Imaging of Central Nervous System Autoimmune, Paraneoplastic, and Neuro-Rheumatologic Disorders

Imaging of Central REVIEW ARTICLE

Nervous System C O N T I N U UM A U D I O
I NT E R V I E W A V A I L AB L E
ONLINE
Autoimmune,
Paraneoplastic, and
Neuro-rheumatologic
Disorders
By Lama Abdel Wahed, MD; Tracey A. Cho, MD, FAAN
CITE AS:
CONTINUUM (MINNEAP MINN)
ABSTRACT
2023;29(1 , N E U R O I M A G I N G ) :
OBJECTIVE: This article provides an overview of the imaging modalities used 2 5 5 –2 9 1 .
in the evaluation of central nervous system (CNS) autoimmune,
paraneoplastic, and neuro-rheumatologic disorders. An approach is Address correspondence to
Dr Tracey A. Cho, Department of
outlined for interpreting imaging findings in this context, synthesizing a Neurology, University of Iowa
differential diagnosis based on certain imaging patterns, and choosing Hospitals and Clinics, 200
further imaging for specific diseases. Hawkins Dr, Iowa City, IA 52242,
tracey-cho@uiowa.edu.
LATEST DEVELOPMENTS: The rapid discovery of new neuronal and glial RELATIONSHIP DISCLOSURE:
Dr Abdel Wahed has received
autoantibodies has revolutionized the autoimmune neurology field and has
personal compensation in the
elucidated imaging patterns characteristic of certain antibody-associated range of $0 to $499 for serving
diseases. Many CNS inflammatory diseases, however, lack a definitive as a resident honorary speaker
with the Iowa Neurological
biomarker. Clinicians should recognize neuroimaging patterns suggestive Association and as an author for
of inflammatory disorders, as well as the limitations of imaging. CT, MRI, MedLink, LLC. Dr Cho has
and positron emission tomography (PET) modalities all play a role in received personal
compensation in the range of
diagnosing autoimmune, paraneoplastic, and neuro-rheumatologic $500 to $4999 for serving as a
disorders. Additional imaging modalities such as conventional angiography consultant for Horizon
and ultrasonography can be helpful for further evaluation in select Therapeutics plc and on a data
safety monitoring board for the
situations. Continued on page 291
ESSENTIAL POINTS: Knowledge of imaging modalities, both structural and

functional, is critical in identifying CNS inflammatory diseases quickly and UNLABELED USE OF
PRODUCTS/INVESTIGATIONAL
can help avoid invasive testing such as brain biopsy in certain clinical USE DISCLOSURE:
scenarios. Recognizing imaging patterns suggestive of CNS inflammatory Drs Abdel Wahed and Cho
diseases can also facilitate the early initiation of appropriate treatments to discuss the unlabeled use of
corticosteroids for the
diminish morbidity and future disability. treatment of autoimmune
neurologic diseases that have
no US Food and Drug
Administration–approved
medications.
© 2023 American Academy

of Neurology.
CONTINUUMJOURNAL.COM 255
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

IMAGING OF CNS AUTOIMMUNE, PARANEOPLASTIC, AND NEURO-RHEUMATOLOGIC DISORDERS
INTRODUCTION
C
entral nervous system (CNS) autoimmune, paraneoplastic, and
neuro-rheumatologic disorders, which are referred to as
neuroinflammatory diseases in this article, are a heterogeneous group
of pathologies that often require extensive testing, complex
decision-making, and multidisciplinary care. With the rapidly
increasing discovery of neuronal, synaptic, and onconeural autoantibodies, along
with more targeted and effective immune-based therapies, recognizing clinical
and radiographic patterns of neuroinflammatory diseases is critical for timely
diagnosis and initiation of treatment. Certain clinical features can be quite useful
in recognizing specific diseases, such as the orofacial dyskinesias in N-methyl-D-
aspartate (NMDA) receptor encephalitis or the pathognomonic faciobrachial
dystonic seizures seen in leucine-rich glioma inactivated 1 (LGI1) antibody
FIGURE 10-1
Autoimmune and inflammatory central nervous system (CNS) disorders and radiographic
differential diagnoses based on typical location.
ADEM = acute disseminated encephalomyelitis; AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid receptor; ANCA = antineutrophil cytoplasmic antibody; ANNA1 = antineuronal nuclear antibody type 1;
ANNA2 = antineuronal nuclear autoantibody type 2; AQP4 = aquaporin-4; CASPR2 = contactin-associated
proteinlike 2; CJD = Creutzfeldt-Jakob disease; CRMP5 = collapsin response mediator protein-5; CMV =
cytomegalovirus; DR2 = dopamine receptor 2; DPPX = dipeptidyl-peptidase–like protein 6; GABA A/B =
γ-aminobutyric acid type A or γ-aminobutyric acid type B; GABAR = γ-aminobutyric acid receptor; GAD65 =
glutamic acid decarboxylase 65; GFAP = glial fibrillary acidic protein; HHV6 = human herpes virus 6; HSV-1 =
herpes simplex virus type 1; IgG = immunoglobulin G; IgLON5 = immunoglobulin-like cell adhesion molecule 5;
KLH11 = kelch-like protein 11; LGI1 = leucine-rich glioma inactivated; mGLUR1 = metabotropic glutamate receptor
1; MOG = myelin oligodendrocyte glycoprotein; MS = multiple sclerosis; NMDAR = N-methyl-D-aspartate receptor;
PCA1 = Purkinje cell antibody 1; PML = progressive multifocal leukoencephalopathy; SCA = spinocerebellar ataxia;
SLE = systemic lupus erythematosus; VZV = varicella-zoster virus; WNV = West Nile virus.
256 FEBRUARY 2023

encephalitis. Others have specific biomarkers such as aquaporin-4 antibodies in KEY POINT
neuromyelitis optica spectrum disorder (NMOSD) or NMDA receptor antibodies
● Neuroimaging, especially
in NMDA receptor encephalitis. In many cases, however, definitive clinical MRI, can help identify the
patterns and laboratory assays are lacking or nonspecific. For instance, headache central nervous system
and altered mental status can occur with encephalitis, leptomeningitis, (CNS) compartments
pachymeningitis, or vasculitis. In such cases, neuroimaging is essential to help predominantly involved in
suspected autoimmune or
localize the syndrome and, thus, the differential diagnosis (FIGURE 10-1). In other
inflammatory disease:
cases, the neurologic syndrome is part of a systemic disease process, and imaging parenchymal, meningeal,
of non-neurologic sites can be helpful in identifying a systemic disease or an ventricular, or vascular.
extra-CNS target for biopsy.
As with any neurologic disease process, the approach to CNS inflammatory
diseases begins with identifying the tempo and progression of the process and the
localization within the CNS. The choice of imaging will vary depending on
whether the underlying disease is, for example, a chronic, relapsing spinal cord
process or a subacute meningeal process. The clinician must also understand how
imaging can help identify the core pathologic process in CNS inflammatory
diseases, including inflammation, edema, gliosis, and atrophy, and the
compartment within which the pathology predominates, whether parenchymal,
meningeal, ventricular, or vascular.1 When a systemic or paraneoplastic process is
suspected, imaging of additional sites may include the use of metabolic imaging
(positron emission tomography [PET]) or ultrasound, in addition to CT and MRI.
As with any biomarker, imaging findings must be interpreted in the context of
the time course and clinical localization of the patient’s symptoms. The
sensitivity and specificity of neuroimaging in neuroinflammatory disease vary
significantly. For instance, MRI in NMDA receptor encephalitis is frequently
normal or nonspecific throughout the course of the disease, whereas dorsal pial
enhancement of the spinal cord is particularly characteristic of active spinal cord
neurosarcoidosis. Understanding and accurately selecting the appropriate
neuroimaging modality are essential in evaluating any patient presenting with a
suspected inflammatory CNS disease.
CSF analysis provides crucial data to support the presence of a
neuroinflammatory process. Lumbar puncture should not be delayed in favor of
MRI in acute presentations with high clinical suspicion for bacterial meningitis.
In most other neuroinflammatory diseases when lumbar puncture is not
emergent, MRI is often acquired prior to lumbar puncture to better characterize
the disease process and guide CSF testing. In situations where MRI is delayed,
however, lumbar puncture should be pursued when suspicion is high. Despite
anecdotal concern for dural contrast enhancement as a result of lumbar
puncture, dural enhancement is rare after a single nontraumatic lumbar
puncture, especially if MRI is performed within 2 days.2,3 Another strategy to
limit traumatic lumbar puncture and a potentially confounding MRI contrast
pattern is using point-of-care ultrasound guidance, both for site-marking and
real-time guidance. This is especially important in patients who are obese (body
mass index above 35 kg/m2) with less palpable anatomic landmarks.4
CT IN NEUROINFLAMMATORY DISEASE
Head CT is a good first step to rule out large structural abnormalities such as
masses, hemorrhage, calcifications, bony abnormalities, or hydrocephalus;
however, its diagnostic value is limited by its poor resolution and suboptimal soft
tissue discrimination leading to lower sensitivity and specificity. Brain MRI is

almost always indicated to more thoroughly evaluate subtle findings. When MRI
is contraindicated or unavailable, head CT with contrast may be helpful in
identifying highly vascular or inflammatory lesions. CT is also particularly useful
when the disease process involves bone.
CT angiography provides excellent visualization of the integrity and caliber of
vessels based on the time elapsed from contrast administration: early for arterial
and delayed for venous phases. This noninvasive method is important in
evaluating large vessel obstructions, aneurysms and vascular malformations,
dissection, vasospasm, and vasculopathies such as CNS vasculitis (FIGURE 10-2).
Small and some medium vessel vasculitides may be missed on CT angiograms, so
clinicians must recognize the limitations of resolution when CNS vasculitis is
highly suspected.
MRI IN NEUROINFLAMMATORY DISEASE

