the use of Doppler US of the abdomen as an initial imaging modality in the evaluation of the source of known embolic lower extremity arterial occlusion. However, some imaging protocols may include limited views of the abdominal aorta, which may detect intraluminal aortic thrombus or significant atherosclerotic disease [56]. US Echocardiography Transesophageal TEE is an invasive diagnostic study with the ability to detect cardiac pathology predisposed to embolism. TEE has a sensitivity of 93% to 100% and a specificity of 95% to 99% for detecting left atrial appendage thrombus when compared to intraoperative findings [31,50,51]. Furthermore, TEE can evaluate left ventricular systolic dysfunction, spontaneous echo contrast, slow left atrial appendage peak flow velocities, and complex left atrial appendage morphologies, which are all associated with left atrial thrombus and thromboembolic risk [2,4]. In addition, TEE can detect left ventricular thrombus, with 1 study reporting a 40% sensitivity and a 96% specificity for the modality compared to findings at surgery or pathology [46]. Proximal aortic thrombus can also be assessed using TEE, although evaluation is limited by blind spots (distal ascending aorta and proximal aortic arch) owing to air in the trachea [10,13]. Detection of valvular disease and intracardiac neoplasms can also be accomplished with TEE. US Echocardiography Transthoracic Resting TTE is a noninvasive imaging modality capable of detecting cardiac pathology susceptible to embolism. TTE is inferior to TEE in the assessment of left atrial appendage thrombus because the transducer is distant from the left atrium when placed on the chest [52]. In 1 study, a cardiac embolic source was detected by TEE in about 40% of patients with normal TTE [53]. In another study, a cardiac embolic source was identified by TTE in 15% of the study group compared with 57% by TEE [54].


Workup of Noncerebral Systemic Arterial Embolic Source. Sensitivity and specificity were 23% and 96%, respectively, for the detection of left ventricular thrombus compared to findings at surgery or pathology [46]. In the detection of left ventricle thrombus, contrast-enhanced TTE had a 64% sensitivity and a 99% specificity compared to a delayed enhancement cardiac MR standard [49]. TTE can also be applied for the diagnosis of valvular disease and cardiac neoplasms. There is no evidence to support the use of TTE in the evaluation of aortic thrombus. Variant 4: Known multiorgan system arterial occlusions. Suspected embolic etiology. Next imaging study to determine source. The variant assumes that multiorgan arterial occlusions have already been established. Typically, these diagnoses are made by CTA, arteriography, or MRA, although the clinical examination or another imaging study could also be used. CT Heart Function and Morphology With IV Contrast The primary role of cardiac CT in the initial evaluation of multiorgan system arterial embolic occlusion is in the workup of cardiac thrombus as a source. Multiple studies have established high rates of atrial thrombus detection by cardiac CT compared to TEE [18-27]. Meta-analyses have found sensitivities of 96% to 99% and specificities of 92% to 94% for detection of left atrial or left atrial appendage thrombus with cardiac CT compared to a TEE reference standard [28-30]. When compared with intraoperative findings, cardiac CT was 100% sensitive and 85% specific for finding left atrial thrombus [31]. Complex left atrial appendage morphologies, which predispose to thrombus formation, can also be characterized by cardiac CT [32-34]. Additionally, cardiac CT can differentiate left ventricular thrombus from the myocardial wall, with 1 study demonstrating a sensitivity, specificity, and 10 Workup of Noncerebral Systemic Arterial Embolic Source positive and negative predictive values of 94%, 97%, 94%, and 97%, respectively [35].


Workup of Noncerebral Systemic Arterial Embolic Source. Studies have also demonstrated cardiac CT to have comparable accuracy to TEE for identification of vegetations in the setting of infective endocarditis, another potential source of arterial embolism [36-38]. Cardiac CT can identify cardiac neoplasms, both benign and malignant, which have the potential to shed and embolize to distal arterial beds [39,40]. CTA Chest With IV Contrast In some conditions or clinical scenarios, there may be a high suspicion that the embolic source is in the thoracic aorta, and a CTA limited to the chest may be diagnostic. As such, multidetector chest CTA with IV contrast can be used to evaluate for at-risk atherosclerotic plaque or the presence of thrombus in the thoracic aorta. CTA is useful in the assessment of the size, extent, and location of an embolic source in the aorta, which can aid in management decisions [13,41]. A number of small studies have used chest CTA to detect aortic mural thrombus that was suspected of embolization [1,12-14,42]. Specific data on the sensitivity and specificity of this imaging modality are lacking. CTA Chest, Abdomen, and Pelvis With IV contrast Multidetector CTA with IV contrast can be used to evaluate for the presence of at-risk atherosclerotic plaque or thrombus in the aorta in its entirety. CTA is useful in the assessment of the size, extent, and location of an embolic source in the aorta, which can aid in management decisions [13,41]. Aortic intraluminal thrombus is oftentimes associated with aneurysm, particularly in the abdomen, which is readily detected by CTA [56,57]. A number of small studies have used CTA to detect aortic mural thrombus that was suspected of embolization [1,12-14,42]. Specific data on the sensitivity and specificity of this imaging modality are lacking. MRA Chest Without and With IV Contrast In some conditions or clinical scenarios, there may be a high suspicion that the embolic source is in the thoracic aorta and an MRA limited to the chest may be diagnostic.


Workup of Noncerebral Systemic Arterial Embolic Source. In 1 study, detection of thoracic aorta pathology by contrast-enhanced chest MRA was equivalent in sensitivity, specificity, and diagnostic accuracy compared to noncontrast MRA, although only a single case of thrombus was included in the analysis [43]. On the other hand, in a small analysis which included 9 patients with aortic thrombus, contrast-enhanced MRA had a lower thrombus detection rate compared to a noncontrast examination, although this finding was not statistically significant [44]. Data comparing MRA of the chest to other imaging modalities are lacking. MRA Chest Without IV Contrast In some conditions or clinical scenarios, there may be a high suspicion that the embolic source is in the thoracic aorta and an MRA limited to the chest may be diagnostic. One small study found this examination to have a higher detection rate for aortic thrombus when compared with contrast-enhanced MRA, although the difference was not statistically significant [44]. In another study, sensitivity, specificity, and diagnostic accuracy of unenhanced steady- state free precession MRA were 100% for the detection of thoracic aorta pathology compared to a contrast-enhanced MRA reference standard; however, this analysis only included 1 case of mural thrombus [43]. Data comparing MRA of the chest to other imaging modalities is lacking. MRA Chest, Abdomen, and Pelvis Without and With IV Contrast MRA of the chest, abdomen, and pelvis without and with IV contrast can be used to evaluate for the presence of an embolic source in the aorta in its entirety. In 1 study, detection of thoracic aorta pathology by contrast-enhanced chest MRA was equivalent in sensitivity, specificity, and diagnostic accuracy compared to noncontrast MRA, although only a single case of thrombus was included in the analysis [43].


Workup of Noncerebral Systemic Arterial Embolic Source. On the other hand, in a small analysis which included 9 patients with aortic thrombus, contrast-enhanced MRA had a lower thrombus detection rate compared to a noncontrast examination, although this finding was not statistically significant [44]. Contrast- enhanced MRA of the abdomen has been used for intraluminal thrombus detection in the setting of aneurysms, although comparative data is insufficient [56-58]. Data comparing MRA of the chest, abdomen, and pelvis to other imaging modalities is lacking. MRA Chest, Abdomen, and Pelvis Without IV Contrast Chest, abdomen, and pelvis MRA without IV contrast can be used to evaluate for the presence of an embolic source in the aorta in its entirety. One small study found this examination to have a higher detection rate for aortic thrombus when compared with contrast-enhanced MRA, although the difference was not statistically significant [44]. In another study, sensitivity, specificity, and diagnostic accuracy of unenhanced steady-state free precession MRA were 100% for the detection of thoracic aorta pathology compared to a contrast-enhanced MRA reference standard, however this analysis only included 1 case of mural thrombus [43]. Noncontrast MRA has been used for the 11 Workup of Noncerebral Systemic Arterial Embolic Source detection of abdominal aortic intraluminal thrombus, although there is insufficient data comparing it to contrast- enhanced MRA [56-58]. Data comparing MRA of the chest, abdomen, and pelvis to other imaging modalities is lacking. MRI Heart Function and Morphology Without and With IV Contrast Cardiac MR is a noninvasive imaging study that can reliably detect intracardiac thrombus as well as valvular and neoplastic pathologies. A meta-analysis of 7 studies showed that delayed contrast-enhanced cardiac MR had a pooled sensitivity of 100% and a specificity of 99% for detecting left atrial and left atrial appendage thrombus in patients with atrial fibrillation [45].


Workup of Noncerebral Systemic Arterial Embolic Source. In another meta-analysis, there was no significant difference in sensitivity and specificity between cardiac CT and cardiac MR in the detection of left atrial appendage thrombus [29]. Contrast- enhanced cardiac MR had a sensitivity of 88% and a specificity of 99% compared to surgical or pathological confirmation of left ventricular thrombus [46]. Cardiac MR is also an accurate imaging modality for the evaluation of valvular disease, including aortic and mitral valve vegetations, which can dislodge and result in arterial embolism [37,47]. Additionally, cardiac MR offers detailed soft tissue characterization for the analysis of benign and malignant intracardiac neoplasms [39,48]. MRI Heart Function and Morphology Without IV Contrast Cardiac MR without contrast provides a detailed anatomic evaluation of the heart chambers. In the workup of embolic sources, the primary role of cardiac MR is in the identification of intracardiac thrombus. A meta-analysis of 7 studies showed that cine cardiac MR had a pooled sensitivity of 91% and a specificity of 93% for detecting left atrial and left atrial appendage thrombus in patients with atrial fibrillation [45]. Furthermore, cine cardiac MR had an 82% sensitivity and a 100% specificity in detecting left ventricle thrombus in postmyocardial infarction patients compared with a standard delayed enhancement cardiac MR [49]. Cardiac MR without contrast is also capable of identifying valvular pathology and cardiac neoplasms, although data on its applicability in the setting of systemic arterial thromboembolism are lacking. US Duplex Doppler Abdomen There is no relevant literature to support the use of Doppler US of the abdomen as an initial imaging modality in the evaluation of the source of known embolic multiorgan arterial occlusion. However, some imaging protocols may include limited views of the abdominal aorta, which may detect intraluminal aortic thrombus or significant atherosclerotic disease [56].


