Orbital diseases may cause partial or complete monocular visual loss (scotoma) because of optic nerve (I) involvement. Diplopia may be due to oculomotor (III), trochlear (IV), and abducens (VI) nerves dysfunctions. Intraorbital apical CN III lesion associates ptosis and mydriasis when the ciliary ganglion that receives afferent parasympathetic fibers is affected.

Superficial and deep facial lesions may cause trigeminal neuropathy when the extracranial branches of CN V are injured. Specific signs may suggest particular branches, especially when unilateral: hypoesthesia, numbness, or burning of the forehead (V1), the chick (V2), the jaw (V3.); diminished or absent corneal reflex (ophthalmic branch V1); atrophic or weak muscles of mastication (motor branch V3). Facial pain is a very unspecific sign but numbness, progressive symptoms and motor weakness should always be taken seriously and are frequently linked to a structural lesion.

Perimastoid and parotid lesion may cause an extracranial CN VII dysfunction with isolated peripheral facial nerve palsy but preserved lacrimal function, stapedius reflex and taste in the anterior two thirds of the tongue.

In the suprahyoid region, CN IX to XII have close relationships explaining why they are often injured simultaneously. Association of CN IX and X disorder is frequent and result in otalgia, dysphagia, absent gag reflex, uvular deviation away from the side of the lesion, endolaryngeal symptoms (hoarseness, dysphagia in cervical esophagus, vocal cord palsy), loss of taste to the posterior 1/3 of the tongue, tachycardia or bradycardia, etc. Isolated disorders of CN XI and XII are common. CN XI palsy is suggested on shoulder drop and inability to raise the arm. CN XII palsy is diagnosed on deviation of the tongue to the side of the lesion, amyotrophy of the intrinsic and extrinsic tongue muscles, and orobuccal dysarthria.

In the infra-hyoid region, lesions would result in an isolated CN X injury and vagus related oropharyngeal signs will be absent and only the endolaryngeal symptoms will be present. Muscle denervation atrophy is an indirect sign of involvement of the motor cranial nerves and should always be checked [25].

Besides the above mentioned lesions, neural disorders also occur in case of vasculitides, neurotoxin, after radiotherapy.

Because of the large spectrum of extracranial diseases, here are presented most common etiologies.

#### **12.6.1 Vascular Lesions**

Intraorbital cavernous hemangioma is an ovoid welldelineated enhancing lesion in the orbit and can compress the optic nerve (Fig. 12.5). Venous varix can be recognized on flow void, vascular enhancement, and size increase on procubitus.

Internal carotid artery dissection or (pseudo)aneurysm may cause deficits of the lower cranial nerves IX–XII, due to the compression on the nerves into the carotid space (Fig. 12.6). These nerves can also be damaged during endarterectomy.

Aneurysms of the aortic arch and even cardiomegaly can cause irritation of the left recurrent laryngeal nerve [26].

#### **12.6.2 Infectious Diseases**

Aggressive bacterial and fungal infections arising from sinuses, temporal bone, and skull base can insult the adjacent cranial nerves. Aspergillus and mucormycosis can be recognized on the very low signal inside the sinuses on T2-WI and the destruction of the bony walls of the sinuses.

All extracranial cranial nerves close to the sinuses and temporal bone can be affected by fungal infection and aggressive bacterial infection: frontal sinus (V1), ethmoid and sphenoid (II, III, IV, V1, V2, VI—orbital apex and superior orbital fissure), temporal bone (VII). Periapical and periodontal dental disease may cause maxillary (V2) and mandibular (V3) neuropathy which can be seen on postcontrast FS T1-WI or MR neurography [27].

The facial nerve can be involved in malignant otitis externa, a pseudomonas infection in diabetic or immunocompromised patients. Skull base osteomyelitis can also affect the lower cranial nerves IX–XII while mandibular

**Fig. 12.5** (**a**) cavernous hemangioma of the orbital apex revealed by unilateral vision loss, the enhancement of the lesion and relation to the optic nerve is clear on this isotropic 0.55 mm thick post-contrast black blood 3D TSE T1-WI; (**b**) schwannoma of the left maxillary nerve (V2) in the pterygopalatine fossa, as an expansive slightly heterogeneously enhanced on post-contrast T1-WI, scalloping the adjacent bones; (**c**) neurofibromatosis type 2 with multiple schwannomas of the left vagus nerve (X) (white arrow) and the right Meckel cave (gray arrow) on postcontrast coronal T1-WI; (**d**) neurofibromas on paracoronal 3D neurog-

osteomyelitis can cause inferior alveolar nerve irritation with pain and numbness. This mandibular osteomyelitis should be differentiated from osteoradionecrosis. Both will result in loss of the high signal inside the mandible and both can enhance. However, osteoradionecrosis can be distinguished when bone sequesters are present, hypointense defects are seen in the cortex and when periosteal bone is formed.

Abscess formation in the carotid space can cause lower cranial nerve IX–XII symptoms and mediastinitis and mediastinal inflammatory adenopathy can cause left sided CN X or recurrent laryngeal nerve deficits.

#### **12.6.3 Non-infectious Inflammatory Diseases**

#### **<IP_ADDRESS> Demyelinating Diseases**

In young adults, spontaneous vision loss is often due to an optic neuritis, which can be a particular feature of demyelin-

raphy with black blood pulse as bilateral thickening and hyperintensity of both inferior alveolar nerves (V3) (white arrows), external to lingual nerves (gray arrows). (**e**) Perineural tumor spread along the left maxillary nerve (V2) of an epithelial carcinoma of the nostril (gray arrow), post-contrast FS T1 show a thickened enhancing V2 in the pterygopalatine fossa, the rotundum foramen (white arrows); (**f**) post-traumatic left accessory nerve palsy (XI) with sternocleidomastoid (white arrow), trapezius muscles (gray arrow), and levator scapulae (black arrow) muscles degeneration

ating diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd) with anti-AQP4 or anti-MOG antibodies. Accurate diagnosis assessment is needed because of different treatments with potential deleterious effects when inappropriate. Besides clinical and biological data, whole CNS imaging that includes optic nerves is mandatory. Optic nerve lesions are best identified using post-contrast FS T1-WI and 3D-FLAIR.

In MS, optic neuritis is usually unilateral, short, involving the middle portion of the nerve.

In anti-AQP4+, optic neuritis is usually bilateral, long, involving the posterior portion of the nerves with chiasmatic extension.

In anti-MOG+, optic neuritis is usually bilateral, long, involving the anterior portion of the nerves.

Additional CNS imaging abnormalities are helpful for differential diagnosis.

In MS, MRI demonstrates scattered nodules in the brain and the upper half of spinal cord. Spinal lesions are small

**Fig. 12.6** (**a**, **b**) post-traumatic left vision loss, sagittal FS T2 (**a**) shows a retrobulbar edema and an optic nerve hyperintense contusion, optic nerve probabilistic tractography suggests a nerve section of poorer prognosis; (**c**) facial nerves tractography showing the left posterior dis-

placement of the nerve by a parotid cystadenolymphoma; (**d**) hypoglossal nerves tractography showing the contact with the right internal carotid dissection in a patient referred for a painful hypoglossal palsy

extending over <2 vertebral segments on sagittal images, and occupying <50% of the cord diameter of axial images. Dissemination in time accounts for plaques of varied contrast uptake.

In anti-AQP4+, brain lesions are mostly periventricular with a suggestive involvement of the area postrema. Spinal cord lesions are usually located in the upper half of the cord, involving three or more vertebral segments on sagittal images, more than 50% of the cord diameter.

In anti-MOG+, brain lesions are involving more often basal ganglia, thalamus, and the pons. Spinal cord lesions are usually located in the lower half of the cord, involving three or more vertebral segments on sagittal images, more than 50% of the cord diameter [14, 15].

#### **<IP_ADDRESS> Granulomatous Diseases**

Extracranial lesions of various granulomatous diseases, such as Wegener's disease, Langerhans cells and non-Langerhans cells histiocystosis, can insult the anterior optic pathways in association with orbital and naso-sinusal lesions. Involvement of the adjacent orbit can occur with potential optic nerve and/ or maxillary nerve involvement. Intracranial extension following the neural routes is possible.

Optic nerves and anterior optic pathways can be affected in 1–5% of sarcoidosis patients. Sarcoidosis is an inflammatory granulomatosis that can mimic optic nerve meningioma. In these patients careful examination of the systemic signs should lead to the diagnosis. However, bilateral optic nerve involvement, enhancement of the complete optic nerve from the globe to the chiasm, bilateral enlargement of lacrimal and parotid glands, leptomeningitis, and infundibular thickening are imaging signs indicative of sarcoidosis [1, 2, 5, 7].

#### **<IP_ADDRESS> Orbital Pseudotumor**

Orbital pseudotumor is a benign non-infectious inflammatory condition of the orbit. As a diagnosis of exclusion, systemic causes such as infections and neoplasms should be ruled out. Patients present with sudden painful proptosis, ophthalmoplegia (III, IV, VI), vision loss (II), uveitis and retinal detachment. An ill-defined enhancing pseudo-mass involving any area of the orbit is best detected on postcontrast FS T1-WI. A very fast response to corticosteroid treatment is necessary to confirm the diagnosis.

#### **<IP_ADDRESS> Grave's Ophtalmopathy**

Graves' disease is an autoimmune disease affecting the thyroid and Graves' ophtalmopathy is found in more than 25% of the patients. Extraocular muscle hypertrophy and adipogenesis cause increased ocular pressure and proptosis, possible diplopia (extraocular muscle involvement) and vision loss (II).

#### **12.6.4 Tumors**

#### **<IP_ADDRESS> Primary Nerve Lesions**

#### **Esthesioneuroblastoma**

Esthesioneuroblastoma or olfactory neuroblastoma is a rare tumor arising from the olfactory neurosensory receptor cells in the olfactory epithelium of the high nasal vault. Nasal obstruction, rhinorrhea, epistaxis, anosmia, headaches are common. CT and MRI show a dumbbell tissular mass, enhanced on post-contrast images with peripheral cysts. Bone destruction allows spreading into the ethmoid and the sphenoid sinuses, through the cribriform plate and the anterior cranial fossa.

#### **Optic Nerve Glioma**

As the optic nerve is an extension of the brain, primary tumor is an optic nerve glioma, usually a pilocytic astrocytoma. This glioma occurs under the age of 20 years. The typical appearance is a fusiform lesion on the optic nerve with T2 hyperintensity and a variable enhancement. It causes a kinking of the optic nerve and the lesion may reach the optic chiasm. Optic nerve glioma can be associated with neurofibromatosis type I (NF1), especially when bilateral. NF1 associated optic tumors rarely extend beyond the optic pathway and are usually not cyst-like, whereas those not associated with NF1 usually involve the optic chiasm, extend extra-optically, and are frequently cyst-like [28].

#### **<IP_ADDRESS> Nerve Sheath Tumors**

As extracranial extension of CNS, intraorbital optic nerves are surrounded by CSF and meningeal sheath. Optic nerve sheath meningioma appears as a fusiform mass surrounding the optic nerve. Post-contrast T1-WI demonstrates a perineural homogeneous enhancement with a "tram track" appearance. CT may show linear calcifications. CSF may be trapped between the tumor and the eyeball.

Optic nerves and olfactory tracts and bulbs have no Schwann cells. However, the olfactory filia which are connecting the olfactory mucosa with the olfactory bulbs do have Schwann cells and hence "olfactory schwannomas" are reported although they do not originate on the olfactory nerve itself.

All other CN but VIII have an extracranial course with Schwann cells on which nerve sheath tumors can arise, including schwannomas, neurofibromas, and rarely malignant tumors.

They are less often found on the short orbital apex segment of CN III, IV, and VI. The chance to find such tumors on the end branches of the trigeminal nerve (V) is higher (Fig. 12.5) but far less frequent than on its intracranial portion.

Nerve sheath tumors along intraparotid branches of CN VII do occur but one is most frequently dealing with extensions of a mastoid segment lesion into the parotid gland.

Nerve sheath tumors can be detected on all four lower cranial nerves but schwannomas of CN X are most frequent. Extracranial schwannomas of CN XII frequently pass through the hypoglossal canal into subarachnoid space. Extracranial schwannomas of CN IX and XI are rare.

Schwannomas are well-circumscribed, fusiform in shape and have intense enhancement (Fig. 12.5). Cystic, fatty, and hemorrhagic degeneration are possible. Schwannomas are solitary and sporadic in most cases in old adults. However, autosomic dominant neurofibromatosis type 2 (NF2) is likely when multiple schwannomas are present, and bilateral vestibular schwannomas are pathognomonic. In case of hereditary NF2, patients are younger. And the tumoral onset occurs at a younger age than the affected parent.

Schwannomas might be difficult to distinguish them from neurofibromas, discovered at about 20–30 years. Neurofibromas appear as a mild to non-enhancing thickening of a longer segment of the nerve (Fig. 12.5). Similarly, most neurofibromas are solitary and sporadic. However multiple neurofibromas and plexiform neurofibromas almost assure the diagnosis of NF1.

#### **<IP_ADDRESS> Secondary Nerve Involvement**

#### **Head and Neck Malignancies**

Squamous cell carcinomas, adenoid cystic carcinomas, adenocarcinomas, lymphomas, melanomas arising in the face, sinus, orbit, supra- and infra-hyoid neck can all cause displacement of or invasion of the extracranial CN.