The T2 fluid-attenuated inversion recovery (FLAIR) sequence is useful in
identifying sites of altered water content, including demyelination, edema,
inflammation, or gliosis; sagittal and coronal FLAIR may help visualize more
specific patterns of abnormality such as lesion orientation away from the
ventricular surface, or involvement of the corpus callosum. Some of these
pathologies are reversible, and the evolution of FLAIR signal change can help
elucidate the suspected pathologic process. High T2 contrast sequences such as
fast imaging employing steady state acquisition (FIESTA) or constructive
interference in steady state (CISS) highlight the contrast between CSF and other
structures such as blood vessels and cranial nerves in the basal cisterns and can
help identify lesions of these structures. Postcontrast T1 enhancement indicates
increased vascularity or blood-brain barrier disruption due to inflammation.
FIGURE 10-2
Axial CT angiography of the head demonstrating severe focal narrowing of the distal M1
segment of the left middle cerebral artery (A, arrow) and severe stenosis of the P2 segment
of the right posterior cerebral artery (B, arrow) in a patient with multifocal vasculopathy
(other areas not visualized here) secondary to immune checkpoint inhibitor vasculitis.
258 FEBRUARY 2023

High-resolution, thin-slice, three-dimensional sequences can be helpful in KEY POINTS
distinguishing extra-axial from intraparenchymal processes and provide better
● CT angiography provides
resolution of the brainstem and cranial nerve structures. High-resolution good anatomic resolution of
susceptibility-weighted imaging (SWI) can identify blood within structures such large and some medium-size
as venules, as well as sites of microhemorrhage. Diffusion-weighted imaging vessels but has poor
(DWI) can highlight acute infarcts as well as acute demyelination, abscess, and resolution for smaller
vessels.
some (generally high-grade) neoplasms.
● Leptomeningitis typically
POSITRON EMISSION TOMOGRAPHY IN NEUROINFLAMMATORY manifests as gyriform or
DISEASE serpentine enhancement
PET using fludeoxyglucose (FDG-PET) can visualize increased metabolic following the sulci.
activity in inflamed or hyperactive neuronal tissue (status epilepticus) or ● When assessing

decreased metabolism in damaged or dysfunctional tissue. The pattern of uptake extra-axial postcontrast
often relates to the stage and clinical manifestations of encephalitis, with earlier T1-hyperintense lesions, it is
stages associated with hypermetabolism and later stages with hypometabolism.5,6 important to review in the
context of other sequences
PET may be useful in cases of suspected autoimmune encephalitis when MRI is including T1 precontrast,
negative; however, noninflammatory status epilepticus, postictal states, and fluid-attenuated inversion
neurodegenerative diseases may also show similar patterns of hypermetabolism recovery (FLAIR), and
or hypometabolism. susceptibility-weighted
imaging (SWI).
SYNDROMIC APPROACH TO IMAGING ● Trauma or neurosurgery

As discussed previously, identifying the predominant compartment affected by may lead to meningeal
inflammation can help narrow the differential substantially. This section enhancement in the short
discusses imaging findings in specific syndromes of the CNS. term.
● Neurosarcoidosis should
Leptomeningitis be suspected in patients
Leptomeningitis is defined as inflammation of the CSF in the subarachnoid space with subacute onset of
(arachnoid and pia mater) and typically manifests as gyriform or serpentine multiple cranial
neuropathies with basal
enhancement following the sulci on postcontrast CT or MRI T1-weighted meningitis on MRI.
sequences (FIGURE 10-3). Sulcal enhancement can be hard to differentiate from
the normal appearance of vessels tracking along the sulci, so it is important to
evaluate images in different planes (ie, axial, sagittal, and coronal). Care should
also be taken to ensure that T1-hyperintense signal is not present on precontrast
images (and, thus, not truly enhancing on postcontrast images), as can be seen
with methemoglobin (subacute hemorrhage), fatty or highly proteinaceous
lesions (laminar necrosis), or melanin (metastatic melanoma). FLAIR can show
nonsuppression of CSF signal in the sulci manifested by hypertense signal
tracking along the sulci. SWI can help distinguish gadolinium enhancement of
the meninges from subtle subdural or subarachnoid hemorrhage and
calcifications.7 Clinical history should also focus on any prior traumatic events or
neurosurgical procedures, in which the breakdown of the blood-brain barrier can
lead to meningeal enhancement in the short term.
Most causes of acute meningitis are viral and bacterial, whereas subacute and
chronic meningitis have a much wider range of differential diagnoses that
includes systemic autoimmune diseases such as sarcoidosis and rheumatologic
diseases, including rheumatoid arthritis.8,9 Sarcoidosis is a multisystem
granulomatous inflammatory disorder. Neurologic involvement most commonly
presents as cranial neuropathies in up to 75% of patients with adjacent
leptomeningeal enhancement10 and as subacute to chronic meningitis syndrome
in up to 40%. In a study of MRI in 100 patients with neurosarcoidosis, 47%

FIGURE 10-3
Axial brain MRI of a patient with autoimmune meningoencephalitis. A, Postcontrast
T1-weighted MRI showing diffuse leptomeningeal enhancement (arrows). B, T2
fluid-attenuated inversion recovery (FLAIR) sequence from the same patient with
nonsuppression of the CSF signal; note the hyperintensities tracking along the sulci (arrows).
showed leptomeningeal enhancement with approximately one-quarter of those

patients demonstrating a basal localization (FIGURE 10-4).11 CNS involvement in
rheumatoid arthritis is extremely rare but can manifest as aseptic meningitis with
corresponding MRI changes.12 Rheumatoid meningitis can happen at any time in
the course of rheumatoid arthritis.13 Extension of leptomeningitis into the spinal
column may indicate infectious etiologies, such as herpesviruses, tuberculosis,
and syphilis among others,14 but can also be seen in inflammatory diseases such
as neurosarcoidosis.
Pachymeningitis
Pachymeningitis refers to inflammation of the dura mater. On MRI, postcontrast
T1 images show enhancement of the dura, with or without involvement of the
underlying leptomeninges (FIGURE 10-5). The pattern of enhancement may be
diffuse or focal, and smooth or nodular. Processes that can mimic inflammatory
pachymeningitis include intracranial hypotension, meningioma, and
postoperative reactive granulation tissue. Intracranial hypotension, whether
spontaneous or traumatic (caused by lumbar puncture, trauma, or
neurosurgery), usually manifests clinically with positional headache that is
exacerbated in upright positions and radiographically with diffuse and smooth
dural enhancement. Other imaging clues include a full sella, crowded pons, and
low-lying cerebellar tonsils.15 Intralesional calcifications and surrounding
hyperostosis or bony destruction may be helpful clues to distinguishing
meningiomas from inflammatory diseases.7 Trauma or neurosurgical procedures
may lead to chronic granulation tissue and neovascularity causing dural
enhancement for years after the procedure.7 Cranial neuropathies, both clinical
and radiographic, are a common feature of skull base pachymeningitis; dural
260 FEBRUARY 2023

KEY POINTS
● Meningioma is often
associated with intralesional
calcifications and
surrounding hyperostosis or
bony destruction, which
helps distinguish it from
focal pachymeningitis.
● Cranial neuropathies,
both clinical and
radiographic, are a common
feature of skull base
meningitis.
FIGURE 10-4
Axial (A) and coronal (B) postcontrast T1-weighted MRI showing nodular leptomeningeal
enhancement (A, B, arrows) most prominently affecting the basal cisterns in a patient with
probable neurosarcoidosis (lymph node biopsy positive).
thickening can lead to mass effect and compression and vascular compromise of
the cranial nerves.7
Pachymeningitis may occur as a direct extension of leptomeningitis in several
infections including Lyme disease, syphilis, and tuberculosis; in these cases, the
presence of prominent CSF inflammation and an acute to subacute time course
suggest the infectious mechanism. Isolated
dural involvement is more commonly
associated with autoimmune and
rheumatologic diseases.9 Sarcoidosis,
in addition to causing aseptic
leptomeningitis, is an important cause of
pachymeningitis. In the previously
mentioned imaging study of 100 patients
with neurosarcoidosis, pachymeningitis
was reported in 32%.11 Neurosarcoidosis
may cause both diffuse and nodular
patterns (FIGURE 10-6) and may be
associated with simultaneous
leptomeningitis or obstructive
hydrocephalus.16
IgG4-related disease is another
important cause of pachymeningitis.
It is a chronic progressive autoimmune
multisystem disease that frequently FIGURE 10-5
involves the pancreas, biliary tract, and Axial postcontrast T1-weighted MRI
showing dural enhancement with
kidneys. Pachymeningitis is the most diffuse smooth dural thickening
common neurologic manifestation, either (arrows) in a patient with idiopathic
as isolated dural disease or with extension pachymeningitis.