Workup of Noncerebral Systemic Arterial Embolic Source. US Echocardiography Transesophageal TEE is an invasive diagnostic study with the ability to detect cardiac pathology predisposed to embolism. TEE has a sensitivity of 93% to 100% and a specificity of 95% to 99% for detecting left atrial appendage thrombus when compared with intraoperative findings [31,50,51]. Furthermore, TEE can evaluate left ventricular systolic dysfunction, spontaneous echo contrast, slow left atrial appendage peak flow velocities, and complex left atrial appendage morphologies, which are all associated with left atrial thrombus and thromboembolic risk [2,4]. In addition, TEE can detect left ventricular thrombus with 1 study reporting a 40% sensitivity and a 96% specificity for the modality compared to findings at surgery or pathology [46]. Proximal aortic thrombus can also be assessed using TEE, although evaluation is limited by blind spots (distal ascending aorta and proximal aortic arch) owing to air in the trachea [10,13]. Detection of valvular disease and intracardiac neoplasms can also be accomplished with TEE. US Echocardiography Transthoracic Resting TTE is a noninvasive imaging modality capable of detecting cardiac pathology susceptible to embolism. TTE is inferior to TEE in the assessment of left atrial appendage thrombus because the transducer is distant from the left atrium when placed on the chest [52]. In 1 study, a cardiac embolic source was detected by TEE in about 40% of patients with normal TTE [53]. In another study, a cardiac embolic source was identified by TTE in 15% of the study group compared with 57% by TEE [54]. Sensitivity and specificity were 23% and 96%, respectively, for the detection of left ventricular thrombus compared to findings at surgery or pathology [46]. In the detection of left ventricle thrombus, contrast-enhanced TTE had a 64% sensitivity and a 99% specificity compared to a delayed enhancement cardiac MR standard [49].


Cranial Neuropathy

Cranial Neuropathy.  Introduction/Background The human body has 12 paired cranial nerves (CNs) that provide specialized sensory and motor innervation to the head and neck region. As a group, the CNs have both sensory and motor components similar to those of the spinal nerves. Individually the CNs may be purely sensory, purely motor, or a mixture of both sensory and motor. Functions of the CNs may be divided into three sensory and three motor categories. The sensory group includes visceral sensory, which supplies sensory input from the internal organs; general sensory, which supplies tactile, pain, temperature, and other sensations; and special sensory, which includes the special senses of smell, vision, taste, hearing, and balance. Of the three motor functions, somatic motor nerves innervate muscles that develop from the body somites; branchial motor nerves innervate muscles derived from the branchial arches; and visceral motor nerves innervate the viscera, glands, and smooth muscle [1-4]. The CNs emerge in an orderly fashion from the rostral portion of the embryologically developing neural tube, which develops to form the brain. Anatomically, the 12 pairs of CNs are designated by numbers I-XII. The CNs include the olfactory (CN I), optic (CN II), oculomotor (CN III), trochlear (CN IV), trigeminal (CN V), abducens (CN VI), facial (CN VII), vestibulocochlear (CN VIII), glossopharyngeal (CN IX), vagus (CN X), spinal accessory (CN XI), and hypoglossal (CN XII) nerves. The olfactory (CN I) and optic (CN II) nerves are actually tracts formed from the telencephalon and diencephalon, respectively, and are not considered true nerves [4,5]. The CN nuclei arise in the brainstem, largely topologically arranged between the midbrain and the rostral cervical spine (CN XI). Current knowledge of CN anatomy has been improved by modern microsurgical techniques and endoscopic dissections, allowing visualization of the CN brainstem exit zones [3,4,6-13].


Cranial Neuropathy

Cranial Neuropathy. Various nomenclatures for the segments of the CNs are described in the anatomical, surgical, and radiological literature [5,14,15]. In approaching cranial neuropathy, several concepts should be emphasized: 1. Cranial neuropathy can result from pathology affecting the nerve fibers at any point from the CN nucleus to the end organ supplied by the nerve. Pathologic processes affecting the brain, CN nuclei, or nerve fiber tracts supplying CNs are often associated with multiple neurologic symptoms. The CNs may take long, circuitous routes to their end organs. A detailed knowledge of CN anatomy coupled with a careful neurologic examination is essential for proper clinical localization of potential lesions and for the selection of appropriate imaging protocols. aMayo Clinic Arizona, Phoenix, Arizona. bPanel Chair, University of Iowa Hospitals and Clinics, Iowa City, Iowa. cPanel Vice-Chair, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts. dFroedtert Memorial Lutheran Hospital Medical College of Wisconsin, Milwaukee, Wisconsin. eStritch School of Medicine Loyola University Chicago, Maywood, Illinois. fMontefiore Medical Center, Bronx, New York. gNorthwestern University Feinberg School of Medicine, Chicago, Illinois; American Academy of Otolaryngology-Head and Neck Surgery. hRush University Medical Center, Chicago, Illinois; Neurosurgery expert. iHouston Methodist Hospital, Houston, Texas. jUniversity of Texas Health Science Center, Houston, Texas. kThe University of Texas MD Anderson Cancer Center, Houston, Texas. lNew York University Langone Medical Center, New York, New York. mMayo Clinic, Rochester, Minnesota. nMetroHealth Medical Center, Cleveland, Ohio. oUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina; American Academy of Neurology. pNorthwestern University Feinberg School of Medicine, Chicago, Illinois; Neurosurgery expert. qGeorge Washington University Hospital, Washington, District of Columbia.


Cranial Neuropathy

Cranial Neuropathy. rUniversity of Iowa Hospital, Iowa City, Iowa, Primary care physician. sUniversity of Colorado Denver, Denver, Colorado. tSpecialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Cranial Neuropathy Special Imaging Considerations MRI is the standard modality for imaging the CNs. Imaging with 3.0T is preferred over 1.5T imaging because of superior signal-to-noise ratios, gradient strength, and spatial resolution, although diagnostic information can be obtained with 1.5T imaging when 3.0T imaging is not available or precluded [5]. A phased-array head coil suffices for most examinations; specialized surface coils may supplement examinations of peripherally located nerves [5,19,20]. Fundamental techniques include thin-cut T1-weighted, T2-weighted, and contrast-enhanced T1-weighted sequences. The unenhanced T1-weighted sequence remains an excellent baseline technique for anatomic evaluation because of the natural contrast provided by fat in the neck and skull base. Diffusion-weighted imaging (DWI) is useful to assess for acute infarctions, cellular tumors, or specific lesions that may affect CN function, such as epidermoids or cholesteatomas. Thin section nonecho planar DWI with decreased susceptibility artifact compared with echo planar DWI allows for increased sensitivity in detection of small cholesteatomas. The use of intravenous (IV) contrast is imperative for the evaluation of cranial neuropathy with MRI. Neck CT also requires the use of IV contrast when evaluating for lesions in the neck causing cranial neuropathy.


Cranial Neuropathy

Cranial Neuropathy. Thin-section imaging with high-spatial resolution is required to directly image the CNs or their course. Slice thickness should be calculated for optimal spatial resolution without introducing partial-volume effect. The primary plane of imaging varies with the CN of interest and should include orthogonal views. The CN nuclei and fascicular nerve segments (brainstem segments) are not well seen on MRI, but their location can be deduced by recognizing surrounding anatomy and are best imaged with various T2-weighted, multi-echo, and fluid-attenuated inversion- recovery (FLAIR) sequences [15]. Three-dimensional isotropic heavily T2-weighted sequences with low CSF artifact provide submillimeter high-spatial and contrast resolution to image the cisternal and dural cave segments of the CNs and can be reformatted into multiple planes [5,21-23]. Intradural and foraminal CN segments, surrounded by a vascular plexus, are best imaged with contrast-enhanced 2- D or 3-D T1-weighted images, contrast-enhanced MR angiography (MRA) or contrast-enhanced modified balanced steady-state free precession (SSFP) sequences in which the nerves appear dark while surrounded by the vascular plexus [5,15,23,24]. The peripheral or extraforaminal segments of the CNs begin as they exit the skull base where they are initially surrounded by fat and are well imaged with high-resolution axial and coronal T1-weighted and T2-weighted sequences and with SSFP sequences as they course within the face and neck [5,15]. Contrast-enhanced fat-suppressed T1-weighted techniques may emphasize abnormal nerves or lesions but can mask subtle pathology if the fat-suppression is nonuniform. Because CN examinations tend to be lengthy, strategies such as parallel imaging may improve patient compliance and image quality [15]. DWI and fiber tract imaging techniques have shown some improvement in visualization of CN fascicles and fiber tracts but are without sufficient reliability for routine clinical use [5,25,26].


Cranial Neuropathy

Cranial Neuropathy. In the setting of cranial neuropathy, thin-cut high-resolution CT can be complementary to MRI in characterizing the osseous integrity of the skull base and skull base foramina. Knowledge of CN anatomy coupled with a careful neurologic examination can aid in tailoring imaging protocols, particularly if a central or peripheral CN palsy can be distinguished clinically. If the probable location of the causative lesion cannot be deduced clinically, imaging of the entire course of the relevant CN may be required because cranial neuropathy can result from pathology affecting the nerve fibers at any point along the course of the nerve and might require multiple imaging modalities. For example, complete evaluation of CN VII includes imaging of the parotid gland and face, because causative lesions can be intraparotid or cutaneous. Head and neck imaging is required to completely image the courses of CN IX, CN XI, and CN XII, which extend into the neck to innervate Cranial Neuropathy end organs. Evaluation of the head, neck, and upper chest is necessary for complete evaluation of the CN X to include the recurrent laryngeal nerve. This can be accomplished by extending the neck scan into the mid thorax (aortic pulmonary window) or by adding a dedicated chest CT. Patients presenting with otalgia may require evaluation of CN V, VII, IX, and X and upper cervical nerves C2 and C3 because any of these nerves may be the source for the otalgia [27]. Most patients with olfactory symptoms do not require imaging, unless history or physical examination warrants it [29]. Causative factors for olfactory impairment can be categorized into three main groups, including conduction loss from sinonasal passage obstruction, sensorineural loss from olfactory neuroepithelial damage, and dysfunction from central nervous system disorders [30,31]. Trauma, aging, upper respiratory infections, and inflammatory sinonasal disorders most commonly affect the sense of smell [30-32].