The causative tumors can be different in more specific areas like uveal melanoma and retinoblastoma for the optic nerve, esthesioneuroblastoma for the olfactory bulbs and ophthalmic nerve (V1), rhabdomyosarcoma (V3), malignant parotid gland tumors such as adenoid cystic carcinoma and mucoepidermoid carcinoma for the facial nerve (VII) and bronchogenic carcinoma and thyroid malignancies for the infra-hyoid vagus nerve (recurrent laryngeal nerve) (X).

Tumoral infiltration of extracranial nerves could be difficult to see but the presence of a tumor at the CN endpoint or along its extracranial route allows to make the diagnosis. Post-contrast FS T1-WI are helpful to follow thickened enhanced CN. Diffusion tractography is promising for clinical practice, showing nerve displacement and suggesting tumoral infiltration [11] (Fig. 12.6).

It should not be forgotten that the left recurrent laryngeal nerve, branch of the vagus nerve (X), passes through the aortopulmonary window and can therefore be affected by mediastinal adenopathies and malignancies of the aerodigestive tract.

#### **Perineural Tumor Spread**

Adenoid cystic carcinoma, squamous cell carcinoma and lymphoma are the most frequent malignant head and neck lesions with perineural spread, although other malignant tumors also have the potential to follow the cranial nerves [29]. The most frequently involved nerves are the V1 (skin and lacrimal malignancies), V2 (skin, oral and nasal cavity and sinus malignancies) (Fig. 12.5), V3 (oral cavity-sublingual and submandibular gland and masticator space malignancies) [30], VII (parotid malignancies), and rarely the CN XII.

The perineural spread can be seen as an abnormal enhancement and thickening of the nerve on post-contrast FS T1-WI (Fig. 12.5). Comparison with the contralateral nerve facilitates the diagnosis. It is crucial to detect intracranial CN extension as it diminished therapeutic options and result in a poorer prognosis.

CN V and VII have several connections, often involved in perineural tumor spread, which allow tumoral spread along both nerves and their branches. Involvement of the connection between the maxillary nerve (V2) and vidian nerve (VII) at the level of the pterygopalatine fossa is the most frequently involved connection. Hence, the pterygopalatine fossa should always be checked in detail as its involvement often heralds intracranial extension along the above mentioned branches.

#### **Paragangliomas**

Paragangliomas are vascular tumors arising from glomus bodies located along carotid bulb and the vagus nerve in the carotid space, the jugular foramen, and the middle ear cavity. They are easy to recognize on MRA as the typical fast blood flow in the arterial feeders can be recognized on these images, setting the final diagnosis. A "salt-andpepper" appearance on post-contrast T1-WI is also classical (Fig. 12.4). These lesions can cause compression on any of the four lower CN into the carotid space. It is important to detect possible intracranial extension for surgical planning.

#### **Metastases**

Hematogenous metastases from malignant breast, kidney, lung, melanoma, prostate tumors to the head and neck region can involve all extracranial nerves with secondary CN disorders.

In the orbit, metastases from breast carcinomas are most frequent and compression on the nerve by orbital metastases is far more frequent than direct metastasis to the optic nerve itself.

Other CN III–XII can all be directly involved by the above mentioned metastases or indirectly by metastatic lymph nodes. CN involvement is best seen on post-contrast FS T1-WI in both axial and coronal planes.

#### **12.6.5 Trauma**

In addition to skull base fractures that threaten foraminal segment of CN, facial bones fractures may also insult extracranial segment of CN (Fig. 12.6).

Branches of the trigeminal nerve (V) are at risk of injury, especially in case of: orbital roof and superior orbital fissure fracture (V1); orbital floor and inferior orbital fissure fracture (V2), mandible (collum and between the mandibular and the mental foramina) and central skull base fractures (V3).

Optic canal fracture threatens CN II and orbital apex fracture CN III, IV, VI.

CT is needed to identify fractures and bone fragments displacement which damage CN. CN contusions or shears are best seen on MR inversion recovery images through the nerves. Post-traumatic neuropathy can be recognized as thickened hyperintense nerves on MR neurography [8].

CN disorders may also be iatrogenic after sinonasal and periorbital surgery (II, III, IV, VI), tooth implant and mandibular surgery (V3), parotid surgery (VII), etc. Neck dissections can result in lower CN deficits (Fig. 12.5) and surgery in the lower neck can even damage the recurrent laryngeal nerve causing vocal cord palsy. The postsurgical scar formation replaces the fat around the nerves on T1-WI and can enhance in the early postsurgical period.

#### **12.7 Conclusion**

Cranial nerves disorders are frequent and reveal a broad variety of diseases. Imaging investigation has to be conducted in agreement with the medical history and presentation. Imaging CN coverage has to be discussed from nucleus to target. CT and CTA are useful to rule out symptomatic aneurysm and dissection and to better identify skull lesions and calcifications. MRI remains the best imaging modality for CN, and diffusion tractography can illustrate CN structural changes.

#### **Take Home Messages**

**Acknowledgments** We acknowledge the help of Dr. Arnaud Attyé and Dr. Timothée Jacquesson.

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

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**Part II**

**Brain and Spine**

# **Demyelinating Diseases of the CNS (Brain and Spine)**

**13**

Frederik Barkhof and Kelly K. Koeller

#### **Learning Objectives**

#### **Key Points**

Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

UCL Institutes of Neurology and Healthcare Engineering, London, UK

e-mail<EMAIL_ADDRESS>
K. K. Koeller

Section of Neuroradiology, Department of Radiology, Mayo Clinic, Rochester, MN, USA

#### **13.1 Introduction**

Demyelinating disorders of the central nervous system (CNS) that affect the brain and spine have a variety of etiologies and can be separated into primary such as multiple sclerosis (MS) and other idiopathic inflammatory-demyelinating diseases (IIDDs) and secondary (e.g., infectious, ischemic, metabolic, or toxic) diseases. MRI is the imaging modality of choice to assess demyelinating disorders of the brain and the cord and, together with the clinical and laboratory findings, can accurately classify them in most cases [1–3]. This review will highlight the important imaging manifestations of some acquired demyelinating diseases that allow more specific diagnosis.

#### **13.2 Idiopathic Inflammatory-Demyelinating Diseases (IIDDs) of the CNS**

The term IIDD encompasses a broad spectrum of CNS disorders that can be differentiated according to their severity, clinical course, and lesion distribution, as well as their imaging, laboratory, and pathological findings. The spectrum includes monophasic, multiphasic, and progressive disorders, ranging from highly localized forms to multifocal or diffuse variants [2]. Relapsing–remitting (RR) and secondary progressive (SP) MS are the two most common forms of IIDD. MS can also have a progressive course from onset (primary progressive [PP]). Fulminant forms of IIDD include a variety of disorders that have in common the severity of the clinical symptoms, an acute clinical course, and atypical findings on MRI. The classic fulminant IIDD is Marburg disease but is extremely rare. Baló's concentric sclerosis and acute disseminated encephalomyelitis (ADEM) can also present with severe, acute attacks.

Some IIDDs have a restricted topographic distribution, as is the case with neuromyelitis optica spectrum disorders (NMOSD), which can have a monophasic, but more often follows a relapsing course.

F. Barkhof (\*)

#### **13.3 Multiple Sclerosis**

MS is a progressive inflammatory, demyelinating and neurodegenerative autoimmune disease characterized pathologically by perivascular infiltrates of mononuclear inflammatory cells, demyelination, and axonal loss and gliosis, with the formation of focal and diffuse abnormalities in the brain and spinal cord, mainly affecting the optic nerves, brainstem, spinal cord, and cerebellar and periventricular white matter, although cortical and subcortical gray matter damage is also prominent, resulting in chronic progressive disability for the majority of people with the disorder.

The high sensitivity of MRI in depicting brain and spinal cord demyelinating plaques has made this technique the most important paraclinical tool in current use, not only for the early and accurate diagnosis of MS, but also for understanding the natural history of the disease and monitoring and predicting the efficacy of disease-modifying treatments [4].

MRI is the most sensitive imaging technique for detecting MS plaques throughout the brain and spinal cord. Proton density (PD) or T2-weighted MR images (especially acquired using the fluid-attenuated inversion recovery (FLAIR) sequence) show areas of high signal intensity in the periventricular white matter in >90% of MS patients (the remainder may have cord lesions only). MS plaques are generally round to ovoid in shape and range from a few millimeters to more than 1 cm in diameter. They are typically discrete and focal at the early stages of the disease, but become confluent as the disease progresses, particularly in the posterior hemispheric periventricular white matter. MS plaques tend to affect the periventricular and juxtacortical white matter, whereas small vessel ischemic lesions tend to involve the deep white matter more [4]. The total T2 lesion volume of the brain increases by approximately 5–10% each year in the relapsing forms of MS.

Both acute and chronic MS plaques appear hyperintense on T2/FLAIR sequences, reflecting their increased tissue water content. The signal increase indicates edema, inflammation, demyelination, reactive gliosis, and/or axonal loss in proportions that differ from lesion to lesion. The vast majority of MS patients have at least one ovoid periventricular lesion, whose major axis is oriented perpendicular to the outer surface of the lateral ventricles. The ovoid shape and perpendicular orientation derive from the perivenular location of the demyelinating plaques noted on histopathology (Dawson's fingers).

MS lesions tend to affect specific regions of the brain, including the periventricular white matter, the inferior surface of the corpus callosum, the cortico-juxtacortical regions, the temporal lobes, and the infratentorial regions. Focal involvement of the periventricular white matter in the anterior temporal lobes is typical for MS and rarely seen in other white matter disorders, especially not in aging/hypertension (see table below). The lesions commonly found at the calloso-septal interface are best depicted by sagittal T2-FLAIR images—a sequence highly recommended for diagnostic MRI studies.

Characteristic differences between small-vessel disease (SVD) and MS

a With the exception of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Histopathological studies have shown that a substantial portion of the total brain lesion load in MS is located within the cerebral cortex. Presently available MRI techniques are not optimal for detecting cortical lesions because of poor contrast resolution between normal-appearing gray matter (NAGM) and the plaques in question, and because of the partial volume effects of the subarachnoid spaces and CSF surrounding the cortex. Cortical lesions are better visualized by 2D or 3D FLAIR sequences and newer MR techniques such as 3D double inversion recovery (DIR) MR sequences which selectively suppress the signal from white matter and cerebrospinal fluid (CSF). Juxtacortical lesions that involve the "U" fibers are seen in two-thirds of patients with MS.

Posterior fossa lesions preferentially involve the floor of the fourth ventricle, the middle cerebellar peduncles, and the brainstem. Most brainstem lesions are contiguous with the cisternal or ventricular CSF spaces, and range from large confluent patches to solitary, well-delineated paramedian lesions or discrete "linings" of the CSF border zones. Predilection for these areas is a key feature that helps to identify MS plaques and to differentiate them from focal areas of ischemic demyelination and infarction that preferentially involve the central pontine white matter.

Approximately 10–20% of T2 hyperintensities are also visible on T1-weighted images as areas of markedly decreased signal intensity compared with gray matter. These so-called T1 black holes have a different pathological substrate that depends, in part, on the lesion age. Temporary hypointensity is present in up to 80% of recently formed lesions and probably represents marked edema, with or without myelin destruction or axonal loss. In most cases, the acute lesions become isointense within a few months as inflammatory activity abates, edema resolves, and reparative mechanisms like remyelination become active. Less than 40% evolve into persisting or chronic "black holes" [5], which correlate pathologically with the most severe demyelination and axonal loss, indicating areas of irreversible tissue damage. Chronic black holes are more frequent in patients with progressive disease than in those with RRMS disease, and more frequent in the supratentorial white matter as compared with the infratentorial white matter. They are rarely found in the spinal cord and optic nerves.

MS lesions of the spinal cord resemble those in the brain. The lesions can be focal (single or multiple) or diffuse, and mainly affect the cervical cord segment. On sagittal scans, the lesions characteristically have a cigar shape and rarely exceed two vertebral segments in length (the so-called shortsegment lesions in contrast to longitudinally extensive lesions in NMO). On cross-section, they typically occupy the lateral and posterior white-matter columns, border the surface but may extend to involve the central gray matter, and rarely occupy more than one half the cross-sectional area of the spinal cord [6].

Acute spinal cord lesions can produce a mild to moderate mass effect with some spinal cord swelling and may show contrast enhancement. Active lesions are rarer in the spinal cord than the brain and are more frequently associated with new clinical symptoms. The prevalence of spinal cord abnormalities is as high as 74–92% in established MS, and depends on the clinical phenotype of MS. Asymptomatic spinal cord lesions are found in 30–40% of patients with a clinically isolated syndrome (CIS), even if the presenting symptoms do not involve the spinal cord clinically. In RRMS, the spinal cord lesions are typically multifocal. In secondary progressive MS, the abnormalities are more extensive and diffuse and are commonly associated with spinal cord atrophy. In primary progressive MS, spinal cord abnormalities are quite extensive as compared with brain abnormalities. This discrepancy may help to diagnose primary progressive MS in patients with few or no brain abnormalities.

Longitudinal and cross-sectional MR studies have shown that the formation of new MS plaques is often associated with contrast enhancement, mainly in the acute and relapsing stages of the disease [7]. The gadolinium enhancement varies in size and shape, usually lasting a few weeks, although steroid treatment shortens this period. Incomplete ring enhancement on T1-weighted gadolinium-enhanced images with the open border facing the gray matter of the cortex or basal ganglia is a common finding in active MS plaques and is a helpful feature for distinguishing between inflammatory-demyelinating lesions and other focal lesions such as tumors or abscesses which will have a closed ring of enhancement [8].