FIGURE 10-6
Three patients with various forms of dural neurosarcoidosis. Coronal postcontrast
T1-weighted MRI showing right cavernous sinus dural masslike inflammation (A, red arrow) in
a patient with right abducens and trigeminal palsies due to possible neurosarcoidosis. Axial
(B) and coronal (C) postcontrast T1-weighted MRI showing dural-based inflammation and
focal pachymeningeal enhancement (B, C, red arrows) and adjacent leptomeningeal
enhancement (B, C, yellow arrows) in two patients with neurosarcoidosis.
to adjacent orbital, sinus, and hypothalamopituitary tissues. Dural lesions in

IgG4-related disease may be hyperdense on noncontrast CT, mimicking subdural
hematoma (FIGURE 10-7). On MRI, lesions may have nodular enhancement and
thickening, which may be misdiagnosed as meningioma if focal (FIGURE 10-8).
IgG4-related disease (and neurosarcoidosis) can cause hypophysitis and
cavernous sinus disease, with nodular enhancing lesions (FIGURE 10-9).
Idiopathic hypertrophic pachymeningitis has been reported with varying
presentations and with both diffuse and nodular involvement. As the name
suggests, the radiographic and pathologic pattern is hypertrophic, but no
identifiable underlying disease is identified. Many cases of idiopathic
hypertrophic pachymeningitis are likely due to previously undiagnosed
IgG4-related disease.17
Granulomatosis with polyangiitis, often associated with antineutrophil
cytoplasmic antibodies (ANCAs), may also cause pachymeningitis. CNS
involvement may occur in up to 15% of patients with ANCA-associated
vasculitis. Hypertrophic pachymeningitis is a typical CNS manifestation, often
accompanied by multiple ipsilateral cranial neuropathies. The dura may be
affected by direct extension from involved sinuses, which can be a clue to the
diagnosis (FIGURE 10-10).18 The term CNS-limited ANCA-associated vasculitis has
been used for a specific subset of patients with myeloperoxidase antibody–
ANCA-positive vasculitis, with a predilection for older women in a hypertrophic
meningitis pattern with less severe neurologic damage and lower rates of
generalized disease.19
Encephalitis
Encephalitis refers to inflammation of the brain parenchyma. It may be diffuse or
focal. Acute encephalitis is frequently caused by viruses, with herpes simplex
virus (HSV) type 1 and West Nile virus being the most common. Encephalitis
may also occur in the setting of systemic autoimmune diseases, such as
sarcoidosis or Behçet syndrome. Autoimmune encephalitis is an umbrella term
for a group of noninfectious, immune-mediated brain disorders that typically
262 FEBRUARY 2023

KEY POINTS
● IgG4-related disease (as

well as neurosarcoidosis)
can cause hypophysitis and
cavernous sinus disease.
● Direct extension of
granulomatous inflammation
from sinus to dura is a clue to
antineutrophil cytoplasmic
antibody–associated
vasculitis.
● CNS-limited
antineutrophil cytoplasmic
antibody–associated
vasculitis is typically
associated with a
hypertrophic meningitis in
older women with positive
myeloperoxidase antibody.
FIGURE 10-7
Axial brain CT without contrast in a patient with biopsy-proven IgG4-related disease. A,
Brain window showing a left frontal dural hyperdensity (arrow) that was initially
misdiagnosed as a small subdural hematoma. B, Bone window of the same CT scan to
demonstrate the lack of changes in the overlying bone that might be seen in other diseases
such as meningioma.
FIGURE 10-8
Axial postcontrast T1-weighted MRI showing numerous dural-based lesions along the
bilateral convexity (A, B, arrows) and falx (A, arrowhead ) in a patient with hypertrophic
pachymeningitis secondary to biopsy-proven IgG4-related disease.

KEY POINTS present with subacute (over 6 to

12 weeks) cognitive or behavioral changes,
● Brain MRI in NMDA
receptor encephalitis is
seizures, or focal neurologic deficits.20
normal in most patients. Autoimmune encephalitis most commonly
affects the cortex and deep gray matter but
● Compared with may also involve white matter, meninges,
autoimmune encephalitis,
or the spinal cord.21 The underlying
herpes simplex virus
encephalitis is more likely to pathophysiology may involve a pathologic
be unilateral or asymmetric autoantibody to neuronal or glial surface
and to have accompanying antigens, a cytotoxic process targeting
diffusion-weighted imaging onconeural intracellular antigens with an
restriction and
enhancement. accompanying paraneoplastic antibody
marker, an unknown T cell–mediated
● Lack of prodromal process, or a yet unidentified
symptoms, rapid clinical autoantibody.12
improvement with
antiseizure medications
Autoimmune encephalitis may be
FIGURE 10-9
alone, and noninflammatory Axial postcontrast T1-weighted MRI
categorized based on the topography of
CSF are all clues to showing a pituitary lesion and dural pathology (FIGURE 10-1).
distinguish peri-ictal MRI thickening and enhancement (arrows)
changes from limbic in a patient with hypertrophic LIMBIC AUTOIMMUNE ENCEPHALITIS. Limbic
autoimmune encephalitis. pachymeningitis secondary to
autoimmune encephalitis is characterized
biopsy-proven IgG4-related disease.
by anterograde memory loss, behavioral
or psychiatric symptoms, and
seizures because of the involvement of the medial temporal lobes. Typical
imaging findings include T2 hyperintensity in bilateral mesial temporal lobes
(FIGURE 10-11). Limbic encephalitis due to LGI1 is one of the most commonly
identified forms of autoimmune encephalitis with this imaging appearance,
although several other antibody associations have been noted with bilateral
temporal lobe predilection. Importantly, brain MRI is normal in most patients
FIGURE 10-10
Axial (A) and coronal (B) postcontrast T1-weighted MRI showing frontal and maxillary sinus
inflammation (A, B, arrows) and subjacent dural enhancement (A, B, arrowheads) in a patient
with multiple cranial neuropathies as the initial presentation of granulomatous polyangiitis
(antineutrophil cytoplasmic antibody positive).
264 FEBRUARY 2023

with NMDA receptor encephalitis despite typical involvement of limbic (among
other) areas and the frequency of seizures. It is estimated that up to 89% of
patients with NMDA receptor encephalitis have normal initial MRI, and up to
77% upon follow-up MRI (median Day 25).22
HSV encephalitis is a potential radiographic mimicker of limbic autoimmune
encephalitis. In addition to the clinical clues of a more fulminant clinical course
and fever at presentation, on MRI HSV encephalitis is more likely to be unilateral
or asymmetric and to have accompanying DWI restriction and enhancement
(FIGURE 10-12). When HSV encephalitis MRI changes are bilateral, extensive
involvement is typically seen beyond the medial temporal lobe on the side
initially affected before spreading to the contralateral temporal lobe.23,24
Another challenging radiographic differential diagnosis includes the reversible
MRI changes that can be seen in the hippocampi and deep gray matter after
seizure activity from any cause, especially given the frequency of seizures as a
complication of autoimmune encephalitis. These peri-ictal MRI changes can
include T2-hyperintense signal, restricted diffusion on DWI, postcontrast T1
enhancement, and mass effect from edema. The MRI changes may persist for
2 weeks to 5 months before either complete resolution or evolution into gliosis
and focal atrophy occur.25 The lack of prodromal symptoms before the seizure,
rapid clinical improvement with antiseizure medications alone, and
noninflammatory CSF are helpful clues to differentiate peri-ictal MRI changes
from limbic autoimmune encephalitis.
NMDA receptor encephalitis is the most common cause of autoimmune
encephalitis. It typically presents with a flulike prodrome followed by an onset of
psychiatric and behavioral changes such as anxiety, depression, and psychosis
and progresses over time to amnesia, seizures, autonomic dysfunction, and
abnormal involuntary movements such as orofacial dyskinesias.21 Although MRI
in NMDA receptor encephalitis is often normal, it can sometimes present
as large, poorly demarcated lesions with no or minimal enhancement, located
throughout the brain including the cortex, white matter, and deep gray matter.21
Patients with Hashimoto encephalopathy present with altered mental status,
seizures, myoclonus, hallucinations, or strokelike episodes. Serum antithyroid
FIGURE 10-11
Axial T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance images
demonstrating abnormal hyperintensities (arrows) in the bilateral insula and mesiotemporal
lobes in a patient with seronegative limbic encephalitis. No associated abnormality was
seen on diffusion-weighted imaging (DWI) (not shown).

FIGURE 10-12
Axial brain MRI of a patient with herpes simplex virus encephalitis. A, T2 fluid-attenuated
inversion recovery (FLAIR) magnetic resonance images showing markedly asymmetric
abnormal hyperintensity (arrows) in the left insula, medial temporal, and inferior frontal areas.
B, Diffusion-weighted imaging (DWI) showing restricted diffusion (arrows) in the same areas.
FIGURE 10-13
Axial T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance images showing
scattered hyperintensities (arrows) in the right parietal lobe, bilateral insula, bilateral
thalami (more prominent on the left), and left midbrain in a patient with encephalitis
secondary to exposure to immune checkpoint inhibitor therapy.
266 FEBRUARY 2023