Cranial Neuropathy

Cranial Neuropathy. Tumors affecting the cribriform plate such as squamous cell carcinomas, meningiomas, and esthesioneuroblastoma or olfactory neuroblastomas; inflammatory lesions such as sarcoidosis and granulomatosis with polyangiitis; and congenital conditions such as cephaloceles and Kallmann syndrome can also result in impaired olfaction [32-34]. Olfactory dysfunction is also associated with neurodegenerative, cognitive, and mood disorders including Alzheimer disease, Parkinson disease, and depression [30,35-38]. CT Head There is no relevant literature to support the use of CT head in the evaluation of the olfactory nerve. CT Maxillofacial CT of the paranasal sinuses and face is useful to evaluate fractures, paranasal sinus inflammatory disease, and bony anatomy that impact olfaction [29,39-41]. CT can be used to characterize sinonasal inflammatory disease. Rhinosinusitis with nasal polyposis severity, as characterized by CT, correlates with worse olfaction [31]. Although the anatomic subunits of the olfactory pathway except for the olfactory bulbs cannot be directly visualized by CT, imaging protocols should cover the major anatomic divisions of the olfactory nerve and pathway, including the olfactory epithelium, which is located in the upper nasal cavity; the olfactory neurons and bulbs, located in the cribriform plate and inferior frontal lobes; and the olfactory pathways, which travel in portions of the temporal and Cranial Neuropathy frontal lobes [4]. No IV contrast is necessary for osseous evaluation including posttrauma and for uncomplicated inflammatory sinonasal disease. Contrast-enhanced CT is useful to evaluate granulomatous and neoplastic disease. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CTA Head There is no relevant literature to support the use of CT angiography (CTA) head in the evaluation of the olfactory nerve.


Cranial Neuropathy

Cranial Neuropathy. FDG-PET/CT Efforts using functional MRI, single-photon emission CT, and fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET in studying olfactory dysfunction and the role of olfaction in neurodegenerative disorders remain largely investigative and are not generally used in routine evaluations [42-48]. MRA Head There is no relevant literature to support the use of MRA head in the evaluation of the olfactory nerve. MRI Head MRI is the mainstay for directly imaging the olfactory apparatus and is best assessed with MRI orbits, face, and neck MRI rather than MRI head, allowing for assessment of the sinonasal components of the olfactory apparatus while simultaneously evaluating the relevant brain structures that can affect olfaction. US Neck There is no relevant literature to support the use of ultrasound (US) neck in the evaluation of the olfactory nerve. Variant 2: Unilateral isolated weakness of the mastication muscles, paralysis of the mastication muscles, sensory abnormalities of the face and head, facial numbness, or trigeminal neuralgia (trigeminal nerve, CN V). Initial imaging. The trigeminal nerve (CN V) is the largest CN, providing general sensation to the face, part of the scalp, the nasal cavity, oral cavity, and teeth. It also provides branchial motor innervation to the muscles of mastication. The 4 central trigeminal nerve nuclei are located within the brainstem and include the mesencephalic nucleus, the principal sensory nucleus, the motor nucleus, and the spinal trigeminal tract and nucleus. The spinal trigeminal tract and nucleus extend from the midpons caudally into the upper cervical cord at the C2-C4 levels. The trigeminal nerve is divided into 3 main divisions, known as the ophthalmic (V1), maxillary (V2), and mandibular (V3) branches [3]. Symptoms of trigeminal neuropathy or neuropathic pain syndromes vary with the involved segment and division and may or may not include other sensory deficits (such as facial numbness) or motor deficits (such as weakness with mastication).


Cranial Neuropathy

Cranial Neuropathy. In patients with clinical features of trigeminal neuropathy, initial imaging is performed along the entire course of the trigeminal nerve to evaluate for a causative lesion [57]. The trigeminal nerve can be affected by processes anywhere along its course from the brainstem to its peripheral branches; consequently, imaging should cover the entire course of the nerve. Brainstem lesions can affect the trigeminal nerve but rarely lead to isolated trigeminal neuropathy because of the close proximity of neural structures within the brainstem. In particular, multiple sclerosis can result in trigeminal neuralgia, necessitating imaging of the brainstem to look for demyelinating disease [58-61]. Other brainstem lesions that can affect the trigeminal nerve include infarction, hemorrhage, vascular lesions (such as compressing vascular loops, aneurysms, and Cranial Neuropathy vertebrobasilar dolichoectasia), inflammatory and infectious conditions (such as meningitis, encephalitis, sarcoidosis, and demyelinating disease), and tumors (such as gliomas, lymphomas, and metastases) [59]. Tumors, vascular lesions, and inflammatory processes may also affect the cisternal, dural cave, cavernous, foraminal, and extracranial branches of the nerve as they traverse the Meckel cave, the pterygopalatine fossa, the orbit, the skull base, and the masticator space [59,62,63]. Perineural spread of tumor, discussed in Variant 10, can affect the trigeminal nerve anywhere along its course. CT Head CT is a complementary study for evaluating the osseous integrity of the skull base and neural foramina. However, standard coverage with a CT Head is insufficient to evaluate the full extent of the trigeminal nerve divisions in the face. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CT Maxillofacial Maxillofacial CT is a complementary study for evaluating the osseous integrity of the skull base and neural foramina, which can be accomplished without IV contrast.


Cranial Neuropathy

Cranial Neuropathy. CT may be helpful for visualizing perineural fat planes, which can be distorted or obliterated in patients with lesions affecting the trigeminal nerve, although MRI offers improved detection of perineural tumor spread (discussed in Variant 10) compared with CT, which has a sensitivity and specificity of 88% and 89%, respectively [64-66]. CT with IV contrast offers the benefits of vascular and mucosal enhancement and may highlight enhancing lesions. There is no relevant literature to support the use of combined pre- and postcontrast imaging. Thin section contrast-enhanced navigation protocol CT is useful for noninvasive treatment planning in patients with known trigeminal neuralgia [67]. CTA Head There is no relevant literature to support the use of CTA head in the initial evaluation of trigeminal neuropathy. In patients with clinical features of trigeminal neuralgia, high-resolution combined MRI, MRA, and CTA may be used to assess for vascular loops compressing the fifth nerve. Anatomic and dedicated vascular imaging play a complementary role. Structural MRI evaluation of the nerve and its relationship to vasculature is more commonly reported in the literature, likely related to the improved soft tissue contrast of MRI compared with CT [23,68-76]. CTA has been used to characterize the relationship of arterial vasculature relative to the fifth nerve in patients with a clinical diagnosis of trigeminal neuralgia but is less commonly used than MRI and MRA because it does not provide simultaneous high-resolution imaging of the trigeminal nerve provided by MRI [77]. MRA Head There is no relevant literature to support the use of MRA head in the initial evaluation of trigeminal neuropathy.


Cranial Neuropathy

Cranial Neuropathy. In patients with clinical features of trigeminal neuralgia, MRA is commonly used as a complementary study to high- resolution MRI in assessing for vascular compression of the CN V with sensitivities of combined MRI with MRA ranging from 97% to 100%, specificities reported as 100%, and good to strong agreement found compared with surgical findings [69,71-73,76]. One group reported a lower sensitivity (50% at 3T and 33% at 1.5T) of combined high-resolution MRI with MRA for detection of neurovascular compression of CN V by smaller vessels such as the anterior inferior cerebellar artery [71]. Cranial Neuropathy In patients with clinical features of trigeminal neuralgia, 3-D heavily T2-weighted MRI sequences, MRA, and a combination of these techniques are commonly used noninvasive methods for characterizing the anatomy of vascular loops potentially compressing the fifth nerve and correlate well with surgical findings [23,68-76]. Congruence rates of imaging and intraoperative findings for neurovascular contact range from 83% to 100% [68- 70,72,75,78]. Both false-positive and false-negative imaging studies occur when assessing for neurovascular contact in the setting of trigeminal neuralgia; consequently, MRI is supportive rather than diagnostic in selecting candidates for microvascular decompression and should be interpreted in the context of the site of symptoms [69,73-75,78]. Imaging evidence of vascular trigeminal nerve root compression, the degree of compression, location of contact, and nerve volume may have prognostic value [73,77,79-81]. Trigeminal nerve size measurements have been reported as smaller on the symptomatic side in trigeminal neuralgia as measured from thin-cut MRI [82-84]. Preoperative imaging is useful for surgical planning [85]. Advanced MRI techniques including diffusion tensor imaging (DTI), functional MRI, and voxel-based morphometry are being used to research the pathophysiology of trigeminal neuralgia.


Cranial Neuropathy

Cranial Neuropathy. DTI metrics suggest microstructural tissue changes in symptomatic nerves in the setting of trigeminal neuralgia compared with asymptomatic nerves and may be useful for making treatment decisions [68,86-93]. Advanced MRI techniques have also detected structural alterations in gray matter and white matter in patients with trigeminal neuralgia [94-97]. MR neurography is an emerging technique that may be useful in characterizing the etiology of peripheral trigeminal neuropathy [98]. In patients with clinical features of trigeminal neuralgia, 3-D heavily T2-weighted MRI sequences, MRA, and a combination of these techniques are commonly used noninvasive methods for characterizing the anatomy of vascular loops potentially compressing the cisternal segment of the fifth nerve and correlate well with surgical findings [23,68-76]. Congruence rates of imaging and intraoperative findings for neurovascular contact range from 83% to 100% [68-70,72,75,78]. Both false-positive and false-negative imaging studies occur when assessing for neurovascular contact in the setting of trigeminal neuralgia; consequently, MRI is supportive rather than diagnostic in selecting candidates for microvascular decompression and should be interpreted in the context of the site of symptoms [69,73-75,78]. Imaging evidence of vascular trigeminal nerve root compression, the degree of compression, location of contact, and nerve volume may have prognostic value [73,77,79-81]. Trigeminal nerve size measurements have been reported as smaller on the symptomatic side in trigeminal neuralgia as measured from thin-cut MRI [82-84]. Preoperative imaging is useful for surgical planning [85]. Advanced MRI techniques including DTI, functional MRI, and voxel-based morphometry are being used to research the pathophysiology of trigeminal neuralgia.