Contrast enhancement is a relatively good predictor of further enhancement and of subsequent accumulation of T2 lesions, but shows no (or weak) correlation with progression of disability and development of brain atrophy. In RRMS and early SPMS, enhancement is more frequent during relapses and correlates well with clinical activity. For patients with primary progressive MS, serial T2-weighted studies show few new lesions and less frequent enhancement. Contrast-enhanced T1-weighted images are routinely used in the study of MS to provide a measure of inflammatory activity in vivo.

MRI-based disease activity is 5–10 times more frequently than clinical evaluation of relapses, suggesting that most of the enhancing lesions are clinically silent. Subclinical disease activity with contrast-enhancing lesions is 4–10 times less frequent in the spinal cord than the brain, a fact that may be partially explained by the large volume of brain as compared with spinal cord. High doses of gadolinium and a long post-injection delay can increase the detection of active spinal cord lesions.

The diagnosis of MS relies heavily on MRI information, certainly when there is a clinically isolated syndrome suggestive of demyelination. MRI can be used to show dissemination in space (lesions 2 of 4 locations - juxtacortical, periventricular, infratentorial or spinal cord) and to demonstrate dissemination in time (enhancement or new t2 lesions at follow-up).

#### **13.4 Multiple Sclerosis Variants**

#### **13.4.1 Baló's Concentric Sclerosis**

Baló's concentric sclerosis is a rare IIDD subtype, considered a variant of MS, with characteristic radiologic and pathologic features. The disease was formerly considered an aggressive MS variant, leading to death in weeks to months after onset, and in which the diagnosis was made on histopathologic findings at postmortem examination. However, with the widespread use of MRI, this MS variant is often identified in patients who later have a complete or almost complete clinical recovery [9]. The pathologic hallmarks of are large demyelinated lesions showing a peculiar pattern of alternating layers of preserved and destroyed myelin. One possible explanation for this pattern is that sublethal tissue injury is induced at the edge of the expanding lesion, which would then stimulate expression of neuroprotective proteins to protect the rim of peri-plaque tissue from damage, thereby resulting in alternating layers of preserved and non-preserved myelinated tissue [10]. These alternating bands are best identified with T2-weighted sequences, which typically show thick concentric hyperintense bands corresponding to areas of demyelination and gliosis, alternating with thin isointense bands corresponding to normal myelinated white matter. This pattern can be also identified on T1-weighted images as alternating isointense (preserve myelin) and hypointense (demyelinated) concentric rings. These bands, which may eventually disappear over time, can appear as multiple concentric layers (onion-skin lesion), as a mosaic, or as a "floral" configuration. The center of the lesion usually shows no layering because of massive demyelination ("storm center"). Restricted diffusion followed by contrast enhancement is common in the outer rings (inflammatory edge) of the lesion.

The Baló pattern on MRI can be isolated, multiple, or combined with typical MS-like lesions, and the lesion structure can vary from one or two to several alternating bands, with a total size from one to several centimeters. Lesions occur predominantly in the cerebral white matter, although brainstem, cerebellum, and spinal cord involvement has also been reported [11].

#### **13.4.2 Neuromyelitis Optica Spectrum Disorders**

Neuromyelitis optica (NMO) is an autoimmune inflammatory disorder of the CNS with a predilection for the optic nerves and spinal cord [12]. The discovery of an NMOspecific autoantibody directed against aquaporin-4 (AQP4-Ab), the major water channel in the CNS, clearly identified NMO as a disease separate from MS—and requiring a different treatment than MS [13, 14].

This uncommon and topographically restricted form of IIDD is characterized by severe unilateral or bilateral optic neuritis and complete transverse myelitis, which occur simultaneously or sequentially over a varying period (weeks or years). The index events of new-onset NMO are severe unilateral or bilateral optic neuritis, acute myelitis, or a combination of these symptoms. The myelitis attacks appear as complete transverse myelitis with severe bilateral motor deficits, sensory-level, bowel and bladder dysfunction, pain and significant residual neurologic injury. Optic neuritis attacks are generally more severe than those typically seen in MS.

Approximately 85% of patients have a relapsing course with severe acute exacerbations and poor recovery, which leads to increasing neurologic impairment and a high risk of respiratory failure and death due to cervical myelitis. Patients who experience acute optic neuritis and transverse myelitis simultaneously or within days of each other are much more likely to have a monophasic course. On the other hand, a relapsing course correlates with NMO-IgG seropositivity, a longer interval between attacks, older age at onset, female gender, and less severe motor impairment after the myelitic onset. Although the initial attacks are more severe in patients proven to have monophasic NMO, the long-term neurologic prognosis is somewhat better in this group because patients do not accumulate disability from recurrent attacks.

Clinical features alone are insufficient to diagnose NMO; CSF analysis and MRI are usually required to confidently exclude other disorders. CSF pleocytosis (>50 leukocytes/ mm3 ) is often present, while oligoclonal bands are seen less frequently (20–40%) than in MS patients (80–90%). AQP4-Ab detection is best performed using cell-based assays that have greater sensitivity. AQP4-Ab distinguish this form of IIDD from MS and it can predict relapse and conversion to NMO in patients presenting with a single attack of longitudinally extensive myelitis. NMO-IgG is positive in 52% of patients with relapsing transverse myelitis and in 25% of patients with recurrent idiopathic optic neuritis [15].

Wingerchuk et al. [16] proposed a revised set of criteria for diagnosing NMO. These criteria remove the absolute restriction on CNS involvement beyond the optic nerves and spinal cord, allow any interval between the first events of optic neuritis and transverse myelitis, and emphasize the specificity of longitudinally extensive spinal cord lesions on MRI and NMO-IgG-seropositive status. More recently the International Panel for NMO Diagnosis developed new diagnostic criteria that define the unifying term NMOSD, which is stratified by serologic testing (with or without AQP4-IgG) [17]. These new criteria require, in patients with AQP4-IgG, core clinical and MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. However, more stringent clinical and MRI criteria are required for diagnosis of NMO-spectrum disorders without AQP4-IgG or when serologic testing is unavailable.

#### **Diagnostic Criteria for NMOSD Without or Unknown AQP4-IgG Status**

	- a. At least one core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
	- b. Dissemination in space (two or more different core clinical characteristics)
	- c. Fulfillment of additional MRI requirements, as applicable (see below)

#### **Additional MRI Requirements**

	- a. Normal findings or only nonspecific white matter lesions
	- b. Optic nerve MRI with T2w-hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm

MRI of the affected optic nerve demonstrates swelling and loss of blood–brain barrier integrity with gadolinium enhancement that can extend into the optic chiasm. The spinal cord lesions in NMO typically extend over three or more contiguous vertebral segments and occasionally the entire spinal cord (longitudinally extensive spinal cord lesions); they are centrally located (preferential central gray-matter involvement) and affect much of the cross-section on axial images. During the acute and subacute phase, the lesions are tumefactive and show contrast uptake. In some cases, the spinal cord lesions are small at the onset of symptoms, mimicking those of MS, and then progress in extent over time. The presence of very hyperintense spotty lesions on T2-weighted images ("bright spotty sign") is a specific feature that helps differentiate NMO from MS, particularly in patients without longitudinally extensive spinal cord lesions [6, 11, 12], and likely reflects the highly destructive component of the inflammatory lesion. Spinal cord lesions can progress to atrophy and necrosis and may lead to syrinx-like cavities on T1-weighted images.

NMO was long considered a disease without brain involvement, and a negative brain MRI at disease onset was considered a major supportive criterion for the diagnosis of NMO. However, various studies have shown that brain MRI abnormalities exist in a significant proportion (50–85%) of patients [18]. Brain MRI lesions are often asymptomatic, but sometimes are associated with symptoms even at disease onset. The brain lesions are commonly nonspecific. They can be dot-like or patchy, <3 cm in diameter, and located in the deep white matter, brainstem, or cerebellum. Nonetheless, some brain MRI features appear to be quite characteristic and distinct from MS lesions. These abnormalities may parallel sites with high AQP4 expression adjacent to the ventricular system at any level, such as the hypothalamus, periependymal areas surrounding the third and lateral ventricles, cerebral aqueduct, corpus callosum, and dorsal brainstem adjacent to the fourth ventricle. The appearance of periventricular lesions in NMO is quite characteristic. In contrast to MS, where periventricular lesions are discrete, oval-shaped, and perpendicular to the ependymal lining due to their perivenular distribution (Dawson's fingers), NMO lesions are not oval-shaped, located immediately adjacent to the lateral ventricles following the ependymal lining in a disseminated pattern, and are often edematous and heterogeneous [18]. As opposed to what occurs in MS, NMO lesions do not affect the cortical gray matter.

Involvement of the corpus callosum has been described in 18% of AQP4-seropositive NMO patients. The lesions are multiple, large, and edematous, show heterogeneous signal intensity on T2-weighted images, and sometimes affect the entire thickness of the corpus callosum.

Lesions may also affect areas where AQP4 expression is not particularly high, such as the corticospinal tracts. These lesions, which can be unilateral or bilateral and may affect the posterior limb of the internal capsule and cerebral peduncle of the midbrain, are contiguous and often longitudinally extensive [19].

Other brain MRI findings described in NMO include extensive and confluent hemispheric white-matter lesions and radial hemispheric lesions (sometimes corresponding to an extension of periventricular lesions), which are likely related to vasogenic edema involving the white-matter tracts. These lesions usually do not show mass effect or contrast enhancement, but there may be a "cloud-like" pattern of enhancement, defined as multiple patches of enhancing lesions with blurred margins [18]. In fact, the finding of large hemispheric lesions in a patient suspected of MS should trigger the option of NMO and testing for AQP4 antibodies.

Some of the typical brain MRI findings may be specific to clinical presentations, such as intractable vomiting and hiccup (linear dorsal medullary lesions involving the area postrema and nucleus tractus solitarius), or a syndrome of inappropriate antidiuretic hormone secretion (hypothalamic and periaqueductal lesions) [18].

Distinguishing NMO from MS is critical, particularly in the early stages, since the treatment and prognosis of these disorders differ. In fact, some evidence suggests that MS-modifying treatments such as interferon-ß, natalizumab, and laquinimod exacerbate NMO. By contrast, several immunosuppressants (e.g., azathioprine, rituximab, mitoxantrone) seem to help in preventing NMO relapses.

NMOSD can be associated with systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome). Whether the neurologic manifestations are solely due to NMO-spectrum disorder or are a manifestation of these diseases is controversial, although optic neuritis and transverse myelitis are rare presentations of them, and several studies have shown that patients with systemic autoimmune diseases and NMO-IgG-positive antibodies always have optic neuritis, myelitis, or NMO.

#### **13.4.3 Acute Disseminated Encephalomyelitis (ADEM)**

ADEM is a severe, immune-mediated inflammatory disorder of the CNS that predominantly affects the white matter of the brain and spinal cord. In the absence of specific biologic markers, the diagnosis of ADEM is based on clinical and radiologic features [20]. This disorder affects children more commonly than adults, and, in contrast to MS, shows no gender preponderance. The estimated incidence is 0.8 per 100,000 population per year. In most cases, the clinical onset of disease is preceded by viral or bacterial infections, usually nonspecific upper-respiratory-tract infections. ADEM may also develop following a vaccination (postimmunization encephalomyelitis). Patients commonly present with nonspecific multifocal symptoms, which developed subacutely over a period of days, frequently associated with encephalopathy (relatively uncommon in MS), defined as an alteration in consciousness (e.g., stupor, lethargy) or a behavioral change unexplained by fever, systemic illness, or postictal symptoms. Although ataxia, encephalopathy, and brainstem symptoms are frequently present in both pediatric and adult cases, certain signs and symptoms appear to be age-related. In childhood ADEM, long-lasting fever and headaches occur more frequently, while in adult cases, motor and sensory deficits predominate. In general, the disease is self-limiting and the prognostic outcome favorable.

Although ADEM usually has a monophasic course, multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from MS. This multiphasic form, which accounts for <4% of ADEM cases, is defined as a new encephalopathic event consistent with ADEM, separated by 3 months after the initial illness but not followed by any further events. The second ADEM event can involve either new or re-emergent neurologic symptoms, signs, and MRI findings. Relapsing disease following ADEM that occurs beyond a second encephalopathic event is no longer consistent with multiphasic ADEM but rather indicates a chronic disorder, most often leading to the diagnosis of MS or NMO [21] and should prompt testing for myelin oligodendrocyte glycoprotein (MOG) antibodies, especially in children.

An ADEM event as the first manifestation of the classic relapsing form of MS occurs in 2–10%. According to the International Pediatric Multiple Sclerosis Study Group, the diagnosis of MS is met if, after the initial ADEM, a second clinical event meets the following three requirements: (1) it is non-encephalopathic; (2) it occurs 3 months or more after the incident neurologic illness; and (3) it is associated with new MRI findings consistent with the McDonald criteria for dissemination in space [21]. The presence of hypointense lesions and two or more periventricular lesions are MRI features that support an MS diagnosis in children with acute CNS demyelination [21]. Unlike the lesions in MS, ADEM lesions are often large, patchy, and poorly marginated on MRI, especially when there are MOG antibodies [22]. There is usually asymmetric involvement of the subcortical and central white matter and cortical gray–white junction of the cerebral hemispheres, cerebellum, brainstem, and spinal cord. Lesions confined to the periventricular white matter and corpus callosum are less common than in MS. The gray matter of the thalamus and basal ganglia is often affected, particularly in children, and typically in a symmetric pattern [23]. However, the frequency of thalamic involvement in adult ADEM does not differ from that of adult MS. This can be explained by the fact that involvement of this structure is less common in adult ADEM than in childhood ADEM. Four patterns of cerebral involvement have been proposed to describe the MRI findings in ADEM [24]: (1) ADEM with small lesions (<5 mm); (2) ADEM with large, confluent, or tumefactive lesions, and frequent extensive perilesional edema and mass effect; (3) ADEM with additional symmetric deep gray-matter involvement; and (4) acute hemorrhagic encephalomyelitis. Gadolinium enhancement of one or more lesions occurs in 14–30% of cases [21]. The pattern of enhancement varies and can be complete or incomplete ringshaped, nodular, gyral, or spotty. Although ADEM is usually a monophasic disease, new lesions may be seen on follow-up MRI within the first month of the initial attack.