peroxidase or thyroglobulin antibodies or both are elevated, although this is KEY POINTS
associated with subclinical or only mildly overt thyroid disease. These thyroid
● About 50% of patients
antibodies are thought to be a biomarker of an immune-mediated process but with Hashimoto
are not part of the CNS pathology. About 50% of patients with Hashimoto encephalopathy have a
encephalopathy have a normal brain MRI. The Graus 2016 criteria for diagnosis normal brain MRI.
of Hashimoto encephalopathy stipulate that MRI is normal or shows only
● Fludeoxyglucose positron
nonspecific findings such as cerebral atrophy and subcortical white matter
emission tomography
changes.20 Those with hippocampal or temporal lobe hyperintensities on FLAIR (FDG-PET) of the brain can
should raise the suspicion for either postictal edema or seronegative be a more sensitive
autoimmune encephalitis.20,26 biomarker than brain MRI for
When autoimmune encephalitis is suspected but brain MRI is normal, detecting focal or multifocal
brain abnormalities in
fludeoxyglucose positron emission tomography (FDG-PET) of the brain can be a autoimmune encephalitis.
more sensitive biomarker in detecting focal or multifocal brain abnormalities,
with studies reporting a sensitivity of 87% compared with 56% for MRI.5 Most ● A gradient of anterior
PET imaging in limbic autoimmune encephalitis shows abnormalities within the hypermetabolism to
posterior cortical
basal ganglia and mesiotemporal lobes, with varying hypermetabolism or hypometabolism, especially
hypometabolism depending on the syndrome and stage of the illness. A gradient in the medial and lateral
of anterior hypermetabolism to posterior cortical hypometabolism, especially in occipital lobes, has been
the medial and lateral occipital lobes, has been described in NMDA receptor described in NMDA receptor
encephalitis.
encephalitis.27 In Rasmussen encephalitis, a pattern of hemispheric
hypometabolism, out of proportion to the atrophy seen on MRI, can help make ● Hypometabolic PET
the diagnosis.5 Despite the utility of PET in diagnosing these forms of patterns are not specific to
autoimmune encephalitis, clinicians must be aware that hypometabolic foci are autoimmune encephalitis
nonspecific and may be seen commonly postictally and in older patients with and are seen commonly in
the postictal state and in
neurodegenerative disease.28 older patients with
Although the presence of bilateral temporal lobe FLAIR hyperintensities is neurodegenerative disease.
typical enough to make a diagnosis of limbic autoimmune encephalitis even in
the absence of neuronal antibodies (once viral etiologies have been sufficiently ● Once viral causes are
ruled out, the presence of
ruled out), other MRI patterns including cortical, subcortical, deep (striatal and bilateral temporal lobe
diencephalic), brainstem, and cerebellar involvement are less specific and FLAIR hyperintensities is
support only possible or probable autoimmune encephalitis unless a clinically sufficient to diagnose
relevant autoantibody is positive.20 definite limbic autoimmune
encephalitis even in the
absence of neuronal
SUBCORTICAL IMMUNE-MEDIATED DISEASE. Subcortical immune-mediated disease is antibodies.
most commonly caused by demyelinating disorders such as acute disseminated
encephalomyelitis (ADEM), myelin oligodendrocyte glycoprotein (MOG)–
associated disorder, and multiple sclerosis. Rarely, however, autoimmune
encephalitis can present with subcortical predominance, for example, with
immune checkpoint inhibitor–induced encephalitis (FIGURE 10-13). Conversely,
cortical involvement or “cortical encephalitis” can sometimes occur with
predominantly subcortical syndromes, especially ADEM and MOG-associated
disorder (FIGURE 10-14).
An important diagnostic consideration for subacute, predominantly
subcortical encephalitis is progressive multifocal leukoencephalopathy caused by
JC virus infection, most commonly associated with immunocompromise
including human immunodeficiency virus (HIV) infection, lymphoproliferative
diseases, and natalizumab therapy in patients with multiple sclerosis. MRI
FLAIR sequences are the most sensitive for detecting progressive multifocal
leukoencephalopathy lesions, which typically involve subcortical and
juxtacortical white matter hyperintensities with early involvement of the U fibers.

FIGURE 10-14
Axial T2 fluid-attenuated inversion recovery (FLAIR) (A) and postcontrast T1-weighted (B) MRI
demonstrating “fluffy” cortical and subcortical lesions (A, red arrowheads) with associated
parenchymal (B, red arrows) and leptomeningeal enhancement (B, yellow arrows) in a patient
with myelin oligodendrocyte glycoprotein–associated acute disseminated encephalomyelitis
(ADEM) with concurrent positive anti–N-methyl-D-aspartate (NMDA) receptor antibody.
Lesions are usually isointense or hypointense lesions on T1-weighted imaging with

variable enhancement depending on the state of the host’s immune system
(nonenhancing with severe immunocompromise and patchy enhancement in
patients with mild immunosuppression or reconstituting immune systems)
(FIGURE 10-15). Serial imaging shows asymmetric enlargement of lesions,
coalescence, and appearance of new lesions, hence the name multifocal.29
MULTIPLE AND CONFLUENT CORTICAL AND SUBCORTICAL DISEASE. Multiple and

confluent cortical and subcortical FLAIR hyperintensities are a hallmark of
encephalitis with autoantibodies to γ-aminobutyric acid type A (GABAA)
receptor, typically presenting as drug-resistant epilepsy and epilepsia partialis
continua.30 In contrast to GABAB receptor encephalitis, which tends to show no
abnormalities on MRI, GABAA receptor encephalitis demonstrates these
multifocal lesions in the frontal and temporal lobes and bilateral cingulate gyri
without abnormal enhancement, diffusion restriction, or mass effect (FIGURE 10-16).31
In children with refractory epilepsia partialis continua, subcortical T2 changes
restricted to one hemisphere should raise concern for Rasmussen encephalitis,
which typically presents early on as edema and nonenhancing hyperintensity on
FLAIR imaging, especially in the insular and peri-insular regions, followed by
severe hemispheric atrophy as the disease progresses.32
INVOLVEMENT OF DEEP GRAY MATTER. Involvement of the deep gray matter in

encephalitis may be divided into striatal and diencephalic. Clinically, these
syndromes are easily distinguished from limbic encephalitis. Striatal encephalitis
tends to manifest with movement disorders such as chorea in association with
anticollapsin response mediator protein-5 (CRMP5 or CV2) antibodies, typically
268 FEBRUARY 2023

KEY POINT
● Multiple and confluent

cortical and subcortical
FLAIR hyperintensities are a
hallmark of encephalitis
with autoantibodies to
γ-aminobutyric acid type A
(GABAA) receptor.
FIGURE 10-15
Axial T2 fluid-attenuated inversion recovery (FLAIR) (A) MRI showing right frontal
juxtacortical and subcortical T2-hyperintense signal change (A, arrows) and axial
postcontrast T1-weighted (B) MRI showing central hypointense signal with patchy
enhancement (B, arrows) in a patient with biopsy-proven progressive multifocal
leukoencephalopathy without known immunocompromise.
FIGURE 10-16
Axial T2 fluid-attenuated inversion recovery (FLAIR) MRI showing several abnormal cortical
and subcortical hyperintensities (arrows), without enhancement (not shown), in a patient
with γ-aminobutyric acid type A (GABAA) receptor encephalitis.
Images courtesy of Christine Gill, MD.

heralding an occult small cell lung cancer. Cases of extensive T2-hyperintense

symmetric signal affecting the bilateral caudate and putamen have been reported
with extension into the anterior limbs of the internal capsules.33,34 Dopamine D2
receptor encephalitis also manifests with basal ganglia T2 hyperintensities on
MRI in 50% of patients with this autoantibody and mainly presents in adolescents
as subacute parkinsonism and dystonia after an infection such as β-hemolytic
streptococcus and mycoplasma.35 Diencephalic encephalitis manifests with sleep
disturbances (narcolepsy-cataplexy) and autonomic and hormonal disturbances
due to the involvement of the hypothalamus. Anti-Ma2–associated encephalitis,
commonly associated with testicular germ cell tumors, characteristically targets
the diencephalon. Brain MRI is abnormal in up to 74% of patients with positive
anti-Ma antibodies; in those with a diencephalic presentation, MRI may show T2
hyperintensities with variable enhancement in the medial thalami and midbrain
(FIGURE 10-17).36 For clinical or radiographic subacute hypothalamic
inflammatory syndromes, neurosarcoidosis should also be considered;
involvement of the pituitary stalk and gland in addition to the hypothalamus can
be a clue to this diagnosis.
Glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune
encephalitis that may manifest with meningitis, encephalitis, myelitis, and optic
neuritis.37 It has been associated with periventricular linear radial enhancement
FIGURE 10-17
Axial T2 fluid-attenuated inversion recovery (FLAIR) (A) and axial postcontrast T1-weighted
(B) MRIs revealing a suprasellar, diencephalic T2-hyperintense lesion (A, arrows) that is avidly
enhancing (B, arrows), with mass effect and resultant obstructive hydrocephalus in a patient
with anti-Ma2 encephalitis and nonseminomatous germ cell tumor found in the mediastinum.
270 FEBRUARY 2023