Cranial Neuropathy

Cranial Neuropathy. DTI metrics suggest microstructural tissue changes in symptomatic nerves in the setting of trigeminal neuralgia compared with asymptomatic nerves and may be useful for making treatment decisions [68,86-93]. Advanced MRI techniques have also detected structural alterations in gray matter and white matter in patients with trigeminal neuralgia [94-97]. MR neurography is an emerging technique that may be useful in characterizing the etiology of peripheral trigeminal neuropathy [98]. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT skull base to mid-thigh in the evaluation of isolated trigeminal mononeuropathy or isolated unilateral trigeminal neuralgia. US Neck There is no relevant literature to support the use of US neck in the evaluation of isolated trigeminal mononeuropathy or isolated unilateral trigeminal neuralgia. Cranial Neuropathy Variant 3: Unilateral isolated weakness of the facial expression, paralysis of the facial expression, hemifacial spasm, or Bell palsy (facial nerve, CN VII). Initial imaging. The facial nerve (CN VII) is one of the most complex CNs and contains branchial motor (innervation to the muscles of facial expression), visceral motor (parasympathetic innervation to most of the glands of the head), general sensory (surface innervations to a small portion of the external ear and tympanic membrane), and special sensory (taste to the anterior two-thirds of the tongue) functions [2,99]. From its nucleus in the pons, the intraparenchymal fascicular or attached segment courses superiorly along the surface of the pons after which it turns anteriorly exiting the brainstem at the pontomedullary sulcus, which is referred to as the root exit point. Its parenchymal fascicular or attached segment courses superiorly along the surface of the pons after which it turns anteriorly, detaching from the pons at the root detachment point [5,100,101].


Cranial Neuropathy

Cranial Neuropathy. It then traverses the cerebellopontine angle in its cisternal segment, enters the internal auditory canal within its meatal segment, and courses through the temporal bone (which includes the labyrinthine, tympanic, mastoid segments, and geniculate ganglion). The facial nerve exits the temporal bone at the stylomastoid foramen, and the extracranial segment courses through the parotid gland. Peripheral, nuclear, or infranuclear facial nerve paralysis presents as ipsilateral facial paralysis with involvement of the forehead (which is usually spared with a supranuclear facial nerve palsy) and can result from pathology affecting the facial nerve nucleus or any portion of the facial nerve after exiting the brainstem within its intracranial and extracranial segments. Within the pons, the facial nuclei can be affected by intra-axial conditions such as infarction, vascular malformations, tumors, and multiple sclerosis. Brainstem lesions are often accompanied by additional neurologic symptoms that can help localize the lesion clinically [102,103]. Rarely brainstem or cortical infarct can result in an isolated facial nerve palsy [102,103]. As the facial nerve exits the brainstem and courses within the cerebellopontine angle, the internal auditory canal, and through the temporal bone, it may be affected by facial and vestibular schwannomas, meningiomas, vascular lesions, inflammation, cholesteatomas, paragangliomas, epidermoid cysts, trauma, and intrinsic bone tumors. The extracranial facial nerve may be affected by inflammation, parotid tumors, conditions of the neighboring anatomic spaces, and skull base pathology including carcinomas, sarcomas, trauma, and inflammatory disease [99,102]. Perineural spread of a tumor can result in facial nerve palsy and is discussed in Variant 10 [104]. Facial nerve palsy can present with facial droop, pain around the jaw or ear, hyperacusis, tinnitus, reduced taste, and decreased lacrimation or salivation.


Cranial Neuropathy

Cranial Neuropathy. Facial paralysis in the form of Bell palsy is the most common cause of acute peripheral facial nerve palsy, attributed to inflammation of the facial nerve, which may be idiopathic or due to herpes simplex virus. Most patients experience complete recovery of function by 6 months, which can be hastened with steroids [102]. In general, Bell palsy patients need not be imaged unless the symptoms are atypical, recurrent, or persist for 2 to 4 months [102]. Unilateral hyperactivity of the facial nerve can occur, resulting in the spasm of the facial musculature referred to as hemifacial spasm. Hemifacial spasm is most commonly the result of vascular compression of the facial nerve, usually within the centrally (oligodendrocyte) myelinated portion of the nerve [100]. CT Head There is no relevant literature to support the use of routine CT head alone in the evaluation of unilateral isolated facial nerve palsy. CT Temporal Bone High-resolution thin-cut temporal bone CT provides complementary useful information to MRI by characterizing the osseous integrity of the temporal bone through which the facial nerve courses. CT imaging excels at osseous imaging and characterizes well temporal bone fractures, presurgical osseous anatomy, bony facial nerve canal involvement with inflammatory middle ear disease, facial canal foraminal expansion, patterns of bone erosion, and intrinsic bone tumor matrices [2,99,105-108]. High-resolution temporal bone CT with thin sections should be obtained to evaluate the course of CN VII. Contrast may be useful in the setting of infection or when a tumor is suspected. There is no relevant literature to support the use of combined pre- and postcontrast imaging. High-resolution noncontrast CT of the temporal bone is useful to characterize temporal bone fractures including fractures through the facial nerve canal, but sensitivity for nondisplaced fracture has been shown to vary with fracture location and is lowest in the mastoid segment [105,108]. Cranial Neuropathy


Cranial Neuropathy

Cranial Neuropathy. CT Maxillofacial Temporal bone CT (complementary to MRI in patients with facial nerve palsy) is the preferred CT study and typically provides better spatial resolution than maxillofacial CT when assessing the fine detailed anatomy of the temporal bone and bony facial nerve canal. Maxillofacial CT provides better spatial resolution than head CT and, depending on institutional protocols, may provide sufficient spatial resolution to be complementary to MRI to characterize the osseous integrity of the temporal bone and assess the extracranial course of the facial nerve although the nerve itself is not directly imaged with CT [2,99,105-108]. Contrast may be useful when infection or a tumor is suspected. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CTA Head There is no relevant literature to support the use of CTA head as an isolated study in the initial evaluation of acute unilateral facial nerve palsy. Rarely brainstem or cortical infarct can result in isolated facial nerve palsy, and if clinically suspected, CTA may be complementary to MRI in this clinical scenario [102,103] to characterize the vasculature. CTA is uncommonly reported as a complementary study to thin-cut high-resolution MRI for characterizing the anatomy of vascular loops potentially compressing the centrally myelinated portion of the facial nerve [109]. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT skull base to mid-thigh in the evaluation of isolated unilateral facial nerve palsy or hemifacial spasm. MRA Head There is no relevant literature to support the use of MRA alone in the initial evaluation of acute unilateral facial nerve palsy. Rarely brainstem or cortical infarct can result in isolated facial nerve palsy, and if clinically suspected, MRA may be complementary to MRI in this clinical scenario [102,103] to characterize the vasculature. MRA may be useful in the assessment of hemifacial spasm.


Cranial Neuropathy

Cranial Neuropathy. In patients with clinical features of hemifacial spasm, MRA can be complementary to 3-D heavily T2-weighted MRI sequences for characterizing the anatomy of vascular loops potentially compressing the centrally myelinated portion of the facial nerve with sensitivity and accuracy reported as >95% and a good correlation with surgical findings [76,109,110]. Volumetric and 3T imaging have been reported to provide improved visualization of the facial nerve and its surrounding perineural vascular plexus [7,19,111,113]. In general, Bell palsy patients need not be imaged unless the symptoms are atypical, recurrent, or persist for 2 to 4 months [102]. When imaging is considered, MRI is the method of choice. Variable abnormal enhancement patterns may be seen in the canalicular, labyrinthine, geniculate, tympanic, and mastoid portions of the nerve [106,117-122]. There is a lack of consensus regarding the prognostic value of MRI in Bell palsy [118-121], and MRI is most useful for excluding other causes of facial nerve palsy. High-resolution thin-cut contrast-enhanced MRI is an especially useful method to evaluate for perineural spread of a tumor, which can affect CN VII and is discussed in Variant 10. Sensitivities for MRI detection of perineural spread of a tumor range from 73% to 100% and vary according to the nerve evaluated and timing of imaging relative to tissue sampling [65,104,123-125]. In patients with clinical features of hemifacial spasm, 3-D heavily T2-weighted MRI sequences and MRA are noninvasive methods for characterizing the anatomy of vascular loops potentially compressing the centrally myelinated portion of the facial nerve and correlate well with surgical findings [76,78,100,101,110]. Both false- positive and false-negative imaging studies occur when assessing for neurovascular contact in the setting of hemifacial spasm; consequently MRI is supportive rather than diagnostic in selecting candidates for microvascular Cranial Neuropathy decompression [78,100].


Cranial Neuropathy

Cranial Neuropathy. In patients with failed initial microvascular decompression surgery, heavily T2-weighted MRI may be helpful to delineate the cause [101]. DTI is an advanced imaging technique that may be useful in assessing the facial nerve. Several studies suggest that DTI is accurate for the preoperative localization of the cisternal facial nerve to avoid iatrogenic injury in patients with cerebellopontine angle tumors [107,126-128]. Research indicates that DTI may have future use localizing the intraparotid facial nerve and detecting perineural spread of a tumor [129,130]. Volumetric and 3T imaging have been reported to provide improved visualization of the facial nerve and its surrounding perineural vascular plexus [7,19,111,113]. In general, Bell palsy patients do not need to be imaged unless the symptoms are atypical, recurrent, or persistent for 2 to 4 months [102]. When imaging is considered, MRI is the method of choice. Variable abnormal enhancement patterns may be seen in the canalicular, labyrinthine, geniculate, tympanic, and mastoid portions of the nerve [106,117-122]. There is a lack of consensus regarding the prognostic value of MRI in Bell palsy [118-121], and MRI is most useful for excluding other causes of facial nerve palsy. High-resolution thin-cut contrast-enhanced MRI is an especially useful method to evaluate for perineural spread of a tumor, which can affect CN VII and is discussed in Variant 10. Sensitivities for MRI detection of perineural spread of a tumor range from 73% to 100% and vary according to the nerve evaluated and timing of imaging relative to tissue sampling [65,104,123-125]. In patients with clinical features of hemifacial spasm, 3-D heavily T2-weighted MRI sequences and MRA are noninvasive methods for characterizing the anatomy of vascular loops potentially compressing the centrally myelinated portion of the facial nerve and correlate well with surgical findings [76,78,100,101,110].