Most MRI lesions appear early in the course of the disease, supporting the clinical diagnosis of ADEM. Nonetheless, in some cases, there may be a delay of more than 1 month between the onset of symptoms and the appearance of lesions on MRI. Therefore, a normal brain MRI scan obtained within the first days after the onset of neurologic symptoms suggestive of ADEM does not exclude this diagnosis.

The spinal cord is affected in <30% of ADEM patients [24], predominantly in the thoracic region. The spinal cord lesion is typically large, causes swelling, and shows variable enhancement. In most ADEM patients, partial or complete resolution of the MRI abnormalities occurs within a few months of treatment. This course is positively associated with a final diagnosis of ADEM.

#### **13.5 Infectious Inflammatory Demyelinating Disorders**

#### **13.5.1 Progressive Multifocal Leukoencephalopathy**

Progressive multifocal leukoencephalopathy (PML) is overwhelmingly a disease of the immunocompromised patient and most (55–85%) cases are related to acquired immunodeficiency syndrome (AIDS). There is a wide age range of involvement, with the peak age of presentation in the sixth decade. The disease is caused by reactivation a papovavirus (JC virus) that selectively attacks the oligodendrocyte, leading to demyelination. Treatment with monoclonal antibody therapy (natalizumab, rituximab, efalizumab) or other immunomodulatory drugs, commonly used in patients with MS and other disorders has also been linked with PML [25]. Untreated patients with PML have an extremely poor prognosis, with death common in the first 6 months following establishment of the diagnosis. Although there is no specific treatment, combination anti-retroviral therapy (cART) has not only resulted in a lower incidence of PML in AIDS patients, but also substantially improved survival times of afflicted patients, now at 50% 1-year survival [25]. Unfortunately, about 20% of PML cases are linked to a robust inflammatory response to pathogens associated with recovery of the immune system after a period of immunosuppression. This condition, known as PML-IRIS (Immune Reconstitution Inflammatory Syndrome), has been associated with intracranial masses with generous amounts of surrounding vasogenic edema on MRI. Enhancement may also occur [25].

The lesions of PML are characterized by little mass effect or enhancement. Most lesions involve the subcortical white matter and deep cortical layers of the parieto-occipital or frontal white matter, although gray matter and posterior fossa lesions are also common, occurring in up to 50% of cases. PML lesions tend to be more confluent in their appearance than ADEM lesions and scalloping of the lateral margin of the lesion at the gray matter-white matter junction is common. Subtle signal intensity changes in the white matter may precede clinical suspicion of the PML-IRIS. While development of mass effect and temporary enhancement in the early phase of cART has been linked to better survival, similar imaging manifestations may also be seen in monoclonalantibody treated PML patients [25].

#### **13.5.2 Human Immunodeficiency Virus Encephalopathy**

Human immunodeficiency virus (HIV) encephalopathy results from direct infection of the brain by the virus itself. Since the advent of cART, the prevalence of the disease has markedly decreased and the temporal progression has been slowed. Most patients are severely immunocompromised at the time of onset and exhibit psychomotor slowing, impaired mental status, and memory difficulties. Histologically, demyelination and vacuolation with axonal loss are noted, along with occasional microglial nodules. Mild cerebral atrophy is the first and sometimes only imaging feature of AIDS dementia complex, also know as HIV dementia, HIV-associated dementia complex, or as HIV-associated neuron-cognitive disorder (HAND). Involvement of the central white matter, basal ganglia, and thalamus is characteristic. Typically, bilaterally symmetric abnormal T2 hyperintensity in the basal ganglia and small focal areas in the periventricular regions are noted on T2-weighted MR images [26]. Regression of these findings has been seen following institution of cART.

#### **13.6 White Matter Disease from Toxic Imbalance**

#### **13.6.1 Chronic Alcohol Ingestion and its Consequences**

Brain abnormalities in alcoholics include atrophy, Marchiafava–Bignami disease, Wernicke encephalopathy, osmotic myelinolysis, and consequences of liver cirrhosis such as hepatic encephalopathy and coagulopathy [27]. All the reported entities are not specific of alcohol and can be found in many other toxic or metabolic conditions. Ethanol direct brain toxicity is caused by under-regulation of receptors of N-methyl-D-aspartate, abnormal catabolism of homocysteine, resulting in an increased susceptibility to glutamate excitatory and toxic effects. Moreover, immune response occurs mediated by lipid peroxidation products that bind to neurons resulting in neurotoxicity. Neuroimaging studies show a characteristic distribution of loss of volume: initially there is infratentorial predominance with atrophy of the cerebellar vermis and hemispheres. Frontal and temporal atrophy is subsequently evident, followed by diffuse atrophy of the brain. The possibility of partial reversibility of these alterations is also observed. In pregnancy, ethanol determines inhibition of maturation of Bergmann's fibers of cerebellum, with consequential marked cerebellar atrophy.

#### **13.6.2 Hepatic Encephalopathy**

The term *hepatic encephalopathy* (HE) includes a wide spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction. Most cases are associated with cirrhosis and portal hypertension or portal-systemic shunts, but the condition can also be seen in patients with acute liver failure and rarely, those with portal-systemic bypass and no associated intrinsic hepatocellular disease. Although HE is a clinical condition, several neuroimaging techniques, particularly MRI, may eventually be useful for the diagnosis because they can identify and measure the consequences of CNS increase in substances, which, under normal circumstances, are efficiently metabolized by the liver. Classical MR abnormalities in chronic HE include high signal intensity in the globus pallidum on T1-weighted images, likely a reflection of increased tissue concentrations of manganese, and an elevated glutamine/glutamate peak coupled with decreased myo-inositol and choline signals on proton MR spectroscopy, representing disturbances in cell-volume homeostasis secondary to brain hyperammonemia [28]. Recent data have shown that white matter abnormalities, also related to increased CNS ammonia concentration, can also be detected with several MRI techniques: magnetization transfer ratio measurements show significantly low values in otherwise normal-appearing brain white matter, T2-Flair sequences reveal diffuse and focal high signal intensity lesions in the hemispheric white matter, and DWI discloses increased white matter diffusivity. All these MR abnormalities, which return to normal with restoration of liver function, probably reflect the presence of mild diffuse interstitial brain edema, which seems to play an essential role in the pathogenesis of HE.

In acute HE, bilateral symmetric signal-intensity abnormalities on T2-weighted images, often with associated restricted diffusion involving the cortical gray matter, are commonly identified. Involvement of the subcortical white matter and the basal ganglia, thalami, and midbrain may also be seen. These abnormalities that can lead to intracranial hypertension and severe brain injury reflect the development of cytotoxic edema secondary to the acute increase of brain hyperammonemia.

#### **13.6.3 Marchiafava–Bignami Disease**

Marchiafava–Bignami disease is a rare complication of chronic alcoholism, characterized by demyelination and necrosis of the corpus callosum, with rare involvement of extracallosal regions. Etiology remains unknown but is believed to be caused by toxic agents in red wine of low quality and lack of group B vitamins. Rarely, the disease has also been reported in non-alcoholic patients. Symptoms are mainly represented by cognitive deficits, psychosis, hypertonia, and interhemispheric disconnection, until coma and death. Typical MRI features in the acute phase are corpus callosum hyperintensity on T2-weighted sequences and FLAIR, without significant mass effect, with peripheral enhancement. Diffusion is restricted due to cytotoxic edema. In chronic forms, necrosis of the genu and splenium can be detected [29].

#### **13.6.4 Wernicke Encephalopathy**

Wernicke encephalopathy is an acute condition first described by the French ophthalmologist Gayet in 1875, and later by the German neurologist Wernicke in 1881, caused by a deficiency of B1 (thiamine). It develops frequently but not exclusively in alcoholics. Other potential causes include extended fasting, malabsorption, digitalis poisoning, massive infusion of glucose without B1 in weak patients. The autoptic incidence is reported to be 0.8–2% in random autopsies, and 20% in chronic alcoholics. The classic clinical triad of ocular dysfunctions (nystagmus, conjugate gaze palsy, ophthalmoplegia), ataxia, and confusion is observed in only 30% of cases. Treatment consists of thiamine infusion, and avoids irreversible consequences including Korsakoff dementia or death. Memory impairment and dementia are related to damage of the mammillary bodies, anterior thalamic nuclei and interruption of the diencephalic-hippocampal circuits. Depletion of thiamine leads to failure of conversion of pyruvate to acetyl-CoA and α-ketoglutarate to succinate, altered pentose monophosphate shunt, and the lack of Krebs cycle, with cerebral lactic acidosis, intra- and extra-cellular edema, swelling of astrocytes, oligodendrocytes, myelin fibers, and neuronal dendrites. Neuropathological aspects include neuronal degeneration, demyelination, hemorrhagic petechiae, proliferation of capillaries and astrocytes in peri-aqueductal gray substance, mammillary bodies, thalami, pulvinar, III cranial nerves nuclei, and cerebellum. On MRI, bilateral and symmetrical hyperintensities on T2-weighted sequences and FLAIR are evident at the level of the already mentioned structures, mainly mammillary bodies and thalami [30, 31]. Rarely, cortex of the forebrain can be involved. DWI shows areas of reduced apparent diffusion coefficient (ADC) due to cytotoxic edema, although the ADC can sometimes be high due to the presence of vasogenic component. Rarely, T1-weighted images show bleeding ecchymotic hemorrhages in the thalami and mammillary bodies, a sign considered clinically unfavorable. In 50% of cases, contrast enhancement is present in periaqueductal regions. Marked contrast enhancement of mammillary bodies is evident in 80% of cases, even prior to the development of visible changes in T2-weighted sequences and is considered highly specific for WE. In chronic forms, change of signal in T2-weighted sequences becomes less prominent due to the diffuse brain atrophy, more pronounced at the level of mesencephalon and mammillary bodies.

#### **13.6.5 Osmotic Demyelination Syndrome**

Osmotic demyelination syndrome (ODS) usually occurs in the setting of osmotic changes, typically with the rapid correction of hyponatremia. This causes destruction of the blood–brain barrier with hypertonic fluid accumulation in extracellular space, resulting in a non-inflammatory demyelination. The most common damage is in the pontine fibers [32]. ODS is observed in alcoholics with nutritional deficiency. The most common symptoms include paralysis, dysphagia, dysarthria, and pseudobulbar palsy. Death is frequent. Rarely, ODS affects other regions, especially basal ganglia, thalami, deep white matter. MRI usually shows an area of high signal on T2-weighted sequences in the central part of the pons (central pontine myelinolysis), sparing ventro-lateral portions and corticospinal tracts. The lesion is moderately hypointense in T1 and may show positive contrast enhancement. If the patient survives, the acute phase can evolve into a cavitated pontine lesion.

#### **13.7 White Matter Disease Associated with Radiation Therapy and Chemotherapy**

Treatment strategies designed to target cancer cells are commonly associated with deleterious effects to multiple organ systems, including the CNS. As both radiation and chemotherapy alone can be associated with significant toxicity, the combination of radiation and chemotherapy may be particularly harmful to the CNS. With advanced treatment regimens and prolonged survival, neurological complications are likely to be observed with increasing frequency.

Neurotoxicity can result from direct toxic effects of the drug or radiation on the cells of the CNS, or indirectly through metabolic abnormalities, inflammatory processes, or vascular adverse effects.

Recognition of treatment-related neurologic complications is critically important, because symptoms may be confused with metastatic disease, tumor progression, paraneoplastic disorders, or opportunistic infections, and discontinuation of the offending drug may prevent irreversible CNS injury.

#### **13.7.1 Radiation Injury and Necrosis**

It is widely accepted that the white matter of the CNS is prone to radiation-induced injury, compared with gray matter. Radiation encephalopathy has been classically divided into three stages according to its timing after radiotherapy: early, early-delayed, and late-delayed reactions [33]. Within the first several weeks of therapy, patients may experience acute declines with focal neurologic deficits. These effects are possibly related to increased edema, which has been supported by the observation that steroid treatment often results in clinical improvement. Early-delayed adverse effects usually occur within 1–6 months of treatment and are thought to be a result of demyelination. This syndrome is characterized by somnolence, fatigue, and cognitive dysfunction, consistent with dysfunction of the frontal network systems. Late-delayed side effects occur months to years after cessation of treatment and are largely irreversible and progressive. These late changes are commonly associated with progressive cognitive deficits. In more severe cases of late-delayed radiation injury, imaging and histopathological studies may demonstrate leukoencephalopathy and/or focal necrosis.