on MRI postcontrast T1-weighted imaging, a distinctive radiographic finding KEY POINTS
that should raise suspicion for the culprit autoantibody; this finding has also been
● Striatal encephalitis with
described in the cerebellum and brainstem.37,38 Patients with GFAP astrocytopathy anti-collapsin response
may also harbor other autoantibodies such as NMDA receptor IgG (CASE 10-1). mediator protein 5 (CRMP5
or CV2) antibodies may be
BRAINSTEM AND CEREBELLAR INFLAMMATORY PATHOLOGIES. Brainstem and associated with extensive
T2-hyperintense symmetric
cerebellar inflammatory pathologies tend to present with acute to subacute
signal affecting the bilateral
ataxia, cranial neuropathies, bulbar dysfunction, and pyramidal weakness.39 caudate and putamen.
Inflammation of hindbrain structures (pons, medulla, and cerebellum) is
sometimes termed rhombencephalitis, but many processes also affect the ● Paraneoplastic
midbrain. For simplicity, many authors use the term brainstem encephalitis to diencephalic encephalitis
associated with Ma2
indicate midbrain and hindbrain inflammation. Of note, for posterior fossa antibodies may cause T2
structures, subtle T2 hyperintensity may be more easily appreciated on hyperintensities in the
conventional T2-weighted MRI than on FLAIR sequences. medial thalami and
Listeria monocytogenes is the most common cause of infectious brainstem midbrain.
encephalitis, with tropism for the tissue surrounding the fourth ventricle. On ● Glial fibrillary acidic
MRI, T1 hypointensity and T2 hyperintensity are typical; if present, rim- protein (GFAP)
enhancing lesions with central restricted diffusion suggestive of abscess astrocytopathy is associated
are a strong clue to the diagnosis. Although HSV type 1 preferentially involves with a hallmark MRI finding
of periventricular linear
the limbic system, extralimbic brainstem involvement may also occur. Acute to
radial enhancement on
subacute onset with fever and inflammatory CSF should prompt consideration postcontrast T1-weighted
and treatment for Listeria infection or HSV encephalitis in cases with clinical and sequences.
radiographic evidence for brainstem encephalitis until these are excluded.39
Autoimmune brainstem pathologies are diverse, and MRI can offer ● For posterior fossa
structures, subtle T2
helpful clues, even if normal (TABLE 10-140,41). Behçet syndrome is a systemic hyperintensity may be more
vascular inflammatory disease with hallmark features including recurrent easily appreciated on
oral ulcers and combinations of genital ulcers, uveitis, or skin changes. When conventional T2-weighted
the CNS is involved (neuro-Behçet syndrome), the disorder has a predilection MRI than on FLAIR
sequences.
for the corticospinal tracts in the midbrain and pons, with variable rostral
extension into the internal capsule or caudal extension into the medulla and spinal ● Rim-enhancing lesions
cord. The underlying inflammatory process in venules leads to an MRI pattern with central restricted
including T2 hyperintensity and edema sparing the red nucleus, patchy diffusion suggestive of
abscess are clues to Listeria
postcontrast T1 enhancement, and punctate foci of susceptibility artifact on SWI
infection as the cause of
(FIGURE 10-19).42 brainstem encephalitis.
Another immune-mediated syndrome with a tropism for the brainstem is
chronic lymphocytic inflammation with pontine perivascular enhancement ● Neuro-Behçet syndrome
responsive to steroids (CLIPPERS). This idiopathic immune-mediated may be associated with T2
hyperintensity in the ventral
disorder is marked by a subacute brainstem syndrome with MRI showing a pons and midbrain, sparing
unique pattern of multiple small (<3 mm) FLAIR–hyperintense foci with the red nucleus.
matching homogenous or curvilinear enhancement mostly restricted to the
pons (although it may extend rostrally or caudally). By definition, the clinical
syndrome and lesions improve markedly with corticosteroids.43 Pathologies
that can radiographically mimic CLIPPERS include CNS lymphoma and
granulomatous diseases such as CNS tuberculosis and neurosarcoidosis, all of
which may have a similar punctate or curvilinear enhancement pattern
reflecting a perivascular location and may respond (at least initially) to
corticosteroids (FIGURE 10-20). CNS tuberculosis and neurosarcoidosis are
often associated with meningitis and accompanying leptomeningeal
enhancement, which is less common with CLIPPERS. Susac syndrome is an
endotheliopathy defined by a triad of encephalopathy, retinal vasculitis, and

CASE 10-1 A 23-year-old woman developed headache and confusion followed by

bursts of aggression, forgetfulness, and insomnia over a few days. In the
emergency department, she was tachycardic, tachypneic, and febrile to
38.6°C (101.5°F). She was started on empiric treatment for meningitis and
encephalitis with antibiotics and acyclovir. She progressed rapidly to
stupor and developed abnormal stereotypical movements of bilateral
eyelids, mouth opening and closing, and inverse ocular bobbing. Lumbar
puncture revealed normal glucose adjusted for serum, an elevated
protein concentration of 135 mg/dL, and lymphocytic pleocytosis with
331 cells/mm3; infectious multiplex polymerase chain reaction (PCR)
assay was negative which prompted discontinuation of the empiric
antibiotics and acyclovir. Brain MRI
with contrast revealed diffuse
leptomeningeal enhancement, as
well as periventricular linear radial
enhancement (FIGURE 10-18). EEG was
significant for diffuse slowing without
epileptiform discharges. Autoimmune
encephalitis was suspected, and
empiric treatment was initiated with
methylprednisolone 1000 mg IV daily
for 5 days and concomitant IV
immunoglobulins (IVIg) 2 g/kg
administered in divided doses over
2 consecutive days. The
autoantibody panel returned positive
for both anti–N-methyl-D-aspartate
(NMDA) receptor antibody and
anti–glial fibrillary acidic protein FIGURE 10-18
(GFAP) antibody in both the serum Axial postcontrast T1-weighted MRI
and CSF. Tumor screening with showing diffuse leptomeningeal
enhancement with characteristic
fludeoxyglucose positron emission radial linear enhancement
tomography (FDG-PET) of her whole perpendicular to the lateral ventricles
body and transvaginal ultrasonography (arrows) in the patient in CASE 10-1 with
was negative. Because of paroxysmal N-methyl-D-aspartate (NMDA)
receptor encephalitis with
sympathetic hyperactivity requiring concomitant glial fibrillary acidic
intensive care, the patient was started protein (GFAP) meningoencephalitis.
sequentially on rituximab followed
2 weeks later by cyclophosphamide.
COMMENT It is most likely that this patient’s MRI and CSF findings are driven by GFAP
meningoencephalitis, whereas her clinical picture is driven by NMDA
receptor encephalitis. The patient improved slowly with aggressive
symptomatic treatment of her autonomic instability, as well as the
immunosuppressant therapies. She was discharged from the hospital after
several months in the ICU with a tracheostomy and a percutaneous
gastrostomy tube for enteral feeding with plans for physical therapy.
272 FEBRUARY 2023

Brainstem Inflammatory Syndromesa TABLE 10-1
Characteristics Inflammatory differential diagnosis Noninflammatory differential diagnosis
Topography and size of lesion
Well-defined, peripheral, and ovoid, Multiple sclerosis Ischemic infarcts

especially when affecting specific
tracts (medial longitudinal fasciculus,
trigeminal fascicles)
Circumventricular lesion (abutting third Neuromyelitis optica Not applicable (NA)

and fourth ventricles) spectrum disorder (NMOSD)
Linear lesions along the dorsal medulla
(area postrema)
Extension into the diencephalon NMOSD, neuro-Behçet syndrome Wernicke encephalopathy, Whipple
disease
Space-occupying lesion Tumefactive demyelination, central Glioma

nervous system (CNS) vasculitis, CNS
histiocytosis
Asymmetric, hazy, or “fluffy” lesions Myelin oligodendrocyte glycoprotein Whipple disease, herpes simplex virus
that are poorly demarcated (MOG)-associated disorder, acute (HSV) encephalitis, small vessel
disseminated encephalomyelitis ischemic changes (especially when
(ADEM), neuro-Behçet syndrome central pontine)
Brainstem atrophy Chronic multiple sclerosis or NMOSD, Neurodegenerative causes such as

neuro-Behçet syndrome, chronic Alexander disease
lymphocytic inflammation with pontine
perivascular enhancement responsive
to steroids (CLIPPERS)
Pattern of enhancement
Punctate and curvilinear CLIPPERS, Susac syndrome NA
Nodular Neurosarcoidosis, CNS vasculitis NA
Open ring CNS demyelination NA
Meningeal and cranial neuropathies Neurosarcoidosis, IgG4-related Tuberculosis meningitis, Lyme

disease, vasculitis meningitis
Other sequences
Diffusion restriction Acute demyelination, neuro-Behçet Lymphoma, abscess, acute ischemia,

syndrome, Susac syndrome, vasculitis central pontine myelinolysis
T1 hypointensity NMOSD NA
Microhemorrhages on Inflammatory cerebral amyloid HSV encephalitis

susceptibility-weight imaging (SWI) or angiopathy (reported in the thalamus
gradient echo (GRE) and cerebellum)41
a
Data from Law LY, et al, Neurology.40

FIGURE 10-19
Brain MRI of a patient with neuro-Behçet syndrome. Axial T2-fluid-attenuated inversion
recovery (FLAIR) MRI showing abnormal T2-hyperintense signal (A, B, C, D, yellow arrows) in
the right more than left internal capsule (A), midbrain (B), pons (C), and medulla (D). Coronal
(E) and axial (F) T2-weighted MRI highlights the corticospinal tract tropism (E, red arrows)
and sparing of red nuclei (F, red arrowheads).
sensorineural hearing loss. It may involve the brainstem with punctate

T2-hyperintense foci and curvilinear enhancement; unlike CLIPPERS,
however, the foci restrict diffusion acutely and are often accompanied by
T2-hyperintense round lesions in the corpus callosum (snowball lesions)
(FIGURE 10-21).44
Aquaporin-4 IgG-positive NMOSD may present with a brainstem
syndrome, typically with symptoms referable to the area postrema in the
medulla or circumventricular region around the third ventricle, which is
rich in aquaporin-4 channels. MRI demonstrates T2 hyperintensity in the
dorsal medulla or rostral midbrain, with minimal or patchy enhancement
(FIGURE 10-22). MOG-associated disorder may also present with an area postrema
274 FEBRUARY 2023

FIGURE 10-20
Axial postcontrast T1-weighted (A) MRIs showing multifocal punctate “scattershot”
lesions (A, arrows) with accompanying abnormal hyperintense signal (B, arrows) on
axial T2 fluid-attenuated inversion recovery (FLAIR) images throughout the brainstem,
cerebellum, and cerebral hemispheres, as well as spinal cord (not shown) in a patient
with probable neurosarcoidosis.
syndrome. Both NMOSD and MOG-associated disorder may present with

associated optic neuritis or longitudinally extensive transverse myelitis, which
are clues to the diagnosis.40
Some patients present with clinical symptoms and signs that localize to the
brainstem, but MRI is normal, initially and on subsequent scans. Several
immune-mediated brainstem pathologies may be MRI negative. Bickerstaff
brainstem encephalitis is defined by a triad of ataxia, bilateral external
ophthalmoplegia, and encephalopathy and is considered a variant of Guillain-
Barré syndrome. As with the related Guillain-Barré syndrome variant
Miller-Fisher syndrome, anti-GQ1b antibody in the serum or CSF is specific
for the disease. Although MRI is usually normal, Bickerstaff brainstem
encephalitis can be associated with MRI changes in up to 30% of patients,