Cranial Neuropathy

Cranial Neuropathy. Both false- positive and false-negative imaging studies occur when assessing for neurovascular contact in the setting of hemifacial spasm; consequently MRI is supportive rather than diagnostic in selecting candidates for microvascular decompression [78,100]. In patients with failed initial microvascular decompression surgery, heavily T2-weighted MRI may be helpful to delineate the cause [101]. DTI is an advanced imaging technique that may be useful in assessing the facial nerve. Several studies suggest that DTI is accurate for the preoperative localization of the cisternal facial nerve to avoid iatrogenic injury in patients with cerebellopontine angle tumors [107,126-128]. Research indicates that DTI may have future use localizing the intraparotid facial nerve and detecting perineural spread of tumor [129,130]. US Neck There is no relevant literature to support the use of US neck in the evaluation of isolated unilateral facial nerve palsy or hemifacial spasm. Variant 4: Multiple different middle cranial nerve palsies (CN V-VII). Initial imaging. Multiple CN nuclei are closely approximated within the brainstem, from which motor fibers originate and sensory fibers terminate. A small single brainstem lesion can produce severe and mixed neurologic deficits, including multiple cranial neuropathies, often times with some component of cerebellar, motor, or somatosensory deficit helping in clinically localizing the lesion. The pons connects the midbrain to the medulla. The dorsal pontine tegmentum contains white matter tracts and CN V through CN VIII nuclei, and the ventral pons contains corticospinal, corticobulbar, and corticopontine tracts [1,131]. After exiting the pons, the first and second divisions of the trigeminal nerve course along the lateral wall of the cavernous sinus, the abducens nerve courses through the cavernous sinus, and CNs VII and VIII extend through the cerebellopontine angle toward the porus acusticus. The third division of the trigeminal exits the skull base via foramen ovale.


Cranial Neuropathy

Cranial Neuropathy. Pontine lesions can affect CNs V, VI, VII, and/or VIII. Ischemic and hemorrhagic infarcts are the most frequent cause of acute brainstem syndromes with the pons most frequently affected [1,132]. Nonischemic lesions affecting Cranial Neuropathy the brainstem include trauma, demyelinating disease, encephalitis, neoplasms, central pontine myelinolysis, neurodegenerative disorders, and syringobulbia [18,131,132]. Pontine syndromes causing variable involvement of CNs V-VIII, along with other neurologic deficits, include Millard-Gubler syndrome, Foville syndrome, locked-in syndrome, and facial colliculus syndrome [131]. The internal carotid artery with its surrounding sympathetic plexus and the abducens nerve extend through the center of the cavernous sinus, and the oculomotor, trochlear, and trigeminal nerves (1st and 2nd division) extend along the lateral wall of the cavernous sinus. Cavernous sinus lesions can result in isolated or multiple cranial neuropathies including involvement of the abducens and trigeminal nerves. Tumors, vascular lesions, infection, and inflammatory disorders can lead to cavernous sinus syndrome [18]. The cerebellopontine angle spans a craniocaudal extent that encompasses the cisternal portions of CNs V-X and is most frequently affected by benign tumors. Sensorineural hearing loss and tinnitus are the most common symptoms but can be accompanied by neuropathies of CNs V, VI, VII, IX, and X with larger tumors [18]. The combination of ipsilateral CN V and CN VII palsies raises concern for perineural spread of tumor, which is discussed in Variant 10. Additionally, leptomeningeal processes can lead to variable patterns of cranial neuropathy [18,132]. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the initial evaluation of multiple middle CN palsies.


Cranial Neuropathy

Cranial Neuropathy. Depending on institutional protocols used for high-resolution skull base imaging, maxillofacial CT may be complementary to an MRI exam if a skull base lesion is found to be the cause of multiple middle CN palsies and can be useful to characterize the osseous integrity of the skull base, intratumoral calcification, and skull base foramina [134]. Contrast should be administered. Noncontrast CT may also be an alternate option when used as complementary to the MRI. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the initial evaluation of multiple middle CN palsies. Depending on institutional protocols used for high-resolution skull base imaging, temporal bone CT may be complementary to contrast-enhanced MRI if a skull base lesion is found to be the cause of multiple middle CN palsies and can be useful to characterize the osseous integrity of the base, intratumoral calcification, and skull base foramina [134]. Contrast should be administered. Noncontrast CT may also be an alternate option when used as complementary to the MRI. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CT Neck There is no relevant literature to support routine use of neck CT in the initial evaluation of multiple middle cranial palsies. If perineural tumor spread (discussed in Variant 10) is suspected based on clinical features, most notably involving both CNs V and VII, neck CT is complementary to MRI for characterizing osseous changes of skull base neural foramina and may be useful to characterize perineural fat and stage the neck [64,66]. Contrast should be administered if possible. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CTA Head There is no relevant literature to support routine use of CTA head in the initial evaluation of multiple middle cranial palsies.


Cranial Neuropathy

Cranial Neuropathy. Ischemic and hemorrhagic infarcts are the most frequent cause of acute brainstem syndromes, which can result in multiple middle CN palsies [131,132,135]. CTA may be complementary to brain MRI or head CT to characterize the vasculature in these clinical scenarios. Cranial Neuropathy FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use FDG-PET/CT skull base to mid-thigh in the initial evaluation of multiple middle cranial palsies. MRA Head There is no relevant literature to support routine use of MRA head in the initial evaluation of multiple middle cranial palsies. Ischemic and hemorrhagic infarcts are the most frequent cause of acute brainstem syndromes, which can result in multiple middle CN palsies [131,132,135]. MRA may be complementary to MRI brain to characterize the vasculature in these clinical scenarios. DWI can be used to assess for acute brainstem infarction, cholesteatoma, and for characterizing tumor cellularity. False-negative DWI can occur in the setting of very small ischemic brainstem infarcts [137,138]. Thin-section coronal DWI or thinner axial DWI may improve sensitivity for detecting acute brainstem infarction, with nearly 25% of acute brainstem infarcts more easily seen on thin-cut coronal DWI compared with standard axial DWI in one study [138]. The combination of ipsilateral CN V and CN VII palsies raises concern for perineural spread of a tumor, which is discussed in Variant 10. DWI can be used to assess for acute brainstem infarction, cholesteatoma, and for characterizing tumor cellularity. False-negative DWI can occur in the setting of very small ischemic brainstem infarcts [137,138]. Thin-section coronal DWI or thinner axial DWI may improve sensitivity for detecting acute brainstem infarction, with nearly 25% of acute brainstem infarcts more easily seen on thin-cut coronal DWI compared with standard axial DWI in one study [138].


Cranial Neuropathy

Cranial Neuropathy. The combination of ipsilateral CN V and CN VII palsies raises concern for perineural spread of a tumor, which is discussed in Variant 10. US Neck There is no relevant literature to support the use of US neck in the initial evaluation of multiple middle cranial palsies. Variant 5: Oropharyngeal neurogenic dysphagia or oropharyngeal pain (glossopharyngeal nerve, CN IX). Initial imaging. The glossopharyngeal nerve (CN IX) arises in the medulla and is responsible for branchial motor innervation to the stylopharyngeus muscle, which elevates the palate, and visceral motor parasympathetic innervation to the parotid gland [2]. Visceral sensory innervation to the carotid sinus plays a role in regulating circulation and general and special sensory innervation supply sensation and taste to the posterior tongue. The nerve exits the jugular foramen in close proximity to the vagus (CN X) and the spinal accessory (CN XI) nerves [2,24]. Noniatrogenic isolated syndromes involving the glossopharyngeal nerve are very rare. Nerve root section or nerve ablation results in Cranial Neuropathy variable degrees of dysphagia and ipsilateral sensory loss on the pharynx and posterior tongue [139]. Intra- parenchymal lesions can affect CN IX, including gliomas, lymphomas, metastases, vascular malformations, infarctions, demyelinating lesions, and inflammatory abnormalities. Leptomeningeal metastases, granulomatous disease, and even tortuosity or aneurysmal dilatation of vessels may affect the nerve as it enters the subarachnoid cistern. Lesions in the region of the posterior skull base and jugular foramen, such as metastases, schwannomas, paragangliomas, and meningiomas, usually also involve the other lower CNs [140,141]. Tonsillar pain syndromes and loss of a gag reflex accompanied by impaired taste and sensation along the posterior one-third of the tongue and palate may signal a glossopharyngeal nerve lesion [2,141].


Cranial Neuropathy

Cranial Neuropathy. Glossopharyngeal neuralgia presents as severe pain in the oropharyngeal and otic regions, classically triggered by swallowing, and is typically caused by neurovascular compression, although a minority of cases may be caused by trauma, an elongated calcified stylohyoid ligament, and neoplasms along the course of the nerve, including in the neck [142,143]. CT Head There is no relevant literature to support the use of routine noncontrast head CT in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. CT Neck Neck CT is complementary to MRI orbits, face, and neck in assessing patients with isolated CN IX palsy. Neck CT can delineate skull base erosion, identify deep space neck masses, intratumoral calcification, and the bony margins of the jugular foramen and nearby skull base foramina as well as image the extracranial course of the CN IX and its innervated structures in the pharynx and carotid space [144-148]. It does not image the intracranial course of CN IX or the brainstem well, which are best assessed with MRI. Imaging protocols should include thin-cut high- resolution bone windows through the posterior skull base. Contrast is strongly preferred for soft tissue characterization. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CT neck is also useful to characterize the anatomy of the stylohyoid ligament in patients with glossopharyngeal pain [142]. In cases of glossopharyngeal neuralgia, imaging should include the pharynx and larynx to exclude a mucosal neoplasm as an etiology.