In all types of white matter radiation-induced damage, CT and mainly MRI may demonstrate variable degrees of white matter signal changes related to an increase in free tissue water in the involved areas. This may result from endothelial damage, causing increased capillary permeability and vasogenic edema, or from demyelination. However, the degree of these white matter changes correlates poorly with the functional deterioration observed in the patients. MRI findings in early reactions occurring during course of treatment are nonspecific. MRI may be normal or demonstrate poorly defined multifocal lesions in both hemispheres that usually disappear spontaneously. MRI in early-delayed reactions also may show signal changes involving not only the hemispheric white matter but also the basal ganglia and the cerebral peduncles, which resolve completely without treatment. These early-delayed changes have been reported in children with acute lymphatic leukemia who have been treated with both whole brain irradiation and chemotherapy. These changes have no correlation with clinical manifestations and have no clear prognostic significance. Late-delayed reactions can be subdivided into diffuse and focal radiation necrosis injury.

Diffuse radiation injury is characterized by white matter changes that are "geographic" in nature, i.e., the areas of abnormal signal intensity or attenuation are limited to the regions of the brain that conform to the radiation portal. This can produce striking differences between the involved zones and the spared surrounding white matter. The involved territories are often symmetric and do not enhance on post-contrast studies. While originally reported in children with leukemia, diffuse necrotizing leukoencephalopathy has also been observed following treatment for many other malignancies in both children and adults. The disease may occur following chemotherapy alone, but the incidence of disease is highest when chemotherapy is combined with radiation therapy. Both the histologic findings and imaging features bear resemblance to radiation necrosis. Axonal swelling, demyelination, coagulation necrosis, and gliosis dominate the histologic picture.

Diffuse white matter changes, with hypoattenuation on CT and T1 and T2 prolongation on MRI, are common and often involve an entire hemisphere. Microbleeds can occur as a sign of vasculopathy. Radiation-induced leukoencephalopathy may be associated with progressive brain atrophy, and patients may present with cognitive decline, gait abnormalities, and urinary incontinence. However, the more common mild-to-moderate cognitive impairment is inconsistently associated with radiological findings, and frequently occurs in patients with normal-appearing scans. Recently, more sensitive tools to quantify the damage to brain tissue, such as diffusion tensor imaging (DTI) have been applied in patients treated with brain radiotherapy and have shown early and progressive diffuse changes in normal-appearing white matter indicating radiationinduced demyelination and mild structural degradation of axonal fibers, which are undetectable with conventional MRI.

Focal radiation necrosis usually manifests as a ring-like or irregular enhancing mass lesion located in the white matter, which may become hemorrhagic. The MRI features commonly seen in radiation necrosis include a soap bubblelike interior and Swiss cheese-like interior. Compared with lesions with the soap bubble pattern, Swiss cheese lesions are larger, more variable in size, and more diffuse. This pattern can be visualized as a result of diffuse necrosis affecting the white matter and cortex with diffuse enhancement at the margins with intermixed foci of necrosis. The rim of enhancement is often thinner, more uniform, and more aligned to the gray matter-white matter junction than in malignant tumors. As radiation necrosis progresses, it can lead to severe shrinkage of the white matter and cortex and result in focal brain atrophy with hydrocephalus.

Quite frequently is impossible to distinguish radiation necrosis from recurrent malignant brain tumor, such as glioblastoma multiforme, using conventional MRI. Metabolic imaging (e.g., positron emission tomography) may facilitate differentiating between the two diseases as radiation necrosis is iso-to-hypometabolic while recurrent high-grade tumors are typically hypermetabolic. MR spectroscopy (MRS) may also be useful as radiation necrosis frequently shows a characteristic lactic acid peak and near-normal peaks for N-acetylaspartate (NAA) and choline while recurrent high-grade gliomas typically show elevated choline levels compared to NAA without or with elevated lactic acid levels. Perfusion imaging can identify the areas of increased blood flow associated with tumor recurrence, whereas radiation necrosis is not expected to contain any increased blood flow [34].

#### **13.7.2 Chemotherapy-Associated Neurotoxicity**

Neurotoxicity has been observed with virtually all categories of chemotherapeutic agents [35]. Neurologic complications may range from acute encephalopathy, headache, seizures, visual loss, cerebellar toxicity, and stroke to chronic side effects, including chronic encephalopathy, cognitive decline, and dementia.

Among the most puzzling aspects of cancer therapyrelated toxicity is the occurrence of delayed and progressive neurological decline, even after cessation of treatment. Anticancer agents affect brain function through both direct and indirect pathways. It is also conceivable that additional variables play important roles, including the timing of treatment, combination of different treatment modalities, patient age, integrity of the blood–brain barrier, and cognitive function prior to treatment initiation.

Imaging studies have provided evidence that structural and functional CNS changes occur in a significant number of patients treated with chemotherapy. Some agents, such as methotrexate or carmustine, are well known to cause a leukoencephalopathy syndrome, especially when administered at a high dose, intrathecally, or in combination with cranial radiotherapy. Nonenhancing, confluent, periventricular white matter lesions, necrosis, ventriculomegaly, and cortical atrophy characterize this syndrome. White matter abnormalities following high-dose chemotherapy have been detected in up to 70% of treated individuals and usually have a delayed onset of several months.

A delayed leukoencephalopathy syndrome with distinct DWI abnormalities on MRI indicative of cytotoxic edema within cerebral white matter has been recently described. This syndrome appeared to mimic a stroke-like syndrome and has seen mainly in patients receiving methotrexate, 5-fluorouracil (5-FU), carmofur, and capecitabine.

#### **13.8 Vascular Causes of White Matter Disease**

#### **13.8.1 Posterior Reversible Encephalopathy Syndrome (PRES)**

Although not a truly demyelinating condition, reversible encephalopathy syndrome is noteworthy because of its affinity for the posterior cerebral white matter territories and is important in the differential diagnosis of demyelinating disease. Under normal circumstances, cerebral perfusion pressure is maintained at a relatively constant level by autoregulation, a physiologic mechanism that compensates for wide changes in systemic blood pressure. Hypertensive encephalopathy is believed to result from loss of normal autoregulation, with competing regions of vasodilatation and vasoconstriction, and endothelial dysfunction. The vessels of the posterior cerebral circulation, lacking less sympathetic innervation compared to those of the anterior circulation, are unable to vasoconstrict in a normal manner and bear the brunt of these vascular changes. Reversible vasogenic edema is the result and is associated with visual field deficits, as well as headaches, somnolence, and an overall impaired mental status. The terms posterior reversible encephalopathy syndrome (PRES) and reversible posterior leukoencephalopathy syndrome (RPLS) have been popularized in the literature to describe this scenario that is most commonly seen in hypertensive states and/or the presence of immunosuppression (particularly cyclosporine A and tacrolimus), chemotherapy, eclampsia, and renal failure. While it commonly involves the posterior cerebral white matter, other sites may also be affected including unilateral cerebral hemispheric or isolated brainstem involvement in patients following aortic valve surgery [36, 37]. Accordingly, it has been suggested that perhaps the terminology should be changed to simply "reversible encephalopathy" [38].

On MR studies, bilaterally symmetric abnormal T2 hyperintensity, representing vasogenic edema, is most commonly seen in the distribution of the posterior circulation, although other sites including the frontal lobes and corpus callosum may be noted as well. Cortical and subcortical lesions may be better detected on FLAIR sequences. DWI may be normal or show restricted water diffusion in regions of infarction that correlate with poorer prognosis [23]. Susceptibilityweighted imaging may show areas of hemorrhage within involved territories. With early treatment and limited involvement of the brain, many of these imaging abnormalities will completely resolve and most patients recover within 2 weeks [39]. However, when larger areas or regions of infarction are involved, permanent neurologic deficits or even death are possible. Vascular narrowing has been observed on angiographic studies. Perfusion studies reported in the literature indicate normal to increased perfusion in these zones. When biopsies of these regions have been performed, white matter edema is seen histologically.

#### **13.8.2 Aging and Ischemic Demyelinating Disorders**

Small focal lesions on T2-weighted images are quite common in the white matter of adult subjects [40]. They are not associated with mass effect, do not enhance, and are typically isointense compared to normal white matter on T1-weighted images. When these lesions have been biopsied, histologic examination reveals a spectrum of findings including gliosis, (partial) loss of myelination, and vasculopathy. They tend to be located in the deep white matter of the centrum semiovale. In contrast to MS, lesions do not involve the corpus callosum or the juxtacortical U-fibers, important distinguishing features [3]. Since the lesions are so ubiquitous and appear to be a part of "normal" aging, various terms have been proposed: senescent white matter changes or disease, deep white matter ischemia, leukoaraïosis, etc. In general, the more lesions present, the more likely it is that the patient will have cognitive problems or difficulties with neuropsychological testing. However, it is not possible to predict a particular patient's status simply based on the imaging appearance alone.

In adult patients between 30 and 50 years of age, the presence of periventricular and subcortical lesions in a patient with a family history of similarly affected relatives should raise the possibility of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A defect in the notch3 gene on the long arm of chromosome 19 has been identified and apparently evokes an angiopathy affecting small and medium-sized vessels. Most lesions occur in the frontal and temporal lobes and less commonly in the thalamus, basal ganglia, internal and external capsules, and brain stem [41].

#### **13.9 Conclusion**

MRI of the brain and spinal cord is of vital importance in the diagnosis of MS, the most important idiopathic inflammatory CNS disorder [42]. Dissemination in space and time on MRI is not limited to MS and can occur in NMO, and spinal cord imaging is important in the differential diagnosis. Increasingly, MRI is used to monitor MS treatment and their complications such as PML.

#### **Take Home Message**

• MRI of the brain and the spinal cord should be performed in any patient suspected of MS to show dissemination in space according to McDonald criteria. Additional gadolinium enhancement or new T2 lesions demonstrate dissemination in time and allow a final diagnosis and treatment initiation. Spinal cord MRI with multiple short segment lesions is almost pathognomonic for MS and a negative cord scan is a red flag in MS.

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

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**Part III**

**Pediatric and Fetal**

# **Children with Acute Neurological Emergency**

**14**

Gunes Orman, Andrea Rossi, Avner Meoded, and Thierry A. G. M. Huisman

#### **Learning Objectives**

Children with acute neurological emergencies frequently present to the emergency room (ER) with various combinations of headache, fever, nausea, vomiting, physical signs of trauma, altered mental status, coma, or focal neurological symptoms. Neuroimaging is often needed in children with acute neurological emergencies due to the difficulties of gathering an adequate and comprehensive patient history or a detailed and reliable neurological examination [1]. The radiologist plays an important role in the ER. Firstly, the radiologist should be able to answer if the child needs neuroimaging emergently. Secondly, the radiologist should be able to answer which imaging modality is appropriate for the child. Different imaging modalities may be chosen based on the institutional availability and clinical status of the patient. Computed tomography (CT) and magnetic resonance imaging (MRI) are the most frequently used imaging modalities in the emergency setting. CT is usually the initial modality of choice in most of the situations. Modern multidetector CT scanners render highly detailed multiplanar submillimeter images of the pediatric brain; however, the main disadvantage of CT is that it requires

G. Orman (\*) · A. Meoded · T. A. G. M. Huisman

Edward B. Singleton Department of Radiology, Texas Children's Hospital, Houston, TX, USA

e-mail<EMAIL_ADDRESS>
the use of ionizing radiation [2]. MRI is a valuable tool to confirm and characterize the entities seen in children with acute neurological emergency. MRI is easy to perform, does not use ionizing radiation, offers multiple different tissue contrasts, superior anatomical details, especially for evaluation of the posterior fossa, and offers multiple advanced, and functional sequences enhancing a sensitive and specific diagnosis [2, 3]. These advantages made MRI an increasingly preferred modality for the diagnostic evaluation of children with acute neurological symptoms even in time-sensitive settings. Ultrafast MRI protocols should be considered whenever possible as the initial choice of imaging instead of CT [3, 4]. Advanced MRI techniques including susceptibility-weighted imaging (SWI), diffusion weighted imaging (DWI), or diffusion tensor imaging (DTI) with apparent diffusion coefficient (ADC) mapping and perfusion-weighted imaging (PWI) are progressively used in acute pediatric neuroimaging protocols [2].  In addition, when evaluating brain MRIs of children, the radiologist should be aware that the pediatric brain may be immature and depending on the child's age different states of brain development and maturation may be encountered. A neonatal brain MRI looks very different compared to a teenager's brain MRI. Thus, the radiologist should understand normal brain development and must be familiar with age-specific changes of the developing pediatric brain [2].

The goal of this chapter is to discuss the neuroimaging findings of a number of common acute pediatric neurological emergencies including stroke, hemorrhage, infections, and several less frequently encountered disorders.

#### **14.1 Stroke**

Arterial ischemic stroke (AIS) is relatively rare in children but can lead to significant morbidity and mortality rates ranging between 4% and 14%. Understanding that children with AIS

© The Author(s) 2020 179 J. Hodler et al. (eds.), *Diseases of the Brain, Head and Neck, Spine 2020–2023*, IDKD Springer Series, https://doi.org/10.1007/978-3-030-38490-6\_14

<EMAIL_ADDRESS><EMAIL_ADDRESS>
A. Rossi Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy e-mail<EMAIL_ADDRESS>
present clinically differently than adults and often present with unique child specific risk factors will impact the diagnostic approach, treatment, and outcome. The risk factors for AIS in children include cardiac disorders, infection, head and neck trauma, sickle cell disease, vascular malformations, genetic disorders, and autoimmune diseases [5–7]. The clinical presentation in neonates and infants can be very subtle relative to the severity of imaging findings (Fig. 14.1a). In children with suspected stroke, MRI is the preferred imaging modality. Radiologists should embrace an "MRI first" service whenever possible. Recommended sequences include DWI/DTI and ADC mapping to diagnose acute ischemia, gradient-recalled echo (GRE) or SWI to detect intracranial blood and its breakdown products, and T1-weighted imaging (WI) and T2-WI to assess for myelination, extra-axial blood, and edema [8].

