Neuroimaging in Inflammatoryand Infectious Diseasesof the Spinal Cord

Philippe Demaerel and Sarah Cappelle

ContentsDefinition and Clinical Highlights . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Imaging Technique and Recommended Protocol for Inflammatory/InfectiousDiseases of the Spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Indications for Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Clinical Entities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Multiple Sclerosis (MS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Infectious and Postinfectious Myelitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Neuromyelitis Optica Spectrum Disorder (NMOSD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Granulomatous Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Systemic Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Toxic and Treatment-Related Myelopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Meningoradiculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Intraspinal Abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Interpretation Checklist and Structured Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Sample Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Case 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Case 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

AbstractProgress in knowledge on inflammation andinfection of the spinal cord has led to a moreimportant role of radiology in the diagnosticwork-up of these diseases.

MR imaging is the only radiological tech-nique that allows a direct visualization of thespinal cord, and multisequence imaging is veryimportant for the adequate detection and local-ization of pathology.

In clinical neuroradiology, MR imagingis extremely helpful in differentiating multiplesclerosis from neuromyelitis optica spectrumdisorders (NMOSD) with longitudinally exten-sive myelitis and in suggesting the diagnosis in

P. Demaerel (*) · S. CappelleDepartment of Radiology, University HospitalsKU Leuven, Leuven, Belgiume-mail: philippe.demaerel@uzleuven.be; sarah.cappelle@uzleuven.be

# Springer Nature Switzerland AG 2018F. Barkhof et al. (eds.), Clinical Neuroradiology,https://doi.org/10.1007/978-3-319-61423-6_40-1

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granulomatous, autoimmune, and infectiousdiseases, partly based on their gadolinium-enhancement pattern.

The clinical history, serology, and CSFanalysis should be available when investigat-ing a suspected spinal cord inflammation orinfection and, in some cases, brain MR imag-ing will be required to confirm or exclude aspecific disease.

KeywordsAutoimmune · Meningoradiculitis · Myelitis ·Myelopathy · Neuromyelitis optica

List of AbbreviationsAb AntibodyACE Angiotensin converting enzymeADEM Acute disseminating

encephalomyelitisAQP4 Aquaporin 4CSF Cerebrospinal fluidDIR Double inversion recoveryLETM Longitudinal extensive transverse

myelitisMR Magnetic resonanceMOG Myelin oligodendrocyte

glycoproteinMS Multiple sclerosisNMOSD Neuromyelitis optic spectrum

disordersPCR Polymerase chain reactionSLE Systemic lupus erythematosusSS Sjögren syndromeSTIR Short tau inversion recovery

Definition and Clinical Highlights

Acute and subacute transverse myelopathy canbe of inflammatory, demyelinating/autoimmune,infectious, metabolic, toxic, (para)neoplastic, andvascular origin (see also chapter “▶Tumoral andVascular Disorders of the Spine and SpinalCord”).

Acute transverse myelitis has been defined asa spinal cord dysfunction of the ascending anddescending pathways with symptoms reaching amaximum intensity within 4 h up to 21 days after

onset. The patient develops sensory, motor, orautonomic dysfunction on both sides, alwayswith a sensory level. Cord compression by ex-tramedullary causes should be excluded. CSFpleocytosis and elevated immunoglobulinand/or pathological gadolinium enhancementshould be present.

The clinical presentation is different betweenacute complete transverse myelitis and acute par-tial transverse myelitis. From the imaging point ofview, an acute complete transverse myelitis oftenpresents with a longitudinal extensive transversemyelitis (LETM, extending over three to fourvertebral segments) while acute partial transversemyelitis is often characterized by lesions with anextension of less than two vertebral bodies. Thelatter is typically seen in multiple sclerosis (MS).

Inflammatory/infectious and demyelinatingspinal cord pathology usually presents asmyelitis and/or (meningo)radiculitis. MS andneuromyelitis optica spectrum disorders(NMOSD) are the most common demyelinatingdiseases. Other possible causes of myelitis aresystemic lupus erythematosus, Sjögren syndrome(SS), and postinfectious etiologies includingADEM. In 15–30% of the patients, no underlyingcause can be found despite extensive search andthe myelopathy is classified as idiopathic.

Clinical information, serological findings,and CSF analysis are essential in guiding theradiologist in the interpretation of the imagingexaminations.

The typical pathological findings in transversemyelitis consist of collections of lymphocytesand monocytes with a variable degree of demye-lination, axonal injury, and microglial activation.

Imaging Techniqueand Recommended Protocolfor Inflammatory/InfectiousDiseases of the Spinal Cord

MR imaging is the modality of choice in thediagnostic work-up and plays a crucial rolein excluding compressive disorders or spinalcord ischemia and in narrowing the diagnosis ina patient with suspected myelitis. The protocol

2 P. Demaerel and S. Cappelle

should include sagittal and axial T2-weightedimages as well as pre- and post-gadoliniumT1-weighted images. When MS is suspected, atleast two different T2-weighted sequences arerecommended (e.g., T2 and short-tau inversionrecovery (STIR), proton density/T2 and STIR orT2 and DIR) and the spatial resolution should beat least 3� 1� 1mm3. The optimal first echo timeof the dual-echo T2-weighted sequence should beselected in order to obtain an identical signal in theCSF and in the normal spinal cord (Fig. 1). TheSTIR sequences are characterized by a bettercontrast-to-noise ratio but are prone to flow-related artifacts. Axial two-dimensional gradient-echo sequences are recommended for localizingMS plaques in the spinal cord because of therelatively short acquisition time and the absenceof flow-related artifacts.