FIGURE 10-21
Axial (A) and sagittal (B) T2 fluid-attenuated inversion recovery (FLAIR) sequences
demonstrating “snowball” T2 hyperintensities in the corpus callosum (A, B, arrows) in a
patient with Susac syndrome.
including waxing and waning T2-hyperintense lesions throughout the brainstem

(especially in the midbrain).40
Patients with anti-IgLON5 disease present with parasomnia and breathing
difficulty during sleep preceded or accompanied by bulbar symptoms resembling
motor neuron disease, gait abnormalities, oculomotor problems resembling
progressive supranuclear palsy, and cognitive decline. Brain MRI is typically
unremarkable but may show mild atrophy of the brainstem and cerebellum.45
FIGURE 10-22
Coronal T2-weighted (A) MRI showing abnormal hyperintensity in the dorsal medulla
(A, arrow) with corresponding coronal T1 postcontrast enhancement (B, arrow) in a patient
with aquaporin-4 IgG positive neuromyelitis optica spectrum disorder presenting with area
postrema syndrome (refractory vomiting).
276 FEBRUARY 2023

Paraneoplastic brainstem encephalitis secondary to onconeural antibodies KEY POINTS
is also associated with a normal or nonspecific brain MRI. Kelch-like protein
● MRI is often normal early
11 antibody in seminoma-associated paraneoplastic encephalitis presents in the course of
with ataxia and cochleovestibulopathy but normal MRI.46 Anti-ANNA1 paraneoplastic cerebellar
(anti-Hu)–associated encephalitis, which classically presents with limbic degeneration although mild
encephalitis and neuronopathy in the setting of small cell lung cancer, can T2 hyperintensities may be
seen in the cerebellar
present as isolated brainstem encephalitis with normal MRI and central
hemispheres.
hypoventilation (Ondine’s curse).47 Anti-ANNA2 (anti-Ri) is an onconeural
antibody targeting intracellular antigens usually associated with breast cancer. ● The most commonly
Patients may present with opsoclonus-myoclonus-ataxia syndrome, but brain associated autoantibodies
MRI typically either is normal or shows nonspecific changes in the brainstem.48 with autoimmune cerebellar
ataxia are anti–glutamic acid
Immune-mediated cerebellar syndromes may be paraneoplastic or decarboxylase 65 (GAD65),
autoimmune. Paraneoplastic cerebellar degeneration is the second most common anti–contactin-associated
CNS paraneoplastic syndrome following limbic encephalitis; it is associated proteinlike 2 (CASPR2), and
with nearly 30 different autoantibodies and multiple types of malignancy.49,50 anti–metabotropic
glutamate receptor
Rapidly progressive cerebellar ataxia is typically associated with anti-Yo (also (mGLuR1).
known as Purkinje cell antibody 1) antibody, whereas a more diffuse
encephalomyelitis is associated with ANNA1 (anti-Hu) antibodies.50 MRI ● Approximately 50% of
findings depend on the phase of the disease but are typically mild, with acute patients with
neuropsychiatric lupus have
paraneoplastic cerebellar degeneration showing normal MRI or mild T2
abnormal brain MRI, most
hyperintensities in the cerebellar hemispheres, whereas the more chronic phases commonly manifesting as
demonstrate cerebellar atrophy best seen on T1 sequences (FIGURE 10-23).50 nonspecific white matter
Autoimmune cerebellar ataxias include gluten ataxia, postinfectious cerebellitis periventricular and
subcortical T2
(especially in children), and opsoclonus-myoclonus-ataxia syndrome, with or
hyperintensities.
without causative neuronal antibodies.51 Some of the most commonly associated
autoantibodies with autoimmune cerebellar ataxia are anti–glutamic acid
decarboxylase 65 (GAD65), anti–contactin-associated proteinlike 2 (CASPR2),
and anti–metabotropic glutamate receptor (mGLuR1). Most of these have normal
MRI early in the disease but may demonstrate enhancement or T2-hyperintense
FIGURE 10-23
Axial (A) and sagittal (B) T1-weighted MRIs showing diffuse cerebellar atrophy (A, B, inside
rectangles) in a patient with subacute ataxia in the setting of presumed seronegative
paraneoplastic cerebellar degeneration with occult endometrial cancer.

signal along cerebellar folia (FIGURE 10-24); patients with autoimmune cerebellar
ataxias develop cerebellar atrophy over time, especially with GAD65.52
Systemic Autoimmunity With Neuroimaging Abnormalities

Several neurologic syndromes and imaging abnormalities have been associated
with systemic autoimmune and connective tissue diseases. Neuropsychiatric
manifestations of systemic lupus erythematosus (SLE) are attributed to multiple
etiologies such as vasculopathy, thromboembolism, demyelination, and direct
neural autoimmune damage.13 Concurrent antiphospholipid syndrome in patients
with SLE increases the risk of large and small vessel infarcts and arterial stenosis
and is associated with more abnormalities on MRI than in patients with SLE but
without antiphospholipid syndrome.53 Approximately 50% of patients with
neuropsychiatric lupus have abnormal brain MRI, most commonly manifesting as
white matter periventricular and subcortical T2 hyperintensities. These changes
are nonspecific and indistinguishable from microvascular ischemic changes seen
with aging or leukoaraiosis.13 The central vein sign is an imaging biomarker for
multiple sclerosis in which a vein passing through the white matter lesion is
visualized on SWI in keeping with the venular origin of inflammatory lesions; this
finding is generally absent in SLE.54 Cerebral atrophy and confluent white matter
lesions that are either periventricular or striatal have also been reported.12,55
Patients can also have imaging abnormalities related to complications such as
postictal changes after seizures or large vessel occlusions.56 No clear autoantibodies
have been established with direct CNS pathogenicity in SLE; however, elevated
antiribosomal P antibodies have been associated with CNS manifestations of SLE,
and at least some cases of neuropsychiatric SLE are caused by NMDA receptor
encephalitis with corresponding CSF NMDA receptor IgG antibodies.57,58
FIGURE 10-24
Brain MRI from two patients with immune-mediated cerebellar ataxia. Axial (A) and coronal
(B) postcontrast T1-weighted MRI showing diffuse leptomeningeal enhancement most
prominently in the bilateral cerebellar hemispheres (A, B, arrows) in a patient with
postinfectious cerebellitis. Axial T2 fluid-attenuated inversion recovery (FLAIR) (C) sequence
showing subtle sulcal T2 nonsuppression along the cerebellar folia with associated
postcontrast T1 enhancement (D, arrows) in a patient with acute cerebellar ataxia with
septin and immunoglobulin-G (IgG) autoantibodies specific for ρ GTPase activating protein
26 (ARHGAP26, also known as GTPase regulator associated with focal adhesion kinase
[GRAF1]) (GRAF/ARHGAP) antibodies in CSF.
278 FEBRUARY 2023

Sjögren syndrome (SS) is a systemic inflammatory disease affecting the KEY POINTS
exocrine glands. CNS involvement in Sjögren syndrome historically has been
● Neuromyelitis optica
attributed to immune-mediated demyelination and vasculopathy. Subcortical spectrum disorder (NMOSD)
and periventricular white matter T2 hyperintensities are the most common MRI may occur in association
feature, present in up to 70% of patients with Sjögren syndrome.59 Compared with Sjögren syndrome, and
with multiple sclerosis, basal ganglia lesions are more common and corpus patients with optic neuritis
or transverse myelitis should
callosum lesions are rare; however, the findings are nonspecific, and the link to
be tested for serum
Sjögren syndrome is unclear.13,60 Relapsing demyelinating syndromes in patients aquaporin-4 IgG and myelin
with Sjögren syndrome are most often caused by comorbid multiple sclerosis or oligodendrocyte
NMOSD with MRI features typical for those diseases. All patients with Sjögren glycoprotein IgG.
syndrome who have optic neuritis or transverse myelitis should be tested for
● Brain MRI is abnormal in
serum anti-aquaporin-4 IgG antibodies and MOG IgG (anti–myelin 95% to 100% of patients with
oligodendrocyte glycoprotein antibody).13 CNS vasculitis.
Cerebral Vasculitis ● Digital subtraction

angiography is the most
CNS vasculitis refers to a group of inflammatory disorders that affect the walls of sensitive modality for
the cerebral vessels. They may be classified based on the size of the vessel vascular luminal changes in
affected, histopathologic findings, and the underlying inflammatory disease, CNS vasculitis, including
which may be systemic or isolated to the CNS. Primary angiitis alternating areas of stenosis
and dilation in at least two
of the CNS refers to inflammation affecting the vessels of the brain or spinal cord
separate vascular
without overt systemic vasculitis or an underlying potential cause. Secondary distributions.
CNS vasculitis occurs in the setting of a systemic vasculitis or CNS infection
(such as syphilis, tuberculosis, and varicella-zoster virus).61 Depending on the
cause, patients may present with subacute onset of progressive headache,
cognitive impairment, and neuropsychiatric disturbances or multifocal cerebral
infarcts across multiple vascular territories. Imaging may help differentiate CNS
vasculitis from mimics such as intracranial atherosclerosis, vasospasm such as in
reversible cerebral vasoconstriction syndrome (RCVS), and noninflammatory
vasculopathies such as cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy (CADASIL).61
MRI is abnormal in 95% to 100% of patients with CNS vasculitis, so a
negative MRI can essentially exclude the diagnosis. Typical findings include
infarcts of varying ages in multiple vascular territories with foci of restricted
diffusion acutely and T2-hyperintense foci from subacute to chronic
infarcts. Ischemic lesions are sometimes accompanied by subarachnoid or
intraparenchymal hemorrhagic lesions.62 Prominent meningeal gadolinium
enhancement is usually associated with negative angiography (because
of involvement of small meningeal arteries) but may have a more favorable
response to immunosuppressive therapy.61,63 Tumorlike infiltrative lesions
have been described in 4% to 11% of patients with primary angiitis of
the CNS with neoplasm as the most common differential diagnosis. A biopsy
is typically required for diagnosis in these cases (FIGURE 10-25).62,64
Angiography, whether magnetic resonance, CT, or digital subtraction
angiography (DSA), may be abnormal in cases involving medium to large
vessels. For large vessel irregularities (ie, carotid involvement in Takayasu or
giant cell arteritis), PET may be useful in confirming the inflammatory nature of
the vasculopathy (FIGURE 10-26).65 DSA is the most sensitive modality for
identifying vascular luminal changes, classically manifesting in CNS vasculitis as
alternating areas of stenosis and dilation in at least two separate vascular
distributions, a pattern sometimes referred to as beading (FIGURE 10-27). These