Cranial Neuropathy

Cranial Neuropathy. CTA Head and Neck There is no relevant literature to support the use of CTA in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT skull base to mid-thigh in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. MRA Head and Neck There is no relevant literature to support routine use of MRA head and neck to assess vasculature in the initial evaluation of glossopharyngeal palsy, although MRA focused on the posterior skull base can be complementary to thin-cut high-resolution skull base technique, contrast-enhanced MRI orbits, face, and neck, or MRI head in patients with glossopharyngeal nerve palsy. Contrast-enhanced MRA focused on the posterior skull provides detailed imaging of the lower CNs within the jugular foramen and their relationship to the hypoglossal nerve as they exit the skull base, with CN IX reportedly well imaged in 100% of cases using contrast-enhanced high-resolution MRA [24,149]. MRA can be complementary to thin-cut high-resolution MRI sequences to assess for neurovascular compression in patients with glossopharyngeal neuralgia and has demonstrated agreement with surgically confirmed neurovascular compression in all patients in 2 small studies [143,149,150]. Cranial Neuropathy Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the nerves within the jugular foramen and their relationship to the hypoglossal nerve as they exit the skull base, visualizing CN IX in 90% to 100% of imaged patients [24]. Various combinations of high-resolution 3-D T2-weighted imaging, MRA, and 3-D T1-weighted contrast-enhanced sequences can be used to assess for neurovascular compression [143,149-151] and have demonstrated agreement with surgical findings in all patients in two small studies [143,150].


Cranial Neuropathy

Cranial Neuropathy. Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the nerves within the jugular foramen and their relationship to the hypoglossal nerve as they exit the skull base, visualizing CN IX in 90% to 100% of imaged patients [24]. Various combinations of high-resolution 3-D T2-weighted imaging, MRA, and 3-D T1-weighted contrast-enhanced sequences can be used to assess for neurovascular compression [143,149-151] and have demonstrated agreement with surgical findings in all patients in two small studies [143,150]. US Neck There is no relevant literature to support the use of US neck in the initial evaluation of oropharyngeal neurogenic dysphagia or oropharyngeal pain. Variant 6: Unilateral isolated palatal or vocal cord paralysis or both (vagal nerve, CN X). Initial imaging. The vagus nerve (CN X) supplies visceral sensation to the pharynx, larynx, and viscera and general sensation to the ear. Branchial motor branches innervate muscles of the pharynx via the pharyngeal branches and the larynx via the superior and recurrent laryngeal nerves, and visceral motor branches play a predominant role in parasympathetic supply to the thorax and abdomen [2]. The vagus nerve runs the longest course in the body of any CN and is therefore vulnerable to a wide range of pathologies occurring throughout its trajectory from the posterior fossa and skull base to the neck, thorax, and abdomen. Within the neck it descends in the posterior carotid sheath. At the base of the neck, the recurrent laryngeal branch of the right vagus nerve turns upward and medial posterior to the subclavian artery, ascending in the tracheoesophageal groove. The left recurrent laryngeal nerve arises to the left of the aortic arch, turns upward in the aortopulmonary window beneath the ligamentum arteriosum, ascending in the left tracheoesophageal groove.


Cranial Neuropathy

Cranial Neuropathy. The recurrent laryngeal nerves innervate all the laryngeal muscles, with the exception of the cricothyroid. Isolated vagal palsy can be central or peripheral, due to complete vagal nerve dysfunction or isolated impairment of the recurrent laryngeal nerve, respectively. Lesions proximal to the pharyngeal branches cause ipsilateral palatal weakness. Because lesions anywhere along the course of the vagus nerve may potentially cause vocal cord paralysis, Cranial Neuropathy the imaging protocol must visualize the full extent of the nerve from the skull base to the mid chest in this situation [2,152]. In the case of a central palsy, careful neurologic examination and patient history may help to locate the lesion to the central nervous system. Intramedullary lesions that can affect the vagus nucleus include demyelination, infarction, neoplasms, motor neuron disorders, and syringobulbia. Intracranial processes such as meningiomas, schwannomas, metastases, granulomatous disease, and infection may affect the nerve as it exits the medulla. Paragangliomas, schwannomas, meningiomas, and metastases involving the skull base may affect the vagus nerve and the neighboring glossopharyngeal nerve (CN IX) or accessory nerve (CN XI) by infiltration of fibers or by compression [2,152,153]. Direct and indirect signs of vocal cord paralysis can be seen on CT [152]. Optimal evidence-based imaging algorithms in the setting of unilateral vocal cord paralysis without an apparent cause are not established. One of the most troubling symptoms of vagus dysfunction is vocal cord paralysis. Injury of the recurrent laryngeal branch in the neck or upper thorax can be idiopathic, due to iatrogenic injury from surgery or intubation, trauma, infection, inflammation, vascular lesions, and neoplasms arising in the neck and thorax. Moreover, thoracic causes of vocal cord paralysis, such as lung cancer, tuberculosis, and thoracic aortic aneurysm, are common [154-157].


Cranial Neuropathy

Cranial Neuropathy. CT Chest Evaluation of the posterior fossa, neck, and upper chest is necessary for complete evaluation of the CN X, including the recurrent laryngeal nerve. Below the skull base, the vagus nerve is not directly imaged, although its course from the skull base to the carina can be imaged with contrast-enhanced neck CT extended through the aortopulmonary window. CT chest alone does cover the entire course of the vagus nerve, but it can be combined simultaneously and sequentially with CT neck to image the intrathoracic course of the vagus nerve. Preferably contrast should be administered. There is no relevant literature to support the use of combined pre- and postcontrast imaging. Although chest radiographs may detect large thoracic causes of vocal cord paralysis, chest CT is more sensitive, particularly for detecting aortopulmonary window and paratracheal lesions [158]. CT Head There is no relevant literature to support the use of routine CT head alone in the evaluation of unilateral isolated vagal nerve palsy. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the evaluation of isolated CN X palsy. Contrast-enhanced neck CT extended through the aortopulmonary window is useful for initial evaluation of isolated CN X palsy and allows imaging of the osseous integrity of the skull base and assessment of the full extent of the recurrent laryngeal nerve. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the evaluation of isolated CN X palsy. CT Neck Evaluation of the posterior fossa, neck, and upper chest is necessary for complete evaluation of the CN X, including the recurrent laryngeal nerve, and can be achieved well with contrast-enhanced neck CT extended through the AP window. Below the skull base, the vagus nerve is not directly visualized, although its course from the skull base to the carina can be imaged with neck CT.


Cranial Neuropathy

Cranial Neuropathy. With its rapid scanning time, high-spatial resolution, and multiplanar capability, contrast-enhanced neck CT conveniently allows imaging of the jugular foramen, the full extracranial course of the vagus nerve, direct imaging of the larynx, and assessment of the full extent of the recurrent laryngeal nerve when extended through the aortopulmonary window. Imaging protocols should include thin-cut high- resolution bone windows through the posterior skull base. Contrast should be administered. Noncontrast neck CT offers limited evaluation of the neck and may be an alternate option for this clinical scenario. There is no relevant literature to support the use of combined pre- and postcontrast imaging. Direct and indirect signs of vocal cord paralysis can be seen on CT [152]. CT may differentiate traumatic arytenoid dislocation from neurogenic paralysis [153]. Optimal evidence-based imaging algorithms in the setting of unilateral vocal cord paralysis without an apparent cause are not established. Several studies support the use of CT for detecting a cause for unilateral vocal cord paralysis with diagnostic yields ranging from 23.5% to 47.5% [155,157]. One study found CT had a higher diagnostic yield of 40% among patients >65 years of age [131]. In patients with a diagnosis of idiopathic vocal cord Cranial Neuropathy paralysis, repeat CT may be helpful to detect occult causes of paralysis [156]. Other studies report low diagnostic yields ranging from 0% to 6% [159-161]. Noninvasive virtual laryngoscopy using ultrahigh-resolution CT and cine MRI allowing the patient to perform phonation and breathing maneuvers during imaging are emerging technologies [162,163]. CTA Head and Neck There is no relevant literature to support the use of CTA in the evaluation of unilateral isolated vagal nerve palsy. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is not routinely used in the initial evaluation of vocal cord paralysis or vagus nerve palsy.


Cranial Neuropathy

Cranial Neuropathy. FDG- PET/CT may be useful after initial cross-sectional imaging in patients with a known primary malignancy for both staging and therapy assessment [164]. It may yield false-positive findings if not interpreted carefully in the clinical context in patients with vocal cord palsy or following vocal fold augmentation [152,165-167]. MRA Head and Neck There is no relevant literature to support the use of MRA in the evaluation of vasculature in unilateral isolated vagal nerve palsy. Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves within the jugular foramen, including CN X, which is well visualized in 94% to 100% of imaged patients [24]. Below the skull base, the vagus nerve is not directly imaged by CT and MRI, though its course from the skull base to the carina can be imaged by either modality. Contrast-enhanced CT is typically accessible and conveniently allows complete and rapid imaging of the full extracranial course of the vagus nerve and direct imaging of the larynx and can be extended into the upper thorax to cover the entire course of the left recurrent laryngeal nerve. Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves within the jugular foramen, including CN X, which is well visualized in 94% to 100% of imaged patients [24]. Below the skull base, the vagus nerve is not directly visible by CT and MRI, although its course from the skull base to the carina can be imaged by either modality. Contrast-enhanced CT is typically accessible and conveniently allows complete and rapid imaging of the full extracranial course of the vagus nerve and direct imaging of the larynx and can be extended into the upper thorax to cover the entire course of the left recurrent laryngeal nerve. Cranial Neuropathy


Cranial Neuropathy

Cranial Neuropathy. Radiography Chest Chest radiography is not sufficient for the complete evaluation of thoracic causes that can contribute to vocal cord paralysis. Chest CT is more sensitive, particularly for detecting aortopulmonary window and paratracheal lesions [168]. Radiography can only reveal large lesions in the lung apex or mediastinum that may cause CN X deficits but fails to detect small clinically relevant lesions or pathology in the aortopulmonary window and the paratracheal region that can contribute to vocal cord paralysis [158,168]. US Neck US is not able to fully image the entire course of CN X in the posterior fossa or the recurrent laryngeal nerve extending into the upper thorax, both of which can be simultaneously imaged with contrast-enhanced neck CT extended through the AP window [157,158]. US is a complementary modality that can be used to guide biopsies of lesions in the neck that contribute to a CN X palsy [158]. Transcutaneous laryngeal US is an innovative, noninvasive technique that may be suitable to directly assess vocal cord movement in select patients at high risk for iatrogenic vocal cord palsy following surgery or intubation [169-174]. Variant 7: Unilateral isolated weakness or paralysis of the sternocleidomastoid and trapezius muscles (accessory nerve, CN XI). Initial imaging. The accessory nerve (CN XI) consists of a small cranial root originating from the nucleus ambiguous within the medulla oblongata and a large spinal root originating from the ventral horn of the spinal cord, between the C1 and C5 levels. The two components join and enter the pars vascularis of the jugular foramen [2]. The accessory nerve supplies portions of the sternocleidomastoid muscle and the upper portion of the trapezius muscle. Accessory nerve palsy is clinically manifested by weakness and atrophy of these muscles, causing decreased shoulder abduction, shoulder pain, cosmetic disfiguration, and disability.