Diffusion tensor imaging has been shown toprovide additional information on degree ofdemyelination (decreased fractional anisotropy)or axonal injury (increased mean diffusivity) butis not routinely used in daily clinical practice.

Indications for Imaging

MR imaging is indicated whenever there is aclinical suspicion of spinal cord compression orspinal cord involvement.

Clinical Entities

Multiple Sclerosis (MS)

MS is a multiphasic disease and most patientspresent in the second or third decade of life.

Further understanding of the pathophysiologyof MS remains extremely important and correla-tion of pathology with imaging findings may leadto advances in monitoring and treatment ofpatients.

Perivenular inflammation can be observed inMS by using post-gadolinium imaging andT2-weighted magnitude and phase imaging.Inflammation can be associated with subacutepial demyelination and subsequent atrophy. A

higher microglial activation and a reduced myelinwater fraction has been reported in normalappearing white matter. The reduced myelinwater fraction was also seen in MS plaques inthe spinal cord and a progressive decrease hasbeen observed over several years. A decreasedintracellular volume fraction and neurite densitytogether with an increased dispersion index andisotropic volume fraction may reflect loss of fibercoherence and increased extracellular volume inbrain and spinal cord MS lesions. We refer to thechapter “▶Brain Demyelination” for a moreextensive description of the role of MR imagingin the pathophysiology of MS.

Myelin oligodendrocyte glycoprotein (MOG)antibodies (Ab) are a marker of demyelination.Anti-MOG antibodies have been demonstratedin the early stages ofMS and frequently in patientswith acute disseminating encephalomyelitis(ADEM) or with a clinically isolated syndrome,but can also occur in isolation (part of NMOSD).

Transverse myelitis is an uncommon initialpresentation but can be seen at some stage in upto 90% of the patients with MS. The clinicalpresentation often is an acute partial transversemyelitis. In a minority of the patients (<10%),spinal cord lesions can be seen in the absence ofcerebral lesions and 20–30% of these patients willconvert in MS.

The presence of oligoclonal bands in the CSFis often seen in MS while it is absent in NMOSD.

In a patient presenting with a nonspinal clini-cally isolated syndrome and with brain imagingfindings not fulfilling the criteria of dissemina-tion in space, whole spinal cord MR imaging isindicated because the demonstration of one lesionis associated with an increased risk of developingclinically definite MS. Spinal cord MR imaginghas a role in meeting the dissemination in spacecriteria. Demonstration of dissemination in time ismore difficult because of the less reliable de-tection of new spinal cord plaques and the diffi-culty of detecting contrast enhancement in spinalcord plaques. New silent spinal cord lesions areextremely rare.

Indications for spinal cord imaging in MSare: (1) clinically isolated syndrome and normalor nonspecific brain abnormalities, (2) partial

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 3

Fig. 1 (a–g) Multiple sclerosis. Sagittal T2-weightedimage demonstrates the typical sagittal “perivenular” ori-entation of a plaque at level C2 (a). Sagittal spin-echo

proton density (b) and T2-weighted (c) and turbo spin-echo T2-weighted (d) images in another patient showseveral plaques in the cervical spinal cord (arrows). Note

4 P. Demaerel and S. Cappelle

myelitis in order to exclude nondemyelinatingpathology, and (3) transition to a progressivephase of MS.

The following MR features can be used tocharacterize spinal cord lesions in relapsing remit-ting MS (Fig. 1):

– Usually more than one short-segment lesions(about the length of a vertebral body on sagittalimage and involving less than half the spinalcord on axial images).

– Most plaques are located in the cervical spinalcord and often affect the pyramidal andspinothalamic tract and/or the dorsal column sys-tem (Fig. 1). Gadolinium uptake may be seen inthe acute stage but is now considered to be arather insensitive marker of blood–brain barrierbreakthrough. After the acute stage, plaques tendto be well defined and oval in shape along thelong axis of the venous system (Fig. 1).

In primary progressive MS, diffuse abnormal-ities can be seen in the spinal cord.

In both primary and secondary progressiveMS, generalized cord atrophy occurs, which is astrong predictor of clinical disability.

A high number of spinal cord plaques andatrophy are two imaging findings associatedwith a worse clinical outcome. Quantitative MRimaging of the spinal cord has demonstratednovel associations with disability and diseaseprogression.

Infectious and Postinfectious Myelitis

Acute transverse myelitisis a monophasic diseasetypically presenting with rapidly progressingparaplegia, a sensory disturbance, and bowel/bladder disturbance. It often concerns a completetransverse myelitis (Fig. 2).

A variety of viral agents has been reported.Increased serological titer, increased CSF proteinand positive CSF PCR for viral genome can sup-port the diagnosis, but etiological diagnosis is notalways obtained and the myelitis is then classifiedas “idiopathic.”

HIV myelitis is relatively rare and tends toaffect more often the thoracic spinal cord. Thisoften occurs in association with HIV encephalitisand reflects the viral infection of the central ner-vous system. It is important to differentiate thisfrom HIV (vacuolar) myelopathy, a slowly pro-gressive disease with symmetrical high signal inthe dorsolateral parts of the thoracic spinal cord(Sartoretti-Schefer et al. 1997).

Up to 40% of pediatric transverse myelitiscases are preceded by an, often viral, infection(Alper et al. 2011) and most likely immune-mediated (i.e., ADEM). The risk of developingMS is very low. Postvaccination myelitis canoccur too. Most patients with ADEM haveextensive brain involvement. The thoracic spi-nal cord is preferentially involved but wholespinal cord involvement has been reported too.There is usually no gadolinium enhancement.Patients with ADEM and positive serum MOGAb have a better outcome and more often havespinal cord involvement with lesions extendingover more than three vertebral levels (LETM).MOG Abs are more frequently detected in youn-ger patients and more often in male thanaquaporin-4 (AQP4) Abs, which have a verystrong female preponderance.

