Neuromyelitis optica:
NMO was first described by Dr.
T.C.
Allbutt in 1870s and subsequently by Dr.
Eugène Devic in 1894 as a monophasic disease characterized by both severe bilateral optic neuritis and transverse myelitis(TM).[1,5] Later studies showed that NMO is often relapsing rather than a monophasic disorder and authors then considered NMO to be a variant of multiple sclerosis.[1] However with further advances in the past decade initiated by the discovery of the disease-specific autoantibody,
NMO–immunoglobulin G (NMO-IgG),
and subsequent identification of the main target autoantigen,
aquaporin-4 (AQP4) in 2004 has helped us distinguish NMO as a distinct disease from multiple sclerosis (MS).[1,2,4]
Diagnostic criteria:
In 1999,
Wingerchuk et al.
first proposed diagnostic criteria for identification of NMO which consisted of absolute criteria and supportive criteria [6] which was later revised in 2006.
The revised NMO criteria [8] eliminated the restricted involvement of the spinal cord and optic nerves and emphasized the specificity of AQP4-IgG–seropositive status for identification of NMO.[1,8] It consisted of:[3,7]
Absolute criteria: Optic neuritis + Acute myelitis
Supportive criteria: At least 2 of the following:
(a) Spinal cord lesion > 3 vertebral segments
(b) Brain MRI not diagnostic for MS
(c) AQP4- IgG +
In 2007 with recognition of new clinical and radiologic manifestations in AQP4-IgG–seropositive patients the term NMO spectrum disorder(NMOSD) was used which encompasses anti-AQP4 antibody seropositive patients with limited or inaugural forms of NMO and with specific brain abnormalities.
It also includes anti-AQP4 antibody seropositive patients with other autoimmune disorders.[2]
The International Panel for NMO Diagnosis (IPND) in 2015 updated the diagnostic criteria,
thereby markedly improving the diagnosis of NMOSD.[8]
It stratified patients according to AQP4-IgG status as follows: (a) seropositive patients and (b) seronegative patients or those with unspecified serologic status.
Fig. 1: Table 1: 2015 IPND Criteria for NMOSD
References: Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-89.
Epidemiology:
Incidence is 0.053 to 0.40 per 100,000 population and age of onset 32-45 years.
NMOSD characteristically shows a high female predominance from 9:1 to 3:1.[5]
Clinical features: In table 1
MRI features:
Optic neuritis:
Characteristic findings of bilateral and longitudinally extensive optic nerve involvement,
usually affecting more than half the length of the optic nerve and a trend to involve the posterior optic pathway with extension to the chiasm and optic tract is commonly seen in NMOSD.[1,2]
Thickened optic nerve with hyperintensity on T2-weighted images and enhancement on gadolinium-enhanced T1-weighted images is seen in acute stage while atrophy of the optic nerves and variable hyperintensity on T2-weighted images is seen in chronic stage.[1,2]
Fig. 2: Optic neuritis in NMO
Spinal cord:
The most distinct manifestation of NMO is longitudinally extensive transverse myelitis (LETM) defined as a lesion that spans over 3 or more contiguous vertebral segments and predominantly involves central gray matter on the spinal cord MRI.[1,2] This is due to the fact that grey matter's cell adjacent to the ependymal cells of the central canal are rich in aquaporin 4.[1,2] Cervical and the upper thoracic spinal cord segments are more frequently involved than the lower thoracic and lumbar regions.[1,2]
LETM appears as hyperintensity on T2-weighted sequences and hypointensity on T1-weighted sequences involving the central gray matter which shows enhancement on post contrast images.[1,2]
Fig. 3: LETM in NMO
Brain lesions:
Prevalence of brain lesions is variable,
occurring in 24%–89% of NMOSD patients with most of the lesions being unspecific and clinically silent.[1] Lesions occur in areas where there is expression of AQP4 in the brain,
the subpial regions,
periependymal regions,
circumventricular organs,
brainstem,
chiasm/hypothalamus,
and corpus callosum.[1,2]
Periependymal lesions are seen in the diencephalic area surrounding the third ventricle,
dorsal brainstem surrounding the fourth ventricle and perependymal area surrounding the lateral ventricles.[1,2]
Corpus callosum is typically involved at its ependymal surface,
with the involvement often affecting most of its length.