Cranial Neuropathy

Cranial Neuropathy. Isolated accessory nerve palsy is typically iatrogenic (due to injury from surgery or internal jugular vein cannulation) or may be due to trauma [175]. Accessory nerve palsy can also be accompanied by variable palsies of the glossopharyngeal (CN IX), vagus (CN X), and hypoglossal nerves (CN XII) in combined syndromes, particularly from lesions arising in the brainstem or jugular foramen, as discussed in Variant 9. CT Head There is no relevant literature to support the use of routine CT head alone in the evaluation of unilateral isolated CN XI palsy. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the evaluation of unilateral isolated CN XI palsy. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the evaluation of unilateral isolated CN XI palsy. CT Neck Accessory nerve palsy is clinically manifested by weakness and atrophy of the sternocleidomastoid muscle and trapezius muscle and, as an isolated palsy, is typically due to iatrogenic injury. Contrast-enhanced CT neck may be useful to characterize lesions in the carotid space or posterior cervical space along the extracranial course of CN XI, as well as demonstrating atrophy of the trapezius or sternocleidomastoid muscles. MRI offers superior soft tissue contrast to demonstrate denervation changes or directly image features of neuritis and offers the benefit of being able to directly image the intracranial and high cervical portions of the nerve [2]. Imaging protocols should include thin-cut high-resolution bone windows through the posterior skull base. Noncontrast neck CT offers limited evaluation of the neck and may be an alternate option for this clinical scenario. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CTA Head and Neck There is no relevant literature to support the use of CTA in the evaluation of unilateral isolated CN XI palsy.


Cranial Neuropathy

Cranial Neuropathy. MRA Head and Neck There is no relevant literature to support the use of MRA in the evaluation of vasculature in unilateral isolated CN XI palsy. Cranial Neuropathy Contrast-enhanced modified balanced SSFP sequences and MRA focused on the posterior skull provide detailed imaging of the lower CNs within the jugular foramen and as they exit the skull base [24]. Thin-cut high-resolution heavily T2-weighted imaging combined with MRA provides variable direct visualization of CN XI with the cranial segment identified in 88% of the sides and the spinal segment identified in 93% of the sides in one study [149]. Another study reported lower rates with the spinal root of CN XI visualized in 51% of subjects using contrast- enhanced modified balanced SSFP sequences [24]. Contrast-enhanced modified balanced SSFP sequences and MRA focused on the posterior skull provide detailed imaging of the lower CNs within the jugular foramen and as they exit the skull base [24]. Thin-cut high-resolution heavily T2-weighted imaging combined with MRA provides variable direct visualization of CN XI with the cranial segment identified in 88% of the sides and the spinal segment identified in 93% of the sides in one study [149]. Another study reported lower rates with the spinal root of CN XI visualized in 51% of subjects using contrast- enhanced modified balanced SSFP sequences [24]. MRI offers excellent soft tissue contrast to directly image features of neuritis or nerve sheath tumors as well as fully characterize the carotid space and posterior cervical space [2]. In patients with accessory nerve palsy, atrophy, and denervation, signal changes can be seen in the trapezius muscle on MRI [2,176]. US Neck The accessory nerve can be directly imaged by US within the posterior cervical triangle and can provide a supportive role in the diagnosis of spinal accessory nerve injuries, although sensitivity may be user dependent [177-180]. Variant 8: Unilateral isolated weakness or paralysis of the tongue (hypoglossal nerve, CN XII).


Cranial Neuropathy

Cranial Neuropathy. Initial imaging. The hypoglossal nerve (CN XII) nucleus arises in the dorsal medulla. The hypoglossal rootlets traverse the premedullary cistern dorsal to the vertebral artery and then form the nerve, which enters the hypoglossal canal where it is surrounded by a venous plexus. The extracranial hypoglossal nerve travels caudally within the carotid space after which it courses anteriorly inferior to the hyoid where it distributes terminal branches providing somatic motor innervation to the intrinsic and extrinsic muscles of the tongue (except the palatoglossus muscle) and the infrahyoid strap muscles via the ansa cervicalis [2,13,181]. Hypoglossal nerve palsy typically presents clinically when a nuclear or infranuclear lesion is present and is characterized by dysarthria and deviation of the tongue to the side of the lesion upon tongue protrusion. Hypoglossal nerve palsy can occur because of injury of the nerve at any point along its course. There are a multitude of causes for hypoglossal nerve palsy including brainstem infarct, demyelinating disease, tumors, vascular lesions, trauma, inflammatory, and infectious processes. Nuclear lesions are usually accompanied by additional neurologic deficits indicative of brainstem involvement. Most hypoglossal nerve palsies are due to neoplasm involving the hypoglossal canal [2,182,183]. Within the extracranial segment, the most common causes of isolated hypoglossal nerve palsy are malignant tumors both along the course of CN XII Cranial Neuropathy in the carotid space and in the sublingual space [184]. Dissection of the internal carotid artery can result in isolated acute CN XII palsy or multiple variable patterns of CN palsies including involvement of CN IX through CN XII [185-187]. Associate denervation signal alterations can be seen on MRI that vary with the duration of the palsy [2,186-188].


Cranial Neuropathy

Cranial Neuropathy. Hypoglossal nerve palsy can also be accompanied by variable palsies of the glossopharyngeal (CN IX), vagus (CN X), and accessory nerves (CN XI) in combined syndromes, particularly from lesions arising in the brainstem or jugular foramen, as discussed in Variant 9 [183]. CT Head There is no relevant literature to support the use of routine CT head alone in the initial evaluation of unilateral isolated CN XII palsy. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the initial evaluation of unilateral isolated CN XII palsy. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the initial evaluation of unilateral isolated CN XII palsy. CT Neck Evaluation of the entire course of the hypoglossal nerve is required with a hypoglossal nerve palsy. MRI is useful for evaluating hypoglossal nerve palsy, directly imaging the brainstem, the intracranial and skull base segments of the hypoglossal nerve and assessing for possible lesions along the extracranial segments of the nerve while providing improved soft tissue contrast [5,13,181,183,189]. The extracranial segment of the hypoglossal nerve within the suprahyoid neck is difficult to see with MRI and CT and inferred by knowledge of the nerve course and surrounding anatomy. Neck CT provides complementary information to MRI, characterizing the osseous integrity of the hypoglossal canal and surrounding skull base [183]. Imaging protocols should include thin-cut high-resolution bone windows through the posterior skull base. Contrast should be administered, because tumors are the most common cause of isolated hypoglossal nerve palsy in this segment. Noncontrast CT may also be an alternate option for this clinical scenario. There is no relevant literature to support the use of combined pre- and postcontrast imaging.


Cranial Neuropathy

Cranial Neuropathy. For detecting hypoglossal canal invasion by glomus tumors, CT had a sensitivity and specificity of 87.5% and 66.7%, respectively, compared with MRI which had a sensitivity of 100% and a specificity of 59% [183]. CTA Head and Neck When dissection of the internal carotid artery is clinically suspected as a cause of acute isolated CN XII palsy, CTA may be useful to evaluate for dissection, particularly in the emergent setting. In a study comparing CTA with conventional angiography, CTA had a sensitivity of 66% when evaluating for blunt carotid vascular injury, with most false-negatives representing low grade injuries [190]. In a comparative study, multidetector CT/CTA demonstrated more features of cervical artery (internal carotid and vertebral arteries) dissection compared with MRI/MRA. There was no significant reader preference for MRI/MRA compared with CT/CTA when evaluating for internal carotid artery dissection. MRI/MRA provided additional characterization of ischemic complications [191]. In a retrospective review of the literature comparing test performance of MRI/MRA with CTA in the assessment of cervicocephalic arterial dissection with a reference standard of catheter angiography, the authors report MRI sensitivities and specificities of 50% to 79% and 67% to 99%, respectively, and CTA sensitivities and specificities of 51% to 98% and 67% to 100%, respectively (based on prospective studies) [192]. The authors concluded that the test characteristics of MRI/MRA and CTA for diagnosis of cervicocephalic arterial dissection were similar and study selection should be based on individual factors including urgency of imaging. A limitation of the literature assessing MRA and CTA for dissection is that most studies evaluate test performance in the clinical setting of traumatic dissection rather than spontaneous dissection. CTA is often used as a primary screening tool when carotid dissection is suspected in the emergent setting [190].


Cranial Neuropathy

Cranial Neuropathy. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT skull base to mid-thigh in the initial evaluation of unilateral isolated CN XII palsy. Cranial Neuropathy MRA Head and Neck When dissection of the internal carotid artery is suspected as a cause of acute isolated CN XII palsy, MRA may be useful to evaluate for dissection. In a retrospective review of the literature comparing test performance of MRI/MRA with CTA in the assessment of cervicocephalic arterial dissection with a reference standard of catheter angiography, the authors report MRI sensitivities and specificities of 50% to 79% and 67% to 99%, respectively, and CTA sensitivities and specificities of 51% to 98% and 67% to 100%, respectively (based on prospective studies) [192]. The authors concluded that the test characteristics of MRI/MRA and CTA for diagnosis of cervicocephalic arterial dissection were similar and study selection should be based on individual factors including urgency of imaging. In another comparative study, multidetector CT/CTA demonstrated more features of cervical artery (internal carotid and vertebral arteries) dissection compared with MRI/MRA. There was no significant reader preference for MRI/MRA compared with CT/CTA when evaluating for internal carotid artery dissection. MRI/MRA provided additional characterization of ischemic complications [191]. A limitation of the literature assessing MRA and CTA for dissection is that most studies evaluate test performance in the clinical setting of traumatic dissection rather than spontaneous dissection. CTA is often used as a primary screening tool when carotid dissection is suspected in the emergent setting [190]. MRI had greater sensitivity (100%) but lower specificity (59%) for detecting hypoglossal canal invasion by glomus jugulare tumors when compared with CT (sensitivity of 87.5% and specificity of 66.7%) [183].