The following MR features can be used tocharacterize spinal cord lesions in postinfectiousmyelitis (Fig. 2):

– Usually one lesion extending over three to fourvertebral segments (LETM) and involving morethan 2/3 of the cross-sectional area of the spinalcord at the cervical and/or thoracic level.

��

Fig. 1 (continued) the superiority of proton densityweighted image (b) in visualizing the plaques. AxialT2-weighted gradient-echo images (e, f) in another patientshow the typical location of MS plaques in the lateral (e)

and dorsal (f) white matter. Sagittal T2-weighted image (g)in another patient shows spinal cord lesions at level C2/C3and at level Th5

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 5

– Gadolinium enhancement can occur and ismore frequent in the subacute stage than inthe acute stage. A bright spotty enhancementis extremely rare.

The lack of contrast enhancement in someacute cases of myelitis could be explained by theacute onset of venous hypertension and sub-sequent reduced perfusion leading to ischemicchanges.

Parasitic myelitis is rare outside Africa, Asia,and South America. Schistosomiasis can occa-sionally be seen in Europe and usually in frequenttravelers. Schistosoma mansoni is the most impor-tant causative agent. It typically involves thelower thoracic spinal cord and conus terminaliswith patchy or nodular enhancement (Fig. 3).Blood and CSF serology can confirm the diagno-sis and eggs can be found in the patient’s stool.

Neuromyelitis Optica SpectrumDisorder (NMOSD)

Neuromyelitis optica (NMO, Devic’s disease) isa demyelinating/inflammatory disease withlesions at sites of high AQP4 expression: spinal

cord, optic nerve, circumventricular organs,brainstem, thalamus, and hypothalamus (seechapter “▶Neuromyelitis Optica Spectrum Dis-orders”). AQP4, the target antigen protein, is atransmembrane channel facilitating the movementof water across membranes and is microscopicallyexpressed in astrocyte foot processes. AQP4 Abgets access to the central nervous system throughareas of increased blood–brain barrier permeabil-ity and binds to the AQP4 channel. This bindingresults in channel malfunction with disturbance ofthe water homeostasis, activation of complementswith oligodendrocyte injury, and blood–brain bar-rier breakdown. When the spinal cord is involved,an acute complete transverse myelitis is muchmore frequent than an acute partial transversemyelitis. Neurological symptoms and physicaldisability is more severe in NMO than in MSand recovery is less good.

The major criteria for NMO include (1) (bilat-eral) optic neuritis mainly involving the posteriorpart of the optic nerve and the optic chiasm,(2) transverse myelitis extending over more thanthree vertebral segments (LETM), and (3) no evi-dence of sarcoidosis, vasculitis, SLE, Sjögrensyndrome. In addition, one of the followingshould also be present: (1) brain abnormalities

Fig. 2 (a–c) Epstein-Barr myelitis. Sagittal T2-weighted(a, b) and T1-weighted postcontrast (c) images. An LETMis seen in the cervical spinal cord extending from themedulla oblongata to level C5 (a). Follow-up 3 weeks

later shows progressive swelling of the spinal cord withpatchy areas of enhancement in a lesion, now extending tolevel C3. These rapidly changing extension do suggest amyelitis rather than a tumor

6 P. Demaerel and S. Cappelle

not fulfilling Barkhof criteria or (2) positive test inserum or CSF for AQP4 Ab.

Atypical forms of NMO have been reportedand subsequently the term NMOSD was intro-duced in 2007. NMOSD consists of (1) NMO,(2) limited/partial/inaugural form of NMO,(3) Asian optic-spinal myelitis, (4) optic neuritisor LETM associated with autoimmune disease,and (5) optic neuritis or myelitis with brain lesionstypical of NMO.

A distinction is made between AQP4 Ab+NMOSD and AQP4 Ab� NMOSD. In patientswith the NMOSD phenotype without AQP4 Ab,MOG Ab can be found in 10–15% of them. Itmore often concerns male patients with an overallbetter prognosis. Six clinical entities have beendefined, i.e., acute myelitis, optic neuritis, acutebrainstem syndrome, area postrema syndrome,acute diencephalic syndrome (with MR abnor-malities), and symptomatic cerebral syndrome(with typical MR lesions). The criteria for AQP4

Ab+ NMOSD require at least one clinical charac-teristic and the exclusion of alternative diagnoses.For AQP4 Ab� NMOSD, at least two clinicalcharacteristics are required, at least one of thembeing optic neuritis, LETM myelitis, or area post-rema syndrome, and dissemination in spaceshould be documented. In a single episode ofLETM, up to 40% of the patients have NMOSD,while in case of relapse this increases to 70%(Pittock and Lucchinetti 2015). AQP4 Ab isfound in 30–50% of all patients with LETM.The presence of AQP4-Ab and/or an LETM hasa worse functional prognosis and is associatedwith a higher risk of relapse (Iyer et al. 2014).

The indication for imaging is usually the oc-currence of acute spinal cord symptoms. Imagingplays an important role in NMOSDwithout AQP4Ab, because the diagnostic criteria require theconfirmation of the clinical entity onMR imaging.