In acute phases,
edematous and heterogeneous hyperintensity on FLAIR and T2W images is seen giving a typical marbled pattern.[1,2]
Hemispheric white matter lesions are extensive and confluent and often tumefactive (>3 cm in longest diameter) or have long spindle-like or radial-shape following white matter tracts.[2]
Corticospinal tract involvement is seen in 23-44% of patients with the lesions being unilateral or bilateral,
and extending from the deep white matter in the cerebral hemisphere through the posterior limb of the internal capsule to reach the cerebral peduncles of the midbrain or the pons. These lesions are contiguous and often longitudinally extensive,
following the pyramidal tracts.[1,2]
Fig. 4: Diencephalic and cerebral lesions in NMOSD
References: Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-89.
Multiple Sclerosis
It is a chronic,
relapsing inflammatory neurological disease characterized by demyelination,
axonal injury and gliosis within the brain and spinal cord.[9,10]
Characteristically,
and by definition,
multiple sclerosis is disseminated not only in space (i.e multiple lesions in different regions of the brain) but also in time (i.e.
lesions occur at different times).[9,10]
A number of patterns of longitudinal disease have been described:
1.
Relapsing-remitting:
o most common (70% of cases)
o patients exhibit periodic symptoms with complete recovery (early on).
2.
Secondary progressive:
o approximately 85% of patients with relapsing-remitting MS eventually enter a secondary progressive phase
3.
Primary progressive
o uncommon (10% of cases)
o patients do not have remissions,
with neurological deterioration being relentless
4.
Progressive with relapses
5.
Benign multiple sclerosis
o 15-50% of cases
o defined as patients who remain functionally active for over 15 years
Diagnostic criteria:
McDonald diagnostic criteria is a clinical,
radiographic,
and laboratory criteria used in the diagnosis of multiple sclerosis.
It were originally introduced in 2001 revised in 2005,
2010,
2016 (by MAGNIMS) and most recently in 2017.
Fig. 5: 2017 McDonald Criteria for the Diagnosis of Multiple Sclerosis
References: Bradshaw, Michael & Houtchens, Maria. (2018). Neurology Board Review: Multiple Sclerosis.
Epidemiology: Incidence is 3.6 cases per 100,000 population and age at onset is 20-50 years.[5] There is strong,
female predilection with a F:M ratio of approximately 2:1.[5]
Clinical features:
Clinical presentation is both highly variable acutely,
as a result of varying plaque location,
as well as over time
Imaging features:
Optic neuritis:
It is typically unilateral and involves a shorter segment of the optic nerve with less extension to the chiasm than in NMOSD.[9,10]
Optic nerve thickening,
short segment hyperintensity on T2W images,
and variable enhancement on T1W images are characteristic MRI findings of acute phase.[9,10]
Spinal cord:
Myelitis in multiple sclerosis has smaller longitudinal extension (one or two vertebral bodies) and a more peripheral distribution in the spinal cord (white matter involvement),
which is seen on axial images as dorsal or lateral lesions in the spinal cord.
The cervical spine is the most commonly affected segment with variable patchy,
nodular,
or ring-shaped enhancement in acute phases.[9,10]
Fig. 6: Spinal cord lesion in MS
Brain lesions:
Corpus callosum: Inferior part of the corpus callosum,
referred to as the callosal-septal interface,
is usually affected by small ovoid lesions that characteristically appear hyperintense on FLAIR and T2-weighted images with variable enhancement on T1-weighted images in the acute phase.[9,10]
Periventricular lesions or Dawson fingers: They are ovoid and perpendicular lesions relative to the lateral ventricle surface that are arranged around the medullary veins.
The presence of Dawson finger–type lesions,
the coexistence of at least one lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe,
and the presence of a juxtacortical U-fiber lesion are important features for distinguishing multiple sclerosis from NMOSD.[9,10] Cortical/juxtacortical lesions and widespread cortical atrophy is more commonly seen in multiple sclerosis.
Infratentorial Lesions: Brainstem lesions primarily involves the pons,
middle cerebellar peduncle,
and cerebellar white matter.
Moreover,
abnormal signal intensity in the intrapontine trigeminal nerve fibers is an additional imaging feature that helps differentiate multiple sclerosis from NMOSD.
In acute phases,
enhancement seen in usually nodular or ring like in contrast to the one see in NMOSD.[9,10]
Corticospinal Tract.—Rarely focal lesions can involve the corticospinal tract.
Multiple sclerosis lesions are usually smaller than NMOSD lesions because there is less vasogenic edema involved.[9,10]
Fig. 7: Brain lesions in MS
Differential diagnosis of MS from NMOSD is critically important because disease modifying treatment for MS,
such as interferon-β,
fingolimod,
natalizumab and alemtuzumab are inefficacious in or may aggravate NMOSD.[5]
Differentiation of NMO and MS is outlined for quick radiological review.
Fig. 8: Differentiation of NMO and MS