Cranial Neuropathy

Cranial Neuropathy. Denervation injury changes that occur within the tongue in the setting of hypoglossal nerve palsy vary with acuity and can be detected on MRI and CT, with MRI providing better soft tissue contrast [186-188]. Thin-cut heavily T2-weighted contrast- enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves with 90% to 100% of imaged CN XII visible [24]. MRI had greater sensitivity (100%) but lower specificity (59%) for detecting hypoglossal canal invasion by glomus jugulare tumors when compared with CT (sensitivity of 87.5% and specificity of 66.7%) [183]. Denervation injury changes that occur within the tongue in the setting of hypoglossal nerve palsy vary with acuity and can be detected on MRI and CT, with MRI providing better soft tissue contrast [186-188]. Thin-cut heavily T2-weighted contrast- enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves with 90% to 100% of imaged CN XII visible [24]. Cranial Neuropathy US Neck There is no relevant literature to support the use of US neck in the initial evaluation of unilateral isolated CN XII palsy. Variant 9: Multiple different lower cranial nerve palsies or combined lower cranial nerve syndromes (CN IX-XII). Initial imaging. The medulla oblongata joins the pons to the spinal cord and is composed of a ventral portion and a dorsal tegmentum. The ventral portion contains the pyramids and olives, and the dorsal tegmentum contains CN IX through CN XII nuclei along with the white matter sensory tracts. Vascular supply to the medulla is from the anterior spinal artery, branches of the vertebral arteries, and the posterior inferior cerebellar arteries [1,131]. Outside the brainstem, CN IX through CN XI traverse the jugular foramen, and CN XII traverses the hypoglossal canal in the posterior skull base before extending caudally into the neck.


Cranial Neuropathy

Cranial Neuropathy. Lesions affecting the medulla oblongata, the subarachnoid space, or the posterior skull base, including the jugular foramen and hypoglossal canal, can lead to multiple CN palsies affecting CN IX through CN XII in variable patterns. Patients with medullary lesions will typically have additional neurologic findings such as long tract signs, nystagmus, vertigo, ataxia, nausea, and vomiting. A thorough neurologic examination evaluating for these associated signs can localize a process to the brainstem [18,135]. Imaging protocols can then be tailored to evaluate the suspected region of anatomy affected. Most brainstem syndromes are due to brainstem infarctions and hemorrhages [132]. Wallenberg syndrome or lateral medullary syndrome is typically due to occlusion of the posterior inferior cerebellar artery. Additional disorders that may affect the brainstem include demyelinating disease, primary brainstem tumors, metastasis, encephalitis, Arnold-Chiari malformations, and syringobulbia [18,132]. Multiple different jugular foramen syndromes are described based on variable patterns of CN palsies affecting CN IX through CN XII and include Vernet syndrome (IX, X, XI), Collet-Sicard syndrome (IX, X, XI, XII), and Villaret syndrome (IX, X, XI, XII and cervical sympathetic trunk). Lesions affecting the jugular foramen leading to jugular foramen syndromes include jugular foramen tumors (paragangliomas, schwannomas, and meningiomas), infection, leptomeningeal processes, metastasis, trauma, cholesteatoma, and vascular lesions [147,148,193]. Dissection of the internal carotid artery can result in isolated acute CN XII palsy or less commonly multiple variable patterns of CN palsies including involvement of CN IX through CN XII [185-187]. Leptomeningeal processes can lead to variable patterns of cranial neuropathy [18,132]. CT Head There is no relevant literature to support the use of routine head CT in the initial evaluation of multiple lower CN palsies.


Cranial Neuropathy

Cranial Neuropathy. CT Maxillofacial There is no relevant literature to support the use of maxillofacial CT in the initial evaluation of multiple lower CN palsies. CT Temporal Bone There is no relevant literature to support the use of temporal bone CT in the initial evaluation of multiple lower CN palsies. CT Neck Multiple different jugular foramen syndromes can result in variable patterns of CN palsies affecting CN IX through CN XII. Lesions involving the jugular foramen can extend caudally in the neck to involve the carotid space. CT is complementary to MRI in assessing jugular foramen lesions or for evaluating for carotid space lesions. Thin-cut high-resolution bone algorithm windows are useful to delineate skull base fractures, hyperostosis, skull base erosion, intratumoral calcification, and the bony margins of the jugular foramen and nearby skull base foramina [144-148]. Contrast should be administered. There is no relevant literature to support the use of combined pre- and postcontrast imaging. CTA Head and Neck Most brainstem syndromes are due to brainstem infarctions and hemorrhages, which are best imaged with MRI [132]. CTA may be complementary to CT or MRI to characterize the vasculature in these clinical scenarios. Cranial Neuropathy When dissection of the internal carotid artery is clinically suspected as a cause of multiple lower CN palsies, CTA may be useful to evaluate for dissection, particularly in the emergent setting. In a study comparing CTA with conventional angiography, CTA had a sensitivity of 66% when evaluating for blunt carotid vascular injury, with most false-negatives representing low grade injuries [190]. In a comparative study, multidetector CT/CTA demonstrated more features of cervical artery (internal carotid and vertebral arteries) dissection compared with MRI/MRA. There was no significant reader preference for MRI/MRA compared with CT/CTA when evaluating for internal carotid artery dissection. MRI/MRA provided additional characterization of ischemic complications [191].


Cranial Neuropathy

Cranial Neuropathy. In a retrospective review of the literature comparing test performance of MRI/MRA with CTA in the assessment of cervicocephalic arterial dissection with a reference standard of catheter angiography, the authors report MRI sensitivities and specificities of 50% to 79% and 67% to 99%, respectively, and CTA sensitivities and specificities of 51% to 98% and 67% to 100%, respectively (based on prospective studies) [192]. The authors concluded that the test characteristics of MRI/MRA and CTA for diagnosis of cervicocephalic arterial dissection were similar and study selection should be based on individual factors including urgency of imaging. Limitations of the literature assessing MRA and CTA for dissection include most studies evaluate test performance in the clinical setting of traumatic dissection rather than spontaneous dissection. CTA is often used as a primary screening tool when carotid dissection is suspected in the emergent setting [190]. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT skull base to mid-thigh in the initial evaluation of multiple lower CN palsies. MRA Head and Neck Most brainstem syndromes are due to brainstem infarctions and hemorrhages [132]. MRA may be complementary to MRI to characterize the vasculature in these clinical scenarios. When dissection of the internal carotid artery is clinically suspected as a cause of multiple lower CN palsies clinically, MRA may be useful to evaluate for dissection although it is less accessible emergently compared with CTA. In a comparative study, multidetector CT/CTA demonstrated more features of cervical artery (internal carotid and vertebral arteries) dissection compared with MRI/MRA. There was no significant reader preference for MRI/MRA compared with CT/CTA when evaluating for internal carotid artery dissection. MRI/MRA provided additional characterization of ischemic complications [187].


Cranial Neuropathy

Cranial Neuropathy. In a retrospective review of the literature comparing test performance of MRI/MRA with CTA in the assessment of cervicocephalic arterial dissection with a reference standard of catheter angiography, the authors report MRI sensitivities and specificities of 50% to 79% and 67% to 99%, respectively, and CTA sensitivities and specificities of 51% to 98% and 67% to 100%, respectively (based on prospective studies) [188]. The authors concluded that the test characteristics of MRI/MRA and CTA for diagnosis of cervicocephalic arterial dissection were similar and study selection should be based on individual factors including urgency of imaging. Limitations of the literature assessing MRA and CTA for dissection include most studies evaluate test performance in the clinical setting of traumatic dissection rather than spontaneous dissection. CTA is often used as a primary screening tool when carotid dissection is suspected in the emergent setting [186]. Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves within the jugular foramen, and their relationship to the hypoglossal nerve as they exit the skull base, with 90% to 100% of imaged CN IX, CN X, and CN XII visible [24]. There is variable direct visualization of CN XI with the cranial segment identified in 88% of the sides and the spinal segment identified in 93% of the sides in one study [149]. Another study reported lower rates with the spinal root of CN XI visualized in only 51% of subjects using heavily T2-weighted contrast-enhanced modified balanced SSFP sequences [24]. Cranial Neuropathy DWI can be used to assess for acute brainstem infarction, cholesteatoma, and for characterizing tumor cellularity. False-negative DWI can occur in the setting of very small ischemic brainstem infarcts [137,138].


Cranial Neuropathy

Cranial Neuropathy. Thinner slice axial DWI or thin-section coronal DWI may improve sensitivity for detecting small acute brainstem infarction, with nearly 25% of acute brainstem infarcts more easily seen on thin-cut coronal DWI compared with standard axial DWI in one study [138,194]. Thin-cut heavily T2-weighted contrast-enhanced modified balanced SSFP sequences and contrast-enhanced MRA focused on the posterior skull provide detailed imaging of the lower nerves within the jugular foramen, and their relationship to the hypoglossal nerve as they exit the skull base, with 90% to 100% of imaged CN IX, CN X, and CN XII visible [24]. There is variable direct visualization of CN XI with the cranial segment identified in 88% of the sides and the spinal segment identified in 93% of the sides in one study [149]. Another study reported lower rates with the spinal root of CN XI visualized in only 51% of subjects using heavily T2-weighted contrast-enhanced modified balanced SSFP sequences [24]. DWI can be used to assess for acute brainstem infarction, cholesteatoma, and for characterizing tumor cellularity. False-negative DWI can occur in the setting of very small ischemic brainstem infarcts [137,138]. Thinner slice axial DWI or thin-section coronal DWI may improve sensitivity for detecting acute brainstem infarction, with nearly 25% of acute brainstem infarcts more easily seen on thin-cut coronal DWI compared with standard axial DWI in one study [138,194]. US Neck There is no relevant literature to support the use of US neck in the initial evaluation of multiple lower CN palsies. Variant 10: Head and neck cancer. Suspected or known perineural spread of tumor. Initial imaging. The compact anatomy of the brainstem results in close proximity of multiple CN nuclei, and the complex anatomy of the head and neck results in close proximity and interconnection of multiple CNs, which can lead to multiple cranial neuropathies. Multiple middle and lower CN palsies are discussed in Variant 4 and 9, respectively.