The following features can be used to charac-terize spinal cord lesions in NMOSD (Fig. 4):

Fig. 3 (a–c) Neuroschistosomiasis. Sagittal T2-weighted(a), sagittal and axial T1-weighted postcontrast (b,c) images. An LETM is seen in the lower thoracic spinal

cord and conus terminalis (a). Scattered nodular clusters ofenhancement are seen at the surface of the spinal cord andthere is some evidence of meningeal enhancement (b, c)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 7

– Usually one central lesion extending over threeto four vertebral segments (LETM) and in-volving more than 2/3 of the cross-sectionalarea of the spinal cord at the cervical and/orthoracic level.

– A low T1 signal, reflecting extensive paren-chymal damage.

– A bright spotty T2 signal is seen in more than50% of the patients (Yonezu et al. 2014).

– Ring enhancement was observed in 1/3 ofthe patients and was considered useful inthe differential diagnosis of LETM (Zalewskiet al. 2017).

Patients with NMOSD are at high risk (approx.40%) of developing other autoimmune diseases(e.g., rheumatoid arthritis, SLE, antiphospholipidsyndrome) and this is more frequently seen in

AQP4 Ab+ patients (see “▶Systemic Autoim-mune Diseases”).

Spinal cord MR imaging is very helpful indifferentiating MS from NMOSD. The initialclinical presentation of NMOSD and clinicallyisolated syndrome in MS can be similar. AnLETM lesion is 98% sensitive and 83% specificfor differentiating NMO from MS. Conversely,finding multiple short-segment cord lesions isalmost pathognomonic for MS, though NMOcases with initially small lesions have beenreported. Differential diagnosis with MS is impor-tant because other treatment options are availablefor NMO, e.g., plasmapheresis and intravenousgammaglobulins and some MS drugs may aggra-vate NMO (e.g., fingolimod, natalizumab).

Currently, the characterization of LETM in theabsence of AQP4 Ab, a seronegative LETM, is amore difficult challenge. Spinal cord MR imaging

Fig. 4 (a–c) NMOSD. Sagittal and axial T2-weighted(a, b) and sagittal T1-weighted postcontrast (c) images.An LETM is seen extending from level Th1 to Th5 with

predominant gray matter involvement (a, b). On post-contrast images, a diffuse patchy enhancement is seen (c)

8 P. Demaerel and S. Cappelle

cannot differentiate between seronegative andAQP4 Ab+ LETM but brain MR imaging wasusually normal in seronegative LETM.

Granulomatous Diseases

Sarcoidosis, tuberculosis, brucellosis, and syph-ilis can present with meningoradiculitis ormyelitis.

Neurosarcoidosis can be observed as an iso-lated disease manifestation in the absence of sys-temic sarcoidosis in approximately 3%. In manycases, subsequent involvement of other body tis-sues follows.

The underlying pathophysiology of neurosar-coidosis remains under debate. The formation ofgranulomas is thought to represent the incompletedegradation of antigenic stimuli in individualswith a genetic predisposition and through addi-tional environmental triggers, resulting in a strongactivation of CD4+ lymphocytes which cause anamplification of the immune response with dif-ferentiation of macrophages into giant cells.Genetic mutations such as those involving thegenes encoding for annexin A11 protein andbutyrophilin-like 2 seem to play a role in thepathogenesis.

The clinical presentation is usually character-ized by a subacute onset of neurological signsindicating spinal cord pathology.

Central nervous system involvement occurs inapproximately 10% of patients with sarcoidosis.Primary involvement of the spinal cord is uncom-mon and more frequently concerns the cervicallevel and the cervicothoracic junction (Fig. 5).The spinal cord lesions are characterized by alongitudinal extensive high signal onT2-weighted images with subpial enhancementafter intravenous administration of Gadolinium.Occasionally, a central canal enhancement canbe observed giving rise to a “trident sign” onaxial images. Granulomatous infiltrates can beseen in the meninges, pituitary gland, hypothala-mus, and cranial nerves. Cerebrospinal fluidabnormalities are nonspecific and can evenremain normal in patients with spinal cordinvolvement only. Elevated serum and CSF

angiotensin-converting enzyme (ACE) can behelpful in reaching a diagnosis. FDG-PET isvery sensitive in detecting inflammatory activityin thoracic or mediastinal lymph nodes. It is usedto search lymph nodes that are suitable for biopsyand to monitor the disease following treatment.The treatment of neurosarcoidosis consists of glu-cocorticoids or, as a second-line therapy in case ofdisease severity or corticoid toxicity, immunosup-pressive therapies such as methotrexate, chloro-quine, azathioprine, or cyclophosphamide can beused as well as infliximab, a monoclonal Abagainst tumor necrosis factor-α. Complete remis-sion of active disease on MR imaging has beenreported in approximately 50% of the patients andpartial remission in 30%. Clinical improvementhas been observed in approximately 75% (com-plete recovery approximately 25% and partialrecovery 50%). Variable treatment outcomeshave been reported and it is important to notethat the central nervous system is more prone toirreversible injury and treatment response is dif-ferent from what can be observed in lung or skinlesions.

A corset-like neuropathy may raise the suspi-cion of neurosarcoidosis, especially if cranialnerve palsy is observed too. Leptomeningeal infil-trates along the spinal cord and cauda equina canbe observed. Four consecutive imaging stageshave been described (Junger et al. 1993):

1. Leptomeningeal enhancement2. Centripetal parenchymal extension with

swelling3. Less swelling with focal enhancement4. Normal spinal cord size without enhancement

The histopathological findings of neurosar-coidosis are less well known than those of sar-coidosis involving the lung or the lymph nodes.However, similar formation of epitheloid granu-lomas is seen although they are smaller and con-tain less giant cells. On imaging, one can seeeither small granules (miliary form) or larger con-glomerate of granulomas (nodular/tumoral form).The latter may look like a meningioma on imag-ing. Microscopically, the lesions are characterizedby 150–350 μm collections of epitheloid

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 9

histiocytes and lymphocytes surrounded by a rimof lymphoid cells. Older granulomas becomefibrotic and are non-necrotizing andnon-caseating in neurosarcoidosis.