Furthermore, combined analysis of DWI/PWI data can identify tissue at risk of progression to infarction, e.g., "ischemic penumbra" [9]. The penumbra shows critical hypoperfusion without matching diffusion restriction (DWI/PWI mismatch), as opposed to the ischemic core represented by matching areas of hypoperfusion and restricted diffusion. Early and reliable identification of potentially salvageable brain tissue is essential and could serve as a guide to treatment [10].

In addition, simultaneous imaging of the head and neck vasculature should always be considered/included in the acute workup if possible.  In children with AIS rapid treatment with neuroprotection, antithrombotic medications, and potential use of tissue plasminogen activator (tPA) are recommended to limit infarct progression/severity and stroke recurrence [11].

Hemorrhagic venous stroke (VS) may occur as complication of cerebral venous sinus thrombosis (CVST). The most common predisposing factors are systemic or local infection, hypercoagulable state, and dehydration [1]. CVST should be suspected in any child with hemorrhage or brain injury that cannot be explained by an arterial distribution of infarction or history of trauma or infection. If there are features of hemorrhage, additional MR venography (MRV) may be needed to provide diagnostic confidence (Fig. 14.1c). Post-contrast 3D-T1-WI ultrafast GRE sequence may also be helpful to detect venous filling defects [12]. CVST most frequently affects the superior sagittal sinus followed by the transverse sinus, with resulting VS mostly in these venous drainage regions. VS may not demonstrate the same degree of restricted diffusion as AIS due to associated vasogenic edema. Physicians should hold an increased level of clinical suspicion especially in children with risk factors [1]. Rapid imaging and correct diagnosis is very important.

Clinical mimickers of pediatric stroke include systemic hypoglycemia, hemiplegic migraine, seizure, postictal paresis, acute disseminated encephalomyelitis (ADEM), infection and may be seen in up to 21% of children with the initial clinical suspicion of an acute stroke [12–14]. The frequency of these disorders underlines the value of MRI in the emergent evaluation of suspected stroke [12].

#### **Key Point**

• Neuroimaging is extremely time sensitive in children suspected of arterial or venous stroke. MRI with DWI/DTI and ADC is the established imaging modality of choice for the diagnosis.

#### **14.2 Hemorrhages**

Intracranial hemorrhages (ICH) are a frequent cause of severe neurological morbidity and mortality in children. Excluding head trauma which is an important cause of ICH, other causes of spontaneous ICH include arteriovenous malformations (AVM), aneurysms, cavernous malformations, hematological disorders, and brain tumors in children. In addition, ICH may be observed as a complication of AIS and VS. Children may present with headache, vomiting, impaired consciousness, convulsions, and focal neurological deficits. Spontaneous ICH can also present with non-specific symptoms in children especially younger than 3 years of age. Subacute courses are common and may result in a diagnostic delay which may result in a higher mortality and morbidity, especially for infratentorial hemorrhages, in aneurysms, children younger than 3 years and children with underlying hematological disorders [15].

ICH imaging appearances follow a well-known evolution with five distinct phases identified: hyperacute, acute, early subacute, late subacute, and chronic. Neuroimaging findings and appearance vary with the phase (Table 14.1) [16]. On CT, early hyperacute ICH are isodense to normal brain, could be missed if not carefully observed. However, multiplanar reconstructed CT images increase the sensitivity of CT for detection of ICH [17]. Acute and early subacute ICH reveal hyperdensity due to progressive blood clot retraction, while progressive red blood cell lysis decreases the density in the late subacute phase. In the chronic phase, progressive blood resorption results in a hypodense, cerebrospinal fluid (CSF)-filled brain defect. Similar temporal signal changes are observed for the various MRI sequences (Fig. 14.2). The imaging characteristics of ICH are summarized in Table 14.1. T2∗, GRE, or SWI sequences are most sensitive to blood products and should be included in the MRI protocol when ICH are suspected in the emergency setting. Neuroimaging should not only focus on diagnosis of ICH and its complications but should also focus on finding the underlying cause of the ICH. MRA and MRV sequences and contrast-enhanced MRI may be necessary to exclude the underlying cause such as vascular malformations and tumors [16].

**Fig. 14.1** (**a**, top row) In this 25-day old girl with prior surgery for intestinal atresia and recent onset of clonic fits involving the right limbs, axial T2-weighted MRI shows ill-defined cortico-subcortical blurring of the left parietal lobe. Trace DWI and corresponding ADC map clearly reveal restricted diffusion consistent with an acute ischemic stroke involving the posterior portion of the left MCA territory. (**b**, middle two rows) In this 13-year old boy with a subacute presentation with ataxia, coronal FLAIR shows multiple hyperintense areas involving the cerebellum and occipital lobe, suggesting a thromboembolic mechanism involving the posterior circulation. Intracranial TOF MR angiography is normal. Cervical CE-MR angiography, however, shows focal irregularity (arrow) of the left vertebral artery which was confirmed by catheter angiography showing a string-of-beads pattern (arrow) consistent with the eventual diagnosis of fibromuscular dysplasia. (**c**, lower row) In this 16-year-old girl with recent posterior fossa surgery, sagittal T2-W MRI shows deceivingly normal appearance of the superior sagittal sinus, due to hypointense acute thrombus. Contrast-enhanced axial T1-weighted MRI shows the empty delta sign (arrow) consistent with intraluminal sinus thrombosis, which is confirmed by phase contrast MR venography showing absent flow signal involving the totality of the superior sagittal and straight sinuses

**Fig. 14.1** (continued)

*h* hours, *d* days, *m* months

#### **Key Point**

• ICH are a frequent cause of severe neurological morbidity and mortality in children. Depending on the etiology and evolutionary phase of the ICH, CT and/ or MRI imaging characteristics change over time.

#### **14.3 Infections**

Pediatric central nervous system (CNS) infections are high on the list of differential diagnosis when a child present with fever and altered mental status. Neuroimaging is important in the early diagnosis of CNS infections and should be correlated conjunction with laboratory findings. CNS infections may result in significant morbidity and mortality in children [2, 12].

Meningitis is the most common form of bacterial infection of the CNS in children. Causative bacteria vary by age and clinical presentation is different for different age groups. While older children present with fever, headache, photophobia, nausea, vomiting, and meningismus, neonates may present with less obvious vague symptoms. Meningitis is most commonly caused by hematogenous spread from bacterial infections outside of CNS. Less commonly, it develops from an adjacent infective focus, i.e., sinusitis, mastoiditis, or direct invasion after a skull fracture. In general, neuroimaging is not routinely used for the diagnosis of an uncomplicated meningitis, especially if a lumbar puncture already demonstrated an abnormal number of white blood cells in the CSF confirming diagnosis. If there is no complication, neuroimaging may reveal mildly increased meningeal enhancement. Complications of meningitis may however include areas of adjacent vasogenic or cytotoxic edema, focal ischemic injury, CVST, hydrocephalus, and subdural, epidural, or parenchymal abscesses/empyemas. MRI with contrast is the imaging modality of choice to evaluate the complications of bacterial meningitis (Fig. 14.3a–e) [18].

Parenchymal brain infections include cerebritis and cerebral abscess. Symptoms are variable but typically include fever, headache, nausea/vomiting, focal neurological deficits, and seizures. Visual field defects or personality changes can also be seen. If the abscess collection is large, significant mass effect may cause increased intracranial pressure. Neuroimaging is the key to the diagnosis of parenchymal brain infections. MRI with contrast is the most sensitive and specific modality for the radiology diagnosis (Fig. 14.3a–e). Cerebritis may be treated conservatively with intravenous antibiotics, but cerebral abscess requires surgical intervention or drainage [18].

Pyogenic ventriculitis is a life threatening form of CNS infections. The infectious agents are similar to meningitis and abscess. MRI is key to diagnosis; ependymal enhancement after IV contrast injection is usually very prominent. DWI/DTI may show restricted diffusion with **Fig. 14.2** In this 17-year old boy presenting acutely with ictal headache, vomiting, and bradycardia, axial CT (**a**) shows fresh hematoma involving the left parietal lobe with contralateral midline shift and intraventricular blood at the foramen of Monro. CT angiography (**b**) did not reveal abnormal vessels. MRI performed after 12 hours confirms a large intraaxial bleed which is grossly isointense with gray matter on T1-weighted MRI (**c**) and hyperintense on T2-weighted MRI (**d**), consistent with a hyperacute hematoma (prevailing oxyhemoglobin)

reduced ADC values, especially if pus is collecting within the ventricles [18].

Subdural empyema is an infectious fluid collection between dura and arachnoidea (Fig. 14.3a–e). The acute form develops as a result of spread from, e.g., a paranasal sinus infection and is characterized by high fever, headache, meningismus or focal neurological deficits, more rarely seizures. The complications include CVST, cerebral infarction, cerebral edema, or cerebritis. MRI with contrast is the diagnostic modality of choice [18].

Other acute pediatric CNS infections include: (1) viral meningitis and its complications which include ADEM, transverse myelitis, Guillain–Barré syndrome, and cranial neuritis; (2) fungal CNS infections which are most commonly seen in premature or immunocompromised children; and (3) parasitic CNS infections. Early and correct recognition of the neuroimaging findings of these diseases is critical to guide treatment [19].

#### **Key Point**

• The diagnosis of uncomplicated meningitis is usually confirmed with lumbar puncture by demonstrating an increased number of white blood cells in the CSF. Neuroimaging should be saved to evaluate for life threatening complications of meningitis, including empyema or parenchymal infections. MRI with contrast is the diagnostic modality of choice.

**Fig. 14.3** In this 12-year-old boy with suppurative sinusitis (not shown), trace DWI (**a**) and corresponding ADC map (**b**) show right frontal subdural empyema and a focal area of restricted diffusion involving the right frontal lobe, corresponding to an ill-defined hyperintense lesion with perifocal edema and mass effect on T2-W MRI (**c**).

#### **14.4 Trauma**

Traumatic brain injury (TBI) is a significant cause of lifelong disability and mortality in children. The diagnosis of pediatric head trauma requires a multidisciplinary approach. Trauma mechanisms differ from adults and their impact on the developing brain results in unique primary and secondary brain lesions. Birth trauma is responsible for almost all cases of neonatal trauma (parturitional injury); child abuse is a frequent cause of trauma in the first 2 years, whereas falls and motor-vehicle accidents are responsible for the majority of TBI in toddlers and adolescents [20].

Primary TBI lesions include (1) calvarial and maxillofacial fractures; (2) extra-axial: epidural hematoma, subdural

Contrast-enhanced axial T1-weighted MRI (**d**) shows mild, irregular peripheral enhancement consistent with cerebritis, and also reveals ipsilateral arachnoiditis. Follow-up MRI after 4 days (**e**) shows development of a well-defined enhancing ring corresponding to evolution towards a frank abscess

hematoma, subarachnoid hemorrhage, and intraventricular hemorrhage; (3) intraaxial: diffuse axonal injury, cortical contusion, and intracerebral hematoma; and (4) vascular: dissection, carotid cavernous fistula, arteriovenous dural fistula, and pseudoaneurysm. Secondary TBI includes both (1) acute: diffuse cerebral edema, brain herniation (subfalcine, uncal, transtentorial), infarction, or infection and (2) chronic injuries: hydrocephalus, encephalomalacia, CSF leak, and leptomeningeal cyst [21]. Different imaging modalities may identify treatable primary TBI and lead to prevention or limitation of secondary TBI. A recommended minimal standard MRI protocol includes (1) a 3D T1-WI, preferably in the sagittal plane, which allows multiplanar reconstruction, (2) an axial T2-WI, (3) an axial DWI/DTI with ADC mapping,

**Fig. 14.4** In this 12-year-old boy with a severe blunt head trauma, sagittal T1-weighted MRI (**a**) and axial T2-W MRI (**b**) show ill-defined signal abnormality involving the corpus callosum (arrows). SWI (**c**)

reveals more extensive hypointensities consistent with hemorrhagic traumatic axonal injury

and (4) an axial SWI from the skull base to the vertex (Fig. 14.4) [20].

It is important to keep child abuse in mind when dealing with trauma in children in the emergency setting. Abusive head trauma diagnosis is challenging both clinically and radiologically; the provided trauma history might not always reflect the truth and no single imaging finding is specific or diagnostic for abusive head trauma by itself. A multiplicity of trauma related findings and severity of findings inconsistent with the provided mechanism of trauma provide clues for the diagnosis. The radiological findings may vary for different types of injury. The common injury mechanisms related to abusive head trauma can be summarized as non-impact shaking injury, direct impact blunt trauma, whiplash-shaking injury of the craniocervical junction, strangulation injury, and stabbing injury. Further diagnostic workup should include a skeletal survey and possible additional cross-sectional studies to exclude other non-CNS solid organ injury [1, 21].

Spinal cord injury mechanisms in children differ from adults. Vertebral column fractures and spinal cord injuries are less common in children than adults. Pediatric spinal injuries primarily involve the cervical spine mostly in the proximal part including the craniocervical junction [22]. Thoracolumbar fractures often occur at T11 to L2 levels but may also involve other levels. However, if the injury mechanism is of the seat-belt flexion-distraction type, it typically occurs at L2-L4 levels with high association of accompanying visceral injury. In children of all ages, spinal MRI evaluation is important in the setting of unexplained instability, persistent or delayed symptoms, decreased consciousness, or abnormal X-ray or CT findings. MRI findings including spinal cord transection, intramedullary hemorrhage, edema extending over more than one spinal segment, and persistent compression of the spinal cord are predictive of poor neurological outcome [12].