FIGURE 10-25
Axial T2 fluid-attenuated inversion recovery (FLAIR) (A) and axial postcontrast T1-weighted
(B) MRI reveal a right temporo-occipital hyperintense lesion with heterogenous enhancement
(A, B, arrows) in a patient with biopsy-proven central nervous system vasculitis.
changes are nonspecific, however, and may occur in noninflammatory medium

and large vessel vasculopathies. Furthermore, DSA cannot detect changes in
distal vessels of smaller caliber (<500 μm in diameter). One study of 60 patients
with primary angiitis of the CNS showed that 23% had biopsy-proven angiitis
without any visible imaging manifestations of vasculopathy.62 DSA carries
a small risk of complications including emboli, puncture site hematoma or
pseudoaneurysm, and radiation exposure.63 Brain and meningeal biopsy is
the gold standard for diagnosis, although it also has limited sensitivity. CSF
FIGURE 10-26
Imaging of a patient with Takayasu arteritis. Coronal (A) and axial (B) CT angiography images
of the neck showing diffuse irregularity of the carotid walls (A, B, arrows) with thickened
appearance and pseudoaneurysm of the left common carotid. C, Axial fludeoxyglucose
positron emission tomography (FDG-PET) of the same patient demonstrates abnormal FDG
uptake in both common carotid arteries (arrows), worse on the left, consistent with large
vessel vasculitis.
280 FEBRUARY 2023

KEY POINT
● High-resolution MRI with

vessel wall imaging may be
helpful in demonstrating
enhancement of the vessel
walls in vasculitis, but the
modality has limited
specificity.
FIGURE 10-27
Right common carotid injection sagittal (A) and anterior-posterior (B) digital subtraction
angiography shows diffuse medium vessel vasculopathy including luminal narrowing and
irregularities (A, B, red arrows) and “beading” (A, B, yellow arrowheads) in anterior and
posterior circulation in a patient with parainfectious central nervous vasculitis.
analysis may be helpful if inflammation is present but can be normal, even in

biopsy-proven cases.
High-resolution MRI with vessel wall imaging, also known as the black blood
sequence, was developed as a noninvasive method to assess vessel wall
inflammation through concurrent suppression of both CSF and luminal contrast
to highlight any postcontrast enhancement in affected vessel walls. In CNS
vasculitis, vessel wall imaging may show multifocal areas of concentric wall
thickening and enhancement, especially where a caliber change has occurred
(FIGURE 10-28). This method is not specific, however, because other
noninflammatory vasculopathies can present similarly, including intracranial
FIGURE 10-28
Sagittal high-resolution 3T MRI (A) and coronal magnetic resonance angiography (B) with
vessel wall imaging showing multifocal peripheral segmental concentric wall thickening and
enhancement (A, red arrows) and coronal oblique postcontrast vessel reconstruction
imaging showing diffuse vasculopathy with microaneurysm formation (B, yellow arrows) in a
patient with aseptic meningitis, increased intracranial pressure, headaches, and punctate
infarcts due to possible neurosarcoidosis.

atherosclerosis, arterial dissection, postthrombectomy changes, and RCVS. Some

studies suggest that atherosclerotic lesions typically have eccentric wall
enhancement whereas vasculitis shows circumferential enhancement. Vessel
wall enhancement in RCVS is typically subtle or absent.66
Although small vessel vasculitis can be hard to diagnose without a biopsy,
certain subtypes have characteristic imaging patterns that can aid in diagnosis.
Susac syndrome, as noted earlier, may involve encephalopathy, branch retinal
artery occlusion, and sensorineural hearing loss. Callosal T2 hyperintensities
and acutely diffusion-restricting “snowball-like” lesions in the corpus
callosum are highly suggestive of this diagnosis in the right clinical setting
(FIGURE 10-21). Parenchymal, leptomeningeal, and perivascular enhancement
have also been described in Susac syndrome.44,67 The presence of
microhemorrhages, asymmetric white matter T2-hyperintense signal change,
and focal leptomeningeal enhancement is suggestive of cerebral amyloid
angiopathy-related inflammation or amyloid β–related angiitis,
manifestations of an immune reaction to amyloid deposition in the brain
perivascular parenchyma (cerebral amyloid angiopathy-related
inflammation) or vessel walls (amyloid β–related angiitis).63,68 SWI typically
shows microhemorrhages with or without superficial siderosis. In cerebral
amyloid angiopathy-related inflammation, confluent and asymmetric
T2 hyperintensities in cortical and subcortical areas are characteristic,
often extending to the U fibers.68 Focal gadolinium enhancement of the
leptomeninges is frequently seen in amyloid β–related angiitis and may
also be present in cerebral amyloid angiopathy-related inflammation
(FIGURE 10-29).69
Myelitis
Myelitis, or inflammation of the spinal cord, may present acutely over hours,
subacutely over weeks, or in rare cases chronically over months. Suspected
myelopathy based on clinical course and examination findings warrants imaging
FIGURE 10-29
MRI of a patient with probable cerebral amyloid angiopathy associated–related
inflammation. A, Axial T2 fluid-attenuated inversion recovery (FLAIR) MRI showing abnormal
hyperintensity in the left temporal region that is mainly cortical, with nonsuppression of the
sulcal CSF. B, Axial postcontrast T1-weighted MRI showing associated leptomeningeal
contrast enhancement (arrows). C, Axial gradient echo image showing multiple
microhemorrhages (arrows) (these are better visualized on susceptibility-weighted imaging,
but this sequence was not done on this patient).
282 FEBRUARY 2023

to exclude structural compromise and to assess for patterns that might suggest KEY POINTS
the underlying etiology. Spinal MRI is the most sensitive imaging modality to
● Findings of callosal T2
evaluate myelopathy and is essential in ruling out spinal cord compression in the hyperintensities or
acute setting. If MRI is contraindicated, CT myelography can exclude “snowball-like” lesions in
spinal cord compression. PET has poor resolution for spinal cord disorders and is the corpus callosum in the
rarely used as a modality focused on spinal cord pathology; when used to assess context of encephalopathy,
branch retinal artery
for sarcoidosis or neoplasm, both inflammatory and neoplastic pathologies may
occlusion, and hearing loss
be associated with increased spinal cord glucose uptake.70 MRI can help are highly suggestive of
characterize lesions in terms of location (spinal level), rostral-caudal extent Susac syndrome.
(short segment versus longitudinally extensive), transverse extent (transverse
myelitis versus partial myelitis), and topography (eg, hemicord, anterior horn, ● Confluent and
asymmetric T2
posterior column).70-72 The hyperintensities in
pattern of gadolinium cortical and subcortical
enhancement may also provide areas, in association with
clues to diagnosis. Myelitis microhemorrhage on SWI,
are characteristic of
typically manifests as T2 cerebral amyloid
hyperintensity with or without angiopathy-related
cord edema and enhancement. inflammation.
DWI may reveal restricted
● MRI is helpful in
diffusion in spinal cord
determining the length of
infarction. In cases of suspected the lesion (short versus
myelitis with negative MRI longitudinally extensive
initially, repeat MRI should be transverse myelitis), width
(partial versus transverse),
considered because some forms
and location (eccentric,
of myelitis, as well as spinal central, hemicord, anterior
cord infarct, may be associated versus posterior, conus,
with normal MRI early but tracts, or meningeal).
evolve over days.
● The trident sign, which
Short-segment partial has been described in
transverse myelitis is most relation to neurosarcoidosis,
typical of multiple sclerosis. demonstrates
Neurosarcoidosis, NMOSD, leptomeningeal or dorsal
subpial enhancement that
and MOG-associated disorder may or may not involve the
all typically cause central canal.
longitudinally extensive
transverse myelitis. ● Involvement of the conus
medullaris is a clue to myelin
Neurosarcoidosis is
oligodendrocyte
distinguished by a unique glycoprotein-associated
pattern of subpial dorsal disorder as the cause of
enhancement with longitudinally extensive
or without central canal transverse myelitis.
enhancement (trident sign) ● CT of the chest,

(FIGURE 10-30) and may also FIGURE 10-30
abdomen, and pelvis with
Sagittal (A) and axial (B) T2-weighted MRI showing
be associated with meningitis longitudinally extensive spinal cord T2 signal
iodine contrast is a generally
at the base of the brain accepted first method of
change from C1 to T2 (A, double arrow; B, arrow).
screening for occult
(CASE 10-2).73,74 Persistent Sagittal (C, double arrow) and axial (D)
malignancy or systemic
gadolinium enhancement postcontrast T1-weighted MRI showing dorsal
inflammation (eg,
(and to a lesser extent ventral) subpial
on posttreatment MRI enhancement with associated central canal
sarcoidosis).
(often lasting more than enhancement forming the trident sign (D, arrow) in
2 months) is more typical for a patient with probable neurosarcoidosis.