Infectious granulomatous diseases such astuberculosis and brucellosis can yield similarimaging findings with either spinal cord involve-ment and/or meningoradiculitis (Fig. 6).

In neurosyphilis myelitis, the “candle gutteringsign” has been reported on postcontrast imagesand has been ascribed to the invasion of thespinal cord from its surface. The enhancingnodule is located centrally in the area of spinalcord edema (Fig. 7).

Systemic Autoimmune Diseases

Myelitis has been reported to occur occasionally(1–3%) in a large number of autoimmune disor-ders, e.g., systemic lupus erythematosus (SLE),

antiphospholipid syndrome, Sjögren’s syndrome,Behçet’s disease, mixed connective tissue disease,rheumatoid arthritis, ankylosing spondylitis.

The association with NMO has been reportedin more than 20 autoimmune diseases. The path-ogenesis is not fully clear and it is likely that thereare different possible theories. Myelitis could bedue to a coexistent NMO spectrum disorder or dueto a vasculitic process with inflammation andmyelomalacia. An underlying vasculitic processis associated with an acute onset and prognosisis less good than in patients presenting with coex-istent NMO. Imaging may reveal LETM as wellas multifocal small lesions with symmetrical graymatter involvement.

In SLE, spinal cord involvement is seen in lessthan 2% of the patients. The lesions can be focal orextensive with central location and usually withenhancement. Antiphospholipid antibodies oranticardiolipine antibodies can often be demon-strated. MR imaging can remain normal at

Fig. 5 (a–c) Neurosarcoidosis. Sagittal T2-weighted (a),sagittal and axial T1-weighted postcontrast (b, c) images.A hyperintense lesion with surrounding edema is seen in

the dorsal spinal cord extending from level C4 to Th1 (a).There is strong and homogeneous enhancement on thepostcontrast images (b, c)

10 P. Demaerel and S. Cappelle

presentation in up to 30% of the patients (Li et al.2014). In these patients, MR imaging should berepeated in the days after the first scan.

In SLE, differences have been observed be-tween myelitis with gray matter involvement andmyelitis with white matter involvement. Inpatients with gray matter involvement, spinalcord edema is seen in an LETM often withoutgadolinium enhancement. This corresponds to aclinical pattern of lower motor neuron signs, uri-nary retention, and a severe but monophasiccourse. In patients with white matter involvement,LETM is uncommon and gadolinium enhance-ment is seen more frequently. Clinically, uppermotor neuron signs are seen and these patientoften present with recurrent episodes.

Histopathology in SLE myelitis revealed peri-vascular lymphocytic infiltration, ischemia,necrosis, and vasculitis.

The treatment consists of intravenous cortico-steroids and cyclophosphamide.

The presence of lesions, their number, andextension might have an impact on the responseto treatment. There seems to be a relationshipbetween SLE and NMO, but it stills remainsunclear whether or not they represent two differ-ent clinical entities. Antinuclear Ab is positive in95% of the patients with SLE.

Sjögren syndrome (SS) can present withseveral different neurological manifestations.Spinal cord involvement can be observed in approx-imately 30% of the patients with SS and usuallyinvolves the cervical cord. In patients with spinalcord lesions, SS canmimicMS (primary SS) or evencoexist with MS or SLE (secondary SS) (Fig. 8).

Spinal cord involvement often does notrespond to steroids and intravenous cyclophos-phamide is indicated.

Fig. 6 (a–c) Neurotuberculosis. Sagittal T2-weighted (a), sagittal and axial T1-weighted postcontrast (b, c) images (c,arrow). A tuberculoma is seen in the thoracic spinal cord with surrounding edema

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 11

Patients with SS can present with a sensoryganglionopathy. The disease process in this entityis localized in the sensory neurons of the dorsalroot ganglia. The clinical presentation is charac-terized by loss of joint position and sensory ataxia.MR imaging shows symmetrical lesions in thedorsal columns of the spinal cord, representingdegeneration of the central sensory pathway andoften associated spinal cord atrophy can beobserved (Fig. 9) (Lauria et al. 2000). The MRfindings are similar in the acute and in the chronicstage. Nerve root conduction studies may notshow abnormalities early in the disease course.The treatment consists of rituximab and

intravenous immunoglobulin therapy and partialresolution of the lesions can be observed. Sensoryganglionopathies have also been described inother autoimmune diseases, in viral infectionsand genetic diseases.

Paraneoplastic myelopathy has been observedin association with lung and breast cancer and to alesser extent with gastrointestinal and hematolog-ical malignancies. Neuronal autoantibodies aredetected in the majority of patients. In a largeseries of patients with paraneoplastic myelopathy,MR imaging was normal in 1/3 of the cases. Inalmost half of the patients, a symmetrical highsignal with contrast enhancement was seen in the

Fig. 7 (a–c) Neurosyphilis. Sagittal and axialT2-weighted (a, b) and sagittal T1-weighted postcontrastimage (c). A central spinal cord lesion is seen at level

Th4–Th6 (a, b). On the postcontrast image, a centralstrongly enhancing “candle gutter” lesion is seen at theventral surface of the spinal cord (c, arrow)

12 P. Demaerel and S. Cappelle

white and gray matter (Fig. 10) (Flanagan et al.2011).