#### **Key Point**

• TBI is a leading cause of lifelong disability and mortality in children. Birth trauma is responsible for many cases of neonatal TBI; child abuse is a frequent cause of TBI in the first 2 years, falls and motor-vehicle accidents are responsible for the majority of TBI in toddlers and adolescents. CT or MRI are the primary diagnostic imaging modalities of choice depending on the etiology of TBI and the age of the child.

#### **14.5 Drowning/Near Drowning**

Drowning is a leading cause of accidental death and severe neurologic morbidity. Anoxic brain injury is a common consequence of non-fatal drowning and may cause severe lifelong disability. Irreversible injury develops in the hippocampi, basal ganglia, and cerebral cortex within 4–10 min following the hypoxic incident. Therefore, early neuroimaging after drowning allows detection of the injury that requires intervention and may also be helpful for the prediction of brain injury severity [23]. CT is usually limited to detect head and neck trauma, but it may detect the loss of gray white matter differentiation and cerebral edema.  MRI especially DWI/DTI with ADC mapping can detect brain injury more reliably, even within minutes after the incident and improves the ability to predict the outcome (Fig. 14.5). Cortical and deep gray matter DWI/ DTI abnormalities and lower ADC values are associated with poor outcomes.

**Fig. 14.5** In this 8-year-old boy with severe anoxia due to neardrowning, trace DWI (**a**) and corresponding ADC map (**b**) show restricted diffusion involving the basal ganglia, thalami, and parieto-

occipital cortex consistent with cytotoxic edema.  MRI with DWI/DTI and ADC mapping should be acquired and evaluated promptly for the children with a drowning history.

#### **14.6 Seizures**

New onset seizures are the most common neurologic emergencies of children presenting to the ER [1, 2]. Seizures are abnormal movements or behavior resulting from abnormal electrical activity in the brain. Acute symptomatic seizures occur at the time of a systemic insult or following brain insult with incidence reaching 29–39/100000 per year. Traumatic brain injury, cerebrovascular disease, drug withdrawal, infarction, and metabolic insults are the most common causes [1, 2]. Unprovoked seizures occur in the absence of precipitating factors, and may be single or recurrent (epilepsy).

A detailed neurological examination with general physical examination and electroencephalogram should be performed initially [1]. Neuroimaging may not be necessary for every child with seizure or epilepsy. For example, neuroimaging is not indicated in children with simple febrile seizures but it should be considered in children with long seizures with focal onset and focal neurological deficits, also it should be strongly considered in neonates with seizures, because an identifiable cause for seizures can be found in up to 90% of full term newborns [1, 2]. When neuroimaging is necessary, MRI is the modality of choice in most of the cases. The aim is to investigate acute focal disorders that need immediate intervention including acute hydrocephalus, acute stroke or hemorrhage, hypoxic ischemic injury in newborns, encephalitis, or tumors. Other relevant disorders include leukodystrophies, metabolic disorders, mesial temporal sclerosis, and malformations [2].

#### **Key Point**

• When dealing with children with seizures in the ER, neuroimaging should be saved for cases with history of long time seizures with focal onset and focal neurological deficits, it should also be strongly considered in neonates with seizures.

#### **14.7 Autoimmune CNS Diseases with Acute Presentation**

Children with autoimmune CNS diseases may also present to the ER with acute signs and symptoms.

ADEM is a monophasic, immune-mediated demyelinating CNS disorder. Patients usually present 1–3 weeks following an upper respiratory infection or vaccination and may present acutely with significant mass effect due to a tumefactive

**Fig. 14.6** (**a**) In this 3-year-old girl with a subacute onset of paraparesis and stupor, axial FLAIR shows ill-defined hyperintensities involving the deep cerebellar and supratentorial white matter. Sagittal T2-weighted MRI of the spine shows quasi-holocord swelling and hyperintensity. After treatment with IVIG and steroids, follow-up MRI at 3 months was normalized (not shown), consistent with acute disseminated encephalomyelitis (ADEM). (**b**) In this 5-year-old girl presenting with headaches and left hemiparesis, trace DWI and corresponding ADC map show a

large right inferior frontal lesion with a necrotic center and an incomplete peripheral ring of restricted diffusion. Another small lesion with similar characteristics is seen in the left parietal lobe. On T2-weighted MRI, the larger lesion shows a concentric onion-bulb appearance. Contrast-enhanced axial T1-weighted MRI shows incomplete peripheral ring enhancement corresponding to the areas of restricted diffusion, consistent with tumefactive demyelination

lesion, with seizures and coma or with behavioral disturbances, headaches, vomiting, fever, or focal neurological signs. Brain MRI typically shows diffuse, poorly demarcated, bilateral, or asymmetrical T2 and FLAIR hyperintense lesions affecting both gray and white matter. The spinal cord may also be involved, showing ill-defined, multiple T2 hyperintense lesions usually involving 2–3 vertebral segments (Fig. 14.6a). ADEM is usually a diagnosis of exclusion.

Multiple sclerosis (MS) is an idiopathic inflammatory disorder characterized by demyelination and degeneration of the CNS, affects most commonly adults, but 3–10% of patients present their first clinical event during childhood. Pediatric onset MS has higher relapse rates and a less favorable prognosis [24]. Therefore, early diagnosis and prompt treatment of pediatric onset MS is necessary (Fig. 14.6b). Ruling out ADEM and neuromyelitis optica spectrum disorder (NMOSD) is important, because although the clinical presentation of these three disorders is similar, the treatment is different in each one. Characteristic MRI criteria of MS on brain MRI are helpful to differentiate MS from ADEM and NMOSD but CSF and serum laboratory findings are also required to confirm the diagnosis [25].

NMOSD is an inflammatory demyelinating disease characterized by optic neuritis and acute longitudinally extending myelitis involving at least three vertebral segments. Most clinical, neuroimaging, and laboratory characteristics of pediatric onset NMOSD are similar to those of adult onset disease [26]. Identification of aquaporin-4 immunoglobulin antibodies serves as an important biomarker for the diagnosis. Longitudinally extending myelitis during an acute attack is T2 hyperintense on sagittal spinal cord MRI with central cord predominance and may matching show contrast enhancement on T1-WI. Optic nerve MRI shows unilateral or bilateral T2 hyperintensity or contrast enhancement on T1-WI within the optic nerve(s) or optic chiasm. Typical brain lesions are T2 hyperintense involving the dorsal medulla, peri-ependymal surfaces of the fourth ventricle, hypothalamus, thalamus, or peri-ependymal surfaces of third ventricle, as well as large, confluent, unilateral or bilateral subcortical or deep white matter lesions or long, diffuse, heterogeneous corpus callosum lesions or long corticospinal tract lesions [26].

#### **Key Point**

• Children with autoimmune CNS diseases may present to the ER with acute signs and symptoms. In addition to CSF and serum laboratory findings, brain and spinal cord MRI is helpful to differentiate MS from ADEM and NMOSD.

#### **14.8 Toxic/Metabolic Imbalances**

Diabetic ketoacidosis (DKA) is an acute serious complication in children with diabetes mellitus type 1. This state may cause significant long-term neurological morbidity and mortality. Brain edema is the most common neuroimaging finding in children with DKA and may cause brain herniation with subsequent cerebral infarctions due to vascular compression. Also, primary ischemic or hemorrhagic stroke during the acute DKA episode may be seen in 10% of cases [27].

Neonatal hypoglycemia is an important issue in term neonates and can cause severe brain injury. Neuroimaging typically shows focal edema or infarcts most commonly in bilateral parieto-occipital lobes, basal ganglia, corpus callosum, and thalami [12]. Because the urine strip test diagnosis of hypoglycemia can be made simply, neuroimaging is usually used to evaluate the degree of brain injury and estimation of prognosis rather than to confirm the diagnosis.

Osmotic demyelination syndrome is an acute demyelination process that usually occurs several days after a rapid change in serum osmolality and is uncommon in children. It can present with central pontine myelinolysis or extrapontine myelinolysis. MRI is the diagnostic modality of choice. Central pontine myelinolysis is seen with characteristic trident-shaped, bat-winged, or piglet hyperintensity on T2-WI, hypointensity on T1-WI with no mass effect in the central pons, with sparing of the ventrolateral pons, tegmentum, and corticospinal tracts. Extrapontine lesions are usually bilateral and most commonly seen in the cerebellar peduncles, globus pallidus, thalamus, lateral geniculate body, putamen, external and extreme capsule, splenium of corpus callosum, and supratentorial white matter [28].

#### **Key Point**

• Neuroimaging with MRI may be necessary when dealing with children with metabolic imbalances in the ER when brain edema is suspected. In addition, MRI is the diagnostic modality of the choice to evaluate the osmotic demyelination syndrome.

#### **14.9 Hydrocephalus**

Hydrocephalus in children could be either due to overproduction of CSF by a tumor, ventricular obstruction, or dysfunctional Pachionic granulations along the subarachnoid space. Children can present to the ER with (1) acute findings of hydrocephalus or (2) complications of shunted hydrocephalus including malfunction and infection.

Clinical presentation of hydrocephalus varies with age; in infants abnormally rapidly increasing head circumference, irritability, vomiting, bulging of the fontanelle; in older children headache, vomiting, diplopia, or papilledema can be seen [29]. Neuroimaging should be directed to identify the underlying cause. MRI is the imaging modality of choice in suspected hydrocephalus cases. Next to axial T1-WI or T2-WI, a thin section, high resolution, T2-WI in sagittal plane is the most helpful MRI sequence to evaluate these cases [1, 2]. Contrast administration would be necessary if a tumor is suspected.

Shunt malfunction is the most common complication of ventricular shunts. Children present with headache, nausea, vomiting, and altered mental status. Multiple radiographs of the skull, neck, chest, and abdomen to evaluate the shunt integrity are often the initial imaging in some institutions [1, 2]. CT is often used as primary cross-sectional imaging because it is readily available, able to detect changes in the ventricular size and configuration, identify intracranial hemorrhages or infarction, shunt catheter discontinuity and catheter migration [2]. Scout views should not be ignored, because occasionally, axial or reconstructed cross-sectional CT images may miss relevant findings. A possible disconnection of a shunt may be within the neck region below or outside of the scanned region; however, the information may be visible on the scout view which is a standard component of each CT study [30]. Children with infection due to a shunted hydrocephalus present with altered mental status, fever, nausea, and vomiting. CSF cultures are usually sufficient for the diagnosis in almost 95% of the cases and neuroimaging has a limited role in the diagnosis [1]. Uncommonly, infection presents with abdominal symptoms from a peritoneal CSF pseudocyst. Abdominal ultrasound or CT is useful to evaluate these cases [2].

**Key Point**

• Children could present to the ER with acute findings of hydrocephalus or complications of shunted hydrocephalus including shunt malfunction and infection. MRI or CT should be used to differentiate the etiology.

#### **14.10 Concluding Remarks**

Children with acute neurological emergency present to the ER with a wide spectrum of symptoms and signs. Neuroimaging is often needed in children with acute neurological emergency due to the difficulties of gathering a good and reliable patient history or limited physical/neurological examination. The radiologist should be able to answer if the child needs neuroimaging emergently, and which imaging modality is appropriate for the child. Different modalities may be chosen based on the institutional availability and clinical status of the patient. CT and MRI are the most frequently used imaging modalities in the emergency setting. Finally, the prompt diagnosis is essential when dealing with children with acute neurological emergency especially in the time sensitive pathologies, i.e., stroke, drowning.

#### **Take Home Messages**

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

**Part IV**

**Head and Neck**

# **Evaluation of Tinnitus and Hearing Loss in the Adult**

Jenny K. Hoang and Laurie A. Loevner

#### **Learning Objectives**

#### **Key Points**

#### **15.1 Introduction**

Tinnitus and hearing loss in the adult can have profound effects on the quality of life. Tinnitus is the perception of sound when no external sound is present and may be described as ringing, buzzing, swishing, or clicking sensations. Hearing

Department of Neuroradiology, Radiology, Neurosurgery, Otorhinolaryngology: Head & Neck Surgery, and Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA

loss ranges from partial to a total inability to hear sounds. Hearing loss and tinnitus can occur concurrently or in isolation. The role of imaging is to help identify the etiology of these symptoms and evaluate for the extent of disease.

#### **15.2 Causes of Tinnitus and Hearing Loss**

#### **15.2.1 Tinnitus**

Tinnitus may be categorized as (1) pulsatile or non-pulsatile, (2) primary (idiopathic) or secondary (due to another condition), and (3) subjective or objective. Evaluation of tinnitus starts with otoscopic examination to determine if there is a vascular retro-tympanic mass, audiometric examination, and review of medical history and medications. This evaluation helps to determine if imaging is necessary and if so, what study(ies) are indicated.

#### **<IP_ADDRESS> Pulsatile Tinnitus**

Causes include vascular masses (glomus tympanicum), aberrant arterial or venous anatomy, vascular malformations, and intracranial hypertension. Objective tinnitus (auscultation of a bruit on physical examination) is uncommon and has been attributed to turbulent flow in the setting of dural fistulas, atherosclerotic carotid artery disease, jugular bulb abnormalities, and large condylar or mastoid emissary veins.