neurosarcoidosis than demyelinating diseases including multiple sclerosis and

NMOSD.75 NMOSD spinal cord lesions are characteristically located centrally
in the cord with varying enhancement patterns and may be associated with
edema or expansion of the cord (FIGURE 10-32); meningeal enhancement is
not typical. Longitudinally extensive transverse myelitis in MOG-associated
CASE 10-2 A 38-year-old woman presented with a 1-month history of headache,

blurred vision in her left eye, low-grade fever of 38.5°C (101.3°F), and
lethargy. Ten days before her admission, she developed back pain,
urinary retention, tingling in her upper and lower extremities, and
abdominal discomfort and was able to ambulate only with assistance.
MRI of the brain and orbits showed left optic sheath enhancement and
leptomeningeal enhancement in the interpeduncular fossa, pons, and
medulla, consistent with basal meningitis. Spinal MRI showed
longitudinally extensive T2 hyperintensity with associated subpial and
central canal enhancement consistent with the trident sign (FIGURE 10-31).
Serum aquaporin-4 IgG and myelin oligodendrocyte glycoprotein (MOG)
IgG were negative. CSF analysis showed low glucose concentration at
31 mg/dL, elevated protein at 126 mg/dL, and lymphocytic pleocytosis
with 159 cells/mm3. Whole-body CT followed by whole-body
fludeoxyglucose positron emission tomography (FDG-PET) did not
identify a hypermetabolic focus. A diagnosis of possible neurosarcoidosis
was made. The patient was treated with methylprednisolone 1000 mg IV
daily for 5 days with complete improvement. She was continued on an
oral prednisone taper over 3 months, as well as maintenance adalimumab
subcutaneous injections.
COMMENT This patient had findings on MRI characteristic of neurosarcoidosis,

including basal meningitis, optic sheath enhancement, and longitudinally
extensive transverse myelitis with meningeal enhancement. The CSF
profile was also supportive of neurosarcoidosis, especially the low
glucose. PET-CT did not reveal any systemic focus for possible biopsy, but
given the highly characteristic imaging pattern, spinal cord biopsy was not
pursued, and she was treated empirically for possible neurosarcoidosis.
284 FEBRUARY 2023

disease should be suspected when a central gray matter pattern manifests as an
H shape on axial T2-weighted MRI or when the conus medullaris is involved
(FIGURE 10-33).76 Although rare, paraneoplastic myelitis may involve specific
spinal cord tracts (dorsal or lateral columns) with long linear segments of T2
hyperintensity and enhancement (TABLE 10-271,77,78).
FIGURE 10-31
Imaging of the patient in CASE 10-2. Axial postcontrast T1-weighted MRI showing
leptomeningeal enhancement in the interpeduncular cistern (A, arrows) and left optic
perineural enhancement (B, arrow). Sagittal (C) and axial (D) postcontrast T1-weighted MRI
showing subpial and central canal enhancement (C, arrows).

FIGURE 10-32
Sagittal (A) and axial (B) thoracic spine T2-weighted FIGURE 10-33
MRI showing longitudinally extensive spinal cord Sagittal (A) and axial (B) thoracic spine
signal change and edema in all visualized levels T2-weighted MRI showing patchy
(B, arrow). Sagittal (C) and axial (D) postcontrast longitudinally extensive cord signal change
T1-weighted MRI showing parenchymal rim involving the conus medullaris (A, double arrow
enhancement (D, arrow) in a patient with for the longitudinal segment, short arrows
aquaporin-4 IgG positive neuromyelitis optica demonstrating patchy short segments; B,
spectrum disorder. arrow). Sagittal (C) and axial
(D) postcontrast T1-weighted MRI showing
nodular parenchymal enhancement (C, double
arrow, arrows; D, arrow) in a patient with
myelin oligodendrocyte glycoprotein
IgG–associated disease.
EXTRANEURAL IMAGING MODALITIES IN AUTOIMMUNE NEUROLOGY

CT of the chest, abdomen, and pelvis with iodine contrast is useful for screening
when an occult malignancy or systemic etiology such as sarcoidosis is suspected.
It has the advantage of being readily available at most centers and providing good
spatial resolution. FDG-PET of the whole body may be useful in detecting smaller
occult malignancies or foci of inflammation in patients with negative body CT
screen; in some centers, PET is combined with CT as first-line screening. In some
cases, including FDG-PET of the brain with the body is appropriate, especially when
an autoimmune or paraneoplastic encephalitis is suspected but MRI is negative.
When the neurologic syndrome is suggestive of or proven to be
paraneoplastic in origin and tumors of the ovaries or testicles are suspected,
286 FEBRUARY 2023

ultrasonography is preferred over CT for screening. When suspicion for these
malignancies is high (eg, in the setting of NMDA receptor encephalitis), a
transvaginal approach for ovarian assessment is more sensitive than
pelvic ultrasound.79
CONCLUSION
Neuroimaging is essential in the evaluation of patients with inflammatory,
autoimmune, and paraneoplastic neurologic disorders. Familiarity with the
Imaging Patterns in Myelitisa TABLE 10-2
Disorder >Size Most common MRI characteristics

Multiple sclerosis Small and ovoid, lesions may become Eccentric “partial myelitis,” enhancement is either
confluent in progressive forms homogenous or ringlike
Neuromyelitis optica Longitudinally extensive transverse Central “bright and spotty” T2 lesions, present
myelitis (LETM), may be short segment cord edema and may be hypointense on
T1-weighted MRI, enhancement may be ringlike in
one-third of cases77
Myelin oligodendrocyte LETM, may be short segment Can involve the conus medullaris, lesions are often
glycoprotein—IgG restricted to the gray matter on T2-weighted MRI
associated myelitis (the H sign), enhancement is faint and patchy
Parainfectious and idiopathic Variable, may be LETM in the setting of Nonspecific, can be limited to the gray matter on
acute disseminated encephalomyelitis T2-weighted MRI in acute flaccid myelitis (the H
(ADEM) sign)
Neurosarcoidosis LETM Pial enhancement, typically dorsal, may cause the

trident sign appearance with central canal
involvement on axial postcontrast T1-weighted MRI
In the setting of Variable Systemic lupus erythematosus (SLE): typically

rheumatologic disorders associated with NMOSD but may be associated
with SLE flares in the setting of negative
aquaporin-4 IgG
Behçet myelitis: can cause a distinctive hyperintense
rim with hypointense core on T2-weighted MRI (the
bagel sign); the motor neuron sign was also
described, affecting just the anterior horn cells
symmetrically13
Sjögren myelitis: typically associated with NMOSD
but may occur in the setting of negative
aquaporin-4 IgG
Paraneoplastic Usually LETM May involve gray matter or a tractopathy on

T2-weighted MRI (ie, myelopathies associated
with amphiphysin and collapsin response
mediator protein-5 [CRMP5] antibodies)78
Anti–glial fibrillary acidic Usually LETM Central thin linear enhancement along the central
protein (GFAP) canal on sagittal postcontrast T1-weighted MRI
IgG = immunoglobulin G; MRI = magnetic resonance imaging.

a
Modified with permission from Abdel-Wahed L, Cho TA, Semin Neurol.71 © 2021 Thieme.

specific findings on imaging modalities, appropriate yield, and expected

changes with treatment are important in differentiating the underlying
inflammatory etiologies. Given the incomplete sensitivity and delay in result
reporting for neuronal autoantibody testing, neuroimaging may allow empiric
treatment in the right clinical setting, resulting in potential avoidance of
long-term morbidity.
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DISCLOSURE
Continued from page 255 health care. The institution of an immediate family
member of Dr Cho has received research support
National Institutes of Health and has received from the National Institutes of Health.
publishing royalties from a publication relating to

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Imaging of Central REVIEW ARTICLE

ESSENTIAL POINTS: Knowledge of imaging modalities, both structural and

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MRI IN NEUROINFLAMMATORY DISEASE

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activity in inflamed or hyperactive neuronal tissue (status epilepticus) or ● When assessing

SYNDROMIC APPROACH TO IMAGING ● Trauma or neurosurgery

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showed leptomeningeal enhancement with approximately one-quarter of those

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to adjacent orbital, sinus, and hypothalamopituitary tissues. Dural lesions in

262 FEBRUARY 2023

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● IgG4-related disease (as

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KEY POINTS present with subacute (over 6 to

264 FEBRUARY 2023

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266 FEBRUARY 2023

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Lesions are usually isointense or hypointense lesions on T1-weighted imaging with

MULTIPLE AND CONFLUENT CORTICAL AND SUBCORTICAL DISEASE. Multiple and

INVOLVEMENT OF DEEP GRAY MATTER. Involvement of the deep gray matter in

268 FEBRUARY 2023

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● Multiple and confluent

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heralding an occult small cell lung cancer. Cases of extensive T2-hyperintense

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CASE 10-1 A 23-year-old woman developed headache and confusion followed by

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Characteristics Inflammatory differential diagnosis Noninflammatory differential diagnosis

Topography and size of lesion

Well-defined, peripheral, and ovoid, Multiple sclerosis Ischemic infarcts

Circumventricular lesion (abutting third Neuromyelitis optica Not applicable (NA)

Space-occupying lesion Tumefactive demyelination, central Glioma

Brainstem atrophy Chronic multiple sclerosis or NMOSD, Neurodegenerative causes such as

Punctate and curvilinear CLIPPERS, Susac syndrome NA

Nodular Neurosarcoidosis, CNS vasculitis NA

Open ring CNS demyelination NA

Meningeal and cranial neuropathies Neurosarcoidosis, IgG4-related Tuberculosis meningitis, Lyme

Diffusion restriction Acute demyelination, neuro-Behçet Lymphoma, abscess, acute ischemia,

Microhemorrhages on Inflammatory cerebral amyloid HSV encephalitis

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sensorineural hearing loss. It may involve the brainstem with punctate

274 FEBRUARY 2023