Toxic and Treatment-RelatedMyelopathy

Subacute combined degeneration can occur asa result of vitamin B12 deficiency or in the settingof nitrous oxide toxicity. Nitrous oxide is an anes-thetic agent but is also used as a recreational drug.Nitrous oxide inactivates B12 cobalamin. In thelatter, the myelopathy typically develops severalweeks after the drug exposure. The dorsal andlateral white matter of the lower cervical andthoracic spinal cord is typically affected (Fig. 11).

Radiation myelopathy/myelitis is a late com-plication, occurring after 2–3 months and up to10 years after radiotherapy. A high T2 signal isobserved in an edematous spinal cord, with areasof enhancement. Over time, the high signal disap-pears with atrophy of the spinal cord (Fig. 12).

Radiation myelopathy is dose dependent. Witha cumulative dose of 50 Gy, 0.2% of the patientmay develop radiation myelopathy, while thisincreases to 6% for 60 Gy and > 50% for 69 Gy(Kirkpatrick et al. 2010).

LETM can be seen on MR imaging in patientswith Crohn’s disease after the initiation of anti-tumour necrosis factor therapy (infliximab), withrapid improvement after discontinuation of thetreatment (Fig. 13).

Fig. 8 (a–c) Sjögren myelitis. Sagittal T2-weighted (a),sagittal and axial T1-weighted postcontrast (b, c) images.An LETM is seen extending from level Th2–Th7

(a, arrows). Patchy areas of contrast enhancement areseen predominantly in the white matter (b, c, arrows)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 13

Meningoradiculitis

Guillain-Barré syndrome is an acute immune-mediated process involving the peripheral ner-vous system. Several subtypes have beendescribed, including acute inflammatory demye-linating polyneuropathy, acute motor axonal neu-ropathy, Miller Fisher syndrome, and Bickerstaffbrainstem encephalitis. Acute inflammatory de-myelinating polyneuropathy typically presentswith an acute rapidly progressing symmetricalascending weakness and paralysis of the lowerlimbs with subsequent involvement of the upperlimbs and cranial nerves. The underlying path-ogenesis is most likely an autoimmune reactionagainst myelin in the peripheral nerves. Animmune response directed against the capsularantigens of Campylobacter jejuni producesantibodies that cross-react with myelin. Theseantiganglioside antibodies result in immunologi-cal damage. Leptomeningeal and/or nerve root

enhancement has been reported in Guillain-Barrésyndrome and typically involves the ventral nerveroots in the early days after admission (Fig. 14).Later dorsal nerve root enhancement is seentoo. Although pathology examination showsswollen nerves, there is usually no or mild thick-ening of the nerve roots of the cauda equina onMR imaging. Similar findings can be seen inMiller-Fisher syndrome, subacute/chronic inflam-matory demyelinating polyneuropathy, and hered-itary polyneuropathies.

Meningoradiculits along the cauda equina canbe seen in a large variety of infectious and inflam-matory diseases (Fig. 15). It is also important toemphasize the sometimes difficult differentialdiagnosis with meningeal carcinomatosis, leuke-mia, and lymphoma.

(Meningo)radiculitis can occasionally occurtogether with myelitis of the lower thoraciccord (conus terminalis) (Fig. 16). This hasbeen described as the Elsberg syndrome (Savoldi

Fig. 9 (a, b) Dorsal root ganglionopathy in Sjögren syndrome. Sagittal (a) and axial (b) T2-weighted images showcervical cord atrophy at level C4/C6 with symmetrical increased signal in the dorsal column

14 P. Demaerel and S. Cappelle

et al. 2017). This acute infectious syndromehas been ascribed to a reactivation of a Herpessimplex virus type 2 infection. Because of thepoor sensitivity of serologic examinations, criteriahave been proposed to support this diagnosisand the simultaneous demonstration of myelitis(centrally or ventrally) and radiculitis (ventraland/or dorsal nerve roots) on MR imaging is animportant finding.

Intraspinal Abscess

Infectious spondylodiscitis is frequent in elderlypeople and chronic diseases (renal insufficiency,cancer, and liver disease) are predisposing. Hema-togenous spread is the most common mechanism

but direct extension related to surgery and contig-uous spread from adjacent infectious organs isfrequently seen too. In bacterial/fungal spondylo-discitis, the vertebral bodies and discs are affected(see chapter “▶Degenerative and InflammatoryDiseases of the Spine”). Secondary involvementof the paraspinal soft tissue and involvement ofthe intraspinal epidural space can be observed(Fig. 17). The detection of an epidural abscesscan be difficult but is very important because ofthe high morbidity.

Most patients will present with acute neurolog-ical symptoms and infectious signs.

An intramedullary abscess is extremely rareand begins with a myelitis (Murphy et al. 1998).The spinal cord appears swollen and returns ahigh signal on T2-weighted images (Fig. 18).

Fig. 10 (a, b)Paraneoplasticmeningoradiculitis in apatient with aneuroendocrine tumor andpositive anti-Hu antibodies.Sagittal T2-weighted (a)and postcontrastT1-weighted (b) images.Increased signal is seen inthe spinal cord (a) withenhancement of the spinalcord and the cauda equina(b, arrows)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 15

Postcontrast images show a peripheral irregularenhancement. Spinal cord abscess can be seenafter surgery, trauma, and complicated meningitis.