#### **<IP_ADDRESS> Non-pulsatile Tinnitus**

Causes are wide ranging and include cerumen impaction, middle ear infection, mass, medications, noise-induced hearing loss, presbycusis or chronic bilateral hearing loss, hemorrhage, neurodegeneration, and spontaneous intracranial hypotension.

#### **15.2.2 Hearing Loss**

Clinical assessment and audiometric testing can determine the type of hearing loss as conductive, sensorineural, or

**15**

J. K. Hoang (\*)

Department of Radiology and Radiological Science, Russell H. Morgan, Johns Hopkins School of Medicine, Baltimore, MD, USA

L. A. Loevner

mixed and guide subsequent diagnostic imaging. Conductive hearing loss results from diseases affecting the conduction of mechanical sound wave energy to the cochlea. Sensorineural hearing loss is caused by diseases that impair the cochlear function or the transmission of electrical signal along the auditory pathway.

#### **<IP_ADDRESS> Conductive Hearing Loss**

Causes include otospongiosis (commonly mixed), ossicular erosion or fusion, round window occlusion, dehiscence of the superior semicircular canal, and cholesteatoma or neoplasm with suspected intracranial or inner ear extension.

#### **<IP_ADDRESS> Sensorineural Hearing Loss**

Causes include labyrinthine ossificans, vestibular schwannoma, and fractures extending across the otic capsule.

#### **15.3 Anatomy**

The temporal bone forms part of the middle and posterior cranial fossae and is comprised of five parts: petrous, tympanic, mastoid, styloid, and squamous temporal bone. The first three listed parts form the external auditory canal, middle ear, inner ear, and internal auditory canal. These are the segments to review for hearing loss and tinnitus.

#### **15.3.1 External Auditory Canal**

The external auditory canal (EAC) extends from the auricle to the tympanic membrane. The lateral one-third of the EAC is fibrocartilaginous, while the medial two-thirds are surrounded by the tympanic portion of the temporal bone.

#### **15.3.2 Middle Ear**

The middle ear cavity contains the ossicular chain which conducts sound from the tympanic membrane laterally, to the oval window and inner ear structures medially. The roof of the middle ear is the tegmen tympani and the jugular wall is the floor. The middle ear can be subdivided into the epitympanum (attic) superior to the level of the tympanic membrane, mesotympanum at the level of tympanic membrane, and hypotympanum inferior to the level of tympanic membrane. The epitympanum communicates with the mastoid via the aditus ad antrum.

The mesotympanum contains the majority of the ossicular chain. The ossicular chain is composed of three bones: the malleus, incus, and stapes. Since the stapes is anchored to the oval window, a mnemonic for the order of the ossicles is "MISO" representing malleus, incus, stapes, and oval window. The manubrium of the malleus is attached to the tympanic membrane, and the head of the malleus articulates with the body of the incus in the epitympanum forming the incudomalleal joint, which has a characteristic "ice cream cone" configuration on axial sections. The lenticular process of the incus extends at approximately a right angle from the long process of the incus to articulate with the capitulum (head) of the stapes, forming the incudostapedial joint.

An important middle ear structure is the scutum, a sharp bony projection to which the tympanic membrane is attached superiorly. Prussak space, the location for pars flaccida cholesteatomas, is bounded by the scutum laterally and the neck of the malleus medially.

The posterior wall of the middle ear is irregular and includes the sinus tympani, pyramidal eminence, and facial recess.

#### **15.3.3 Inner Ear**

The inner ear comprises the osseous labyrinth, which includes the cochlea, vestibule, and semicircular canals. The cochlea contains the end organ for hearing while the vestibule and semicircular canals are responsible for balance and equilibrium. The densest portion of the temporal bone that surrounds the osseous labyrinth is termed the otic capsule. The osseous labyrinth encapsulates the membranous labyrinth, which contains endolymph and is surrounded by perilymph.

The cochlea is a spiral-shaped structure with 2½–2¾ turns, including the basal, middle, and apical turns, which are separated by interscalar septa. The lateral aspect of the basal turn of the cochlea bulges into the middle ear cavity, forming the cochlear promontory. The nerve of Jacobson (branch of cranial nerve IX) courses over the cochlear promontory. The cochlear nerve passes from the internal auditory canal through the bony canal for the cochlear nerve (also referred to as the cochlear fossette or cochlear aperture) into the modiolus, which is a crown-shaped structure centered within the cochlea that transmits branches of the cochlear nerve to the organ of Corti. The organ of Corti is the end organ for hearing and is not visible on CT images.

The bony vestibule is an ovoid space located superior and posterior to the cochlea, which connects to the semicircular canals. There are three semicircular canals—superior, posterior, and lateral which are oriented orthogonal to one another. The endolymphatic duct extends from the posterior aspect of the vestibule toward the posterior cranial fossa, and ends in a blind pouch, the endolymphatic sac, at the posterior margin of the petrous ridge. The bony vestibular aqueduct surrounds the endolymphatic duct and normally measures up to 1 mm at the midpoint and 2 mm at the operculum, according to the Cincinnati criteria [1].

The cochlear aqueduct should not be mistaken for a fracture. It is a narrow bony channel that surrounds the perilymphatic duct and extends from the basal turn of the cochlea to the subarachnoid space adjacent to the pars nervosa of the jugular foramen.

#### **15.3.4 Internal Auditory Canal**

The internal auditory canal (IAC) is a channel in the petrous bone. It extends from the fundus which abuts the labyrinth to the porus acusticus. At the fundus, a transverse crest (crista falciformis) divides the IAC into superior and inferior compartments. A vertical crest ("Bill's bar") divides the superior compartment into anterior and posterior components. The facial nerve is located in the anterosuperior compartment, the cochlear nerve in the anteroinferior compartment, and the superior and inferior vestibular nerves in the superoposterior and inferoposterior compartments, respectively. A mnemonic for the location of the nerves in the anterior compartment is "Seven (cranial nerve VII) Up Coke (cochlear nerve) down."

#### **15.4 Imaging Modalities and Techniques**

While CT is often the first modality utilized to assess suspected pathology involving the inner ear structures (cochlea and labyrinth), certain lesions such as a cochlear schwannoma and labyrinthine hemorrhage are better detected with MRI. In the work-up of subjective pulsatile tinnitus, CT is frequently the preferred modality. However, MR imaging with MRA and MRV may be more appropriate in the workup of objective pulsatile tinnitus (audible bruit on auscultation by the clinician). Conventional catheter angiography may then follow to further characterize the vascular abnormality as well as to provide therapeutic management (embolization) of lesions such as dural fistulas. MR imaging is the primary modality for evaluating the non-osseous components of the temporal bone, suspected retrocochlear pathology, and sensorineural hearing loss. Magnetic resonance imaging is required when temporal bone pathology is suspected to involve the intracranial compartment.

#### **15.4.1 Computed Tomography**

#### **<IP_ADDRESS> Temporal Bone CT Technique**

Dual acquisition temporal bone CT (separately acquired direct axial and direct coronal images) has largely been replaced with multidetector row CT (MDCT) in which a single set/volume of axial images are acquired and reformatted in multiple planes. Thoughtfully performed MDCT 195

reduces radiation dose, and its rapid acquisition minimizes artifact from patient motion. Intravenous contrast is typically not used with temporal bone CT because when contrast is necessary (tumors, vascular pathology such as dural fistulas), then higher resolution MRI, MRI with MRA, or CTA are usually obtained.

For temporal bone CT the patient is placed supine in the gantry with the head angled superiorly and posteriorly. The neck is hyperextended so that the orbits are canted out of the pathway of the X-ray beam to minimize exposure to the lens. Gantry tilt may need to be avoided to facilitate image reconstruction and reformats. Scan coverage is from the roof of the temporal bone (the arcuate eminence) through the mastoid tip. Thin collimation to achieve high resolution is extremely important as the anatomy of the temporal bone involves very small structures. A collimation of 0.6–1.0 mm provides appropriate resolution. The raw data from each ear is most often reconstructed into 0.6–0.75 mm thin axial images in bone algorithm at a DFOV of 100 mm that effectively magnifies the images. Technologists provide reconstructed images including 0.6–1.0 mm reformats in the axial plane parallel to the lateral semicircular canal created from a sagittal plane, and 0.6–1.0 mm reformats in the coronal plane. Axial images with 2–3 mm section thickness of the entire scan volume are also provided in soft tissue algorithm.

Reformats may be obtained in sagittal or oblique planes to improve the detection of pathology in specific clinical settings such as superior semicircular canal dehiscence.

Stenver reformat: On the console the technologist scrolls through the sagittal plane until a view of the lateral semicircular canal is obtained. A reformatted axial plane parallel to the lateral semicircular canal is made. The technologist then scrolls through this axial data set and Stenver reformats are made by tracing a line perpendicular to the long axis of the summit of the superior semicircular canal at submillimetric intervals. This plane is perpendicular to the roof of the superior semicircular canal displaying it in cross section.

Poschl reformat: On the console the technologist scrolls through the sagittal plane until a view of the lateral semicircular canal is obtained. A reformatted axial plane parallel to the lateral semicircular canal is made. The technologist then scrolls through this axial data set and Poschl reformats are made by tracing a line parallel to the long axis of the summit of the superior semicircular canal at submillimetric intervals.

#### **15.4.2 Magnetic Resonance Imaging**

MRI of the temporal bones is performed in a head coil and should include thin section unenhanced and enhanced axial T1-weighted images, and enhanced coronal T1-weighted images. Fat suppression in at least one enhanced plane should be performed to distinguish fat from enhancement, especially in the region of the petrous apex. A maximum section thickness of 3 mm with no interslice gap and a small FOV are required to provide images able to depict the fine detail of the anatomy and pathology in the temporal bone. Thin section (1 mm or submillimetric), 3D T2-weighted techniques are valuable in temporal bone imaging to evaluate the relationship of pathologic processes such as a vestibular schwannoma with the surrounding nerves, the patency of labyrinthine structures, the size of the endolymphatic duct and sac, and the extent of cochlear dysplasia in congenital or developmental hearing loss. Reformatted oblique sagittal images perpendicular to the long axis of the internal auditory canal are helpful in identifying cranial nerve hypoplasia or aplasia. Diffusion-weighted imaging (DWI) can help in distinguishing cholesteatoma which typically have restricted diffusion from inflammatory middle ear cavity opacification which has facilitated diffusion.

Axial T2-weighted, flair, and enhanced T1-weighted images of the brain should be performed to assess for intracranial extension of temporal bone pathology, and also to exclude central nervous system pathology that might produce tinnitus, vertigo, hearing loss, or cranial nerve symptoms such as demyelinating disease, stroke, or inflammation/ infection.

#### **15.5 Tinnitus and Hearing Loss without a Mass**

When no mass is seen on imaging, the radiologist should closely review the inner ear structures. The common causes of tinnitus and hearing loss without a mass include otospongiosis, labyrinthitis ossificans, superior semicircular canal dehiscence, and enlarged vestibular aqueduct syndrome.

#### **15.5.1 Otospongiosis**

Otospongiosis is an idiopathic progressive disease of pathological bone remodeling that causes conductive, sensorineural, or mixed hearing loss. It results in spongiosis or sclerosis of portions of the petrous bone. Conductive hearing loss is usually secondary to abnormal bone encroaching on stapes with impingement on the stapes footplate. Therefore, stapes surgery is the traditional initial treatment for otosclerosis, but is being augmented or replaced by innovations in hearing aid technology and cochlear implants.

Symptoms typically start in the second or third decade of life and presentation is with progressive conductive hearing loss (80% bilateral) with a normal tympanic membrane, and no evidence of middle ear inflammation. On otoscopic exam-

**Fig. 15.1** Fenestral otospongiosis on the left with signs of lucency in the fissula ante fenestram (arrow)

ination, the promontory may have a faint pink tinge reflecting the vascularity of the lesion, referred to as the Schwartze sign.

On imaging, the disease is seen as lucency in the otic capsule. The most common location of involvement of otosclerosis is the bone just anterior to the oval window at a small cleft known as the fissula ante fenestram (*fenestral otosclerosis*) (Fig. 15.1). Involvement of the otic capsule separable from the oval window is referred to as "retrofenestral otosclerosis" or "cochlear otosclerosis" and can give a sensorineural component to the hearing loss.

A later presumably less active phase can occur where the bone becomes more dense and sclerotic. The bone still appears to encroach on the footplate but has a density closer to that of the otic capsule and thus may be difficult to identify.

#### **15.5.2 Labyrinthitis Ossificans**

Labyrinthitis ossificans is the late stage of labyrinthitis, in which there is pathologic ossification of spaces within the membranous labyrinth. Profound bilateral hearing loss from labyrinthitis ossificans is most commonly due to bacterial meningitis with onset of symptoms 3–4 months after the episode [2]. Other causes include trauma, hemorrhage, autoimmune disease, vascular obstruction of labyrinthine artery, and surgical insult.

Imaging can detect the evolution of labyrinthitis in three stages: acute, fibrous, and ossification. In the acute stage, enhancement of the inner ear is noted on MR images, but the CT scan may appear normal. In the intermediate fibrous stage of labyrinthitis, there is loss of fluid signal intensity on heavily T2-weighted sequence images (Fig. 15.2), while the

**Fig. 15.2** Labyrinthitis ossificans on the right with loss of fluid signal intensity on heavily T2-weighted sequence images

CT scan may still appear normal. In the late ossific stage, one sees replacement of the normal cochlea, vestibule, and/or semicircular canals by bone attenuation on CT scans.

#### **15.5.3 Superior Semicircular Canal Dehiscence**