Differential Diagnosis

In a patient presenting with symptoms of spinalcord dysfunction, a multidisciplinary approach isimportant for rapidly reaching a final diagnosis.The clinical history and clinical examinationtogether with laboratory investigations (serologyand CSF analysis) are crucial in order to assess the

MR imaging findings. Spinal cord MR imaging,either limited to a segment of the spinal cord orcovering the entire spinal cord/cauda equina, isthe best imaging modality to demonstrate pathol-ogy. Additional brain MR imaging can be useful,e.g., in suspected multiple sclerosis.

The exclusion of spinal cord compression isan emergency indication for MR imaging as it isthe only way to adequately localize the level ofpathology and refer a patient for urgent surgicalintervention or radiotherapy.

An acute onset of symptoms within minutes orhours should always raise the suspicion of spinal

Fig. 11 (a, b) Subacutecombined degeneration.Sagittal (a) and axial (b)T2-weighted images.Symmetrical lesions arenoted in the dorsal column(b, arrow)

16 P. Demaerel and S. Cappelle

cord ischemia or hemorrhage. Confirmation byMR imaging is possible by demonstrating lesionsin a typical vascular territory and by using specificsequences such as diffusion-weighted imaging(see chapter “▶Vascular Disorders of the Spineand Spinal Cord”). Enhancement after intrave-nous administration of Gadolinium is absent inthe acute stage but can be seen in the subacutestage which can then be confusing. One shouldalso consider the possibility of spinal cord ische-mia in the elderly patient presenting with a sub-acute onset of spinal cord dysfunction. CSFanalysis will often remain normal in thesepatients.

Acute myelitis is usually characterized bya subacute onset but can exceptionally present asan acute condition. In these patients, the lesionsare very often located in the cervical spinal cord

(which is much less common in ischemia) andCSF analysis will reveal increased protein andpleocytosis. Occasionally, the spinal cord swell-ing in myelitis can be indistinguishable from atumor (see chapter). The clinical history, CSFanalysis, and eventually rapid follow-up imagingwill usually solve this differential diagnosticproblem.

In a context of acute myelitis, CSF analysiswill be helpful in differentiating infection fromdemyelination. Oligoclonal bands are often pre-sent in multiple sclerosis and usually absent inviral or autoimmune myelitis. Viral DNA and/orAb can sometimes be detected in the CSF. Imag-ing plays an important role in differentiatingdemyelinating plaques from infectious myelitisor NMOSD (see this chapter).

Fig. 12 (a,b) Radiationmyelitis. SagittalT2-weighted (a,b) images.The vertebral metastasiswith spinal cordcompression is seen at levelTh4–Th5 (a). MR imaging5 months later shows anarea of high signal in thespinal cord extending fromlevel Th3–Th7 (b)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 17

In the appropriate clinical setting (inherited)metabolic diseases should be considered.

Interpretation Checklistand Structured Reporting

Depending on theneurological examination, MRimaging can be either limited to the cervical, tho-racic, or lumbar spine/spinal cord or encompassthe entire spine/spinal cord.

The following structure need to be reviewed onthe images:

– Spinal cord: Signal (T2/T1/T2*), size (swol-len/atrophy), location of lesion (gray and/orwhite matter), mass effect, extent of lesion,pattern, and degree of enhancement.

– Cauda equina: Assessment of thecal sac, size,and distribution of nerve roots, enhancementof nerve roots.

– Epidural space: Assessment of epiduralfat, check for epidural mass/spinal cordcompression.

– Spine: Bone marrow signal, vertebral bodymorphology, degree, and pattern ofenhancement.

– Soft tissue: Check ligaments and musclesalong the spine.

Sample Reports

Case 1

Patient history: A 4-year-old boy presentswith abdominal pain and difficulties in standingupright. He develops a progressive ataxic gait

Fig. 13 (a–d) Myelitis in a Crohn patient treatedwith vedolizumab. Sagittal T2-weighted (a, b), axialT2-weighted, (c) and sagittal postcontrast T1-weighted(d) images. An LETM is seen in the cervical and thoracic

spinal cord. Note the central location in the cord withoutinvolvement of gray and white matter (c) and the poorlydefined patchy enhancement (d)

18 P. Demaerel and S. Cappelle

over the past 2 days. On neurological examina-tion, there are meningeal signs and there is a mildfacial weakness.

Clinical diagnosis: Differential diagnosis:cerebellitis, posterior fossa tumor, ADEM,Guillain-Barré syndrome.

Purpose of MR study: Clarify the possibleposterior fossa tumor seen on brain CT, confirmor exclude other possible clinical diagnoses.

Imaging technique: Brain: axial T2 (A), sag-ittal FLAIR (B). Spinal cord: sagittal and axial T2(C,D), sagittal T1 precontrast (E), Sagittal andaxial T1 postcontrast (F,G).

Contrast agent and dose: 0.2 ml/kg macro-cyclic Gadolinium agent (0.1 mmol/kg).

Full findings: Brain MR imaging showsa large cisterna magna without evidence of a pos-terior fossa tumor (A,B). Spine MR imagingshows a dilated central canal without evidence ofa syringomyelia (C,D). Following the intravenousadministration of gadolinium, there is an intenseenhancement of the ventral nerve roots of thecauda equina (F,G).

Interpretation: The imaging findings in theposterior fossa represent a normal anatomical var-iant. There is no mass effect. The dilated centralcan be differentiated from a syringomyelia on the

Fig. 14 (a, b) Guillain-Barré syndrome. Sagittal (a) and axial (b) T1 weighted postcontrast images. Strong enhancementis seen along the ventral nerve roots of the cauda equina (a, arrow)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 19

basis of the anteroposterior size (< 3 mm) and thelocation within the spinal cord. The nerve rootenhancement represents meningoradiculitis andthe preferential involvement of the ventral nerveroots suggests a Guillain Barré syndrome.

Comment: The present case illustrates the roleof MR imaging in this difficult clinical differentialdiagnosis. It is important to know and to recognizenormal variants (large cisterna magna, dilatedcentral canal). The pattern of enhancement allowsthe very specific diagnosis of Guillain Barrésyndrome.

CSF analysis only showed a mild elevation ofprotein.

The diagnosis was confirmed by demonstrat-ing an acute demyelinating inflammatory poly-neuropathy on electromyography.

Treatment with intravenous immunoglobulinwas administered.

Case 2

Patient history: A 28-year-oldwoman presentswith general fatigue, memory loss, and episodes

Fig. 15 (a–c) Neuroborreliosis. Sagittal T1-weightedpre- (a) and sagittal (b) and axial (c) postcontrast images.Note the moderate enhancement of the cauda equina which

is best evaluated by comparing pre- and postcontrastimages side by side. On axial images, there is enhancementof both ventral and dorsal nerve roots (c)

20 P. Demaerel and S. Cappelle

of confusion. She experienced one short episodeof right-sided facial nerve palsy. There is no fever.She reported a common cold 1 month beforeadmission.

Clinical diagnosis: No possible diagnosisbased on the clinical presentation and neurologi-cal examination. A lumbar puncture did not revealany significant abnormality.

Purpose of MR study: Exclude cerebralabnormalities.

Imaging technique: Brain: axial FLAIR (A),T1 axial, sagittal, and coronal postcontrast (B–D).Spinal cord: sagittal T1 precontrast (E), T1 sagit-tal and axial postcontrast (F,G).

Contrast agent and dose: 0.2 ml/kg macrocy-clic Gadolinium agent (0.1 mmol/kg).

Full findings: A focal enhancing lesion is seenin the genu of the internal capsule and thalamus(A,B). Meningeal enhancement is seen along the

optic chiasm (C,D) and several nodules are seenalong the cervical spinal cord (D).

Note the spontaneous hyperintense appearanceof the filum terminale, representing a lipoma,without pathological significance (E). Followingintravenous administration of gadolinium, severalenhancing nodules are seen along the conusterminalis (F,G).

Interpretation:Based on the brainMR imagingfindings, there was a suspicion of leptomeningealmetastases. Primary tumors were considered, e.g.,germinoma, ependymoma, and pineoblastoma, butcould be excluded on MR imaging. A PET-CTwasperformed, demonstrating several hypermetaboliciliac, retromandibular, hilar, and inguinal glandspreferentially corresponding to lymphoma.

A biopsy of a lymph node in the neck revealedgranulomatous lymphadenitis compatible withneurosarcoidosis.

Fig. 16 (a–c) Elsberg syndrome. Sagittal T2-weighted(a), sagittal (b) and axial (c) T1-weighted postcontrastimages. An area of high signal is seen in the conus

terminalis (a). On postcontrast images, there is enhance-ment in the conus terminalis (black arrow) as well as alongthe nerve roots of the cauda equina (white arrows) (b, c)

Neuroimaging in Inflammatory and Infectious Diseases of the Spinal Cord 21

Fig. 17 (a–c) Epidural abscess. Sagittal T2-weighted (a),sagittal (b) and axial (c) T1-weighted postcontrast images.An extensive anterior epidural abscess is seen extending

from level C1–C6 with spinal cord compression andedema. Note the small prevertebral abscess (b, arrow)and the abscess in the neck muscles (c, arrow)

Fig. 18 (a–c) Bacterial myelitis. Sagittal T2-weighted (a),sagittal (b) and axial (c) T1-weighted postcontrast images.The entire spinal cord appears swollen and hyperintense

(a). There is a strong enhancement of the white matter (b, c,arrows)

22 P. Demaerel and S. Cappelle

Comment:MR imaging plays a crucial role inthe differential diagnosis of leptomeningealenhancement.

In a young adult with leptomeningeal dissem-inated brain and spinal cord lesions, metastasesshould always be considered but one should alsoconsider the possibility of granulomatous andinflammatory diseases.

One should always obtain pre contrast imagesof the spinal cord in order to avoid misinterpreta-tion of a lipoma of the filum terminale.

References

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Further Reading

The transverse myelitis consortium working groupmembers. Proposed diagnostic criteria and nosol-ogy of acute transverse myelitis. Neurology.2002;59:499–505.

Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria forthe diagnosis of multiple sclerosis: MAGNIMS con-sensus guidelines. Lancet Neurol. 2016;15:292–303.

Kearney H, Miller DH, Ciccarelli O. Spinal cord MRI inmultiple sclerosis – diagnostic, prognostic and clinicalvalue. Nat Rev. Neurol. 2015;11:327–38.

Rossi A. Pediatric spinal infection and inflammation. Neu-roimaging Clin N Am. 2015;25:173–91.

Wingerchuk DM, Banwell B, Bennett JL. Internationalconsensus diagnostic criteria for neuromyelitis opticaspectrum disorders. Neurology. 2015;85:177–89.

DeSanto J, Ross JS. Spine infection/inflammation. RadiolClin N Am. 2011;49:105–27.

Mirbagheri S, Eckart Sorte D, Zamora CA, Mossa-Basha-M, Newsome SD, Izbudak I. Evaluation and manage-ment of longitudinally extensive transverse myelitis:a guide for radiologists. Clin Radiol. 2016;71:960–